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Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation and anti-inflammatory drugs

Sunishtha Kalra, Rohit Malik, Govind Singh and 6 more

Inflammopharmacology · 2022 · Review · CC BY

doi:10.1007/s10787-022-01017-8

Abstract

Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, and assaults. During the past decade, an abundance of new evidence highlighted the importance of inflammation in the secondary damage response that contributes to neurodegenerative and neurological deficits after TBI. It results in disruption of the blood–brain barrier (BBB) and initiates the release of macrophages, neutrophils, and lymphocytes at the injury site. A growing number of researchers have discovered various signalling pathways associated with the initiation and progression of inflammation. Targeting different signalling pathways (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-β1, and NLRP3) helps in the development of novel anti-inflammatory drugs in the management of TBI. Several synthetic and herbal drugs with both anti-inflammatory and neuroprotective potential showed effective results. This review summarizes different signalling pathways, associated pathologies, inflammatory mediators, pharmacological potential, current status, and challenges with anti-inflammatory drugs.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 21, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Traumatic brain injury (TBI) is identified as an important global health concern which represents a leading cause of death and disability. TBI occurs due to direct impact or hit on head, caused by a number of things including motor vehicles, crushes, and assaults. The result of initial mechanical damage that happens at the time of injury is referred to as a primary injury. Primary injury is responsible for initiation of secondary injury. Secondary injury develops over a periods of time after primary injury (Hovda et al.; Xiong et al.; Singh et al. ). Secondary injury cascades including oxidative stress, endoplasmic reticulum stress, and neuroinflammation contribute to long-term brain damage and can be triggered by a variety of risk factors. These damage cascades converge on an early tau acetylation route, which may act as a catalyst for subsequent degeneration (Lucke-wold et al. ). Onset of secondary injury is a result of physiological and biochemical cascades that finally leads to neuronal cell death and functional impairments. Primary injury is an irreversible approach because it is refractory to most therapeutic strategies. It is only prevented by use of safety devices (Werner and Engelhard; Mbye et al. ). The interval during which secondary injury develops gives a golden chance for medical approaches that has the ability to prevent and reduce secondary harm while also improving long-term clinical outcomes. However, significant preclinical findings have yet to be validated in clinical trials. Clinical trials have failed due to the physiological variability of trauma patients, as well as a lack of comprehensive pharmacokinetic study for determining the best dosage, starting time of therapy, and therapeutic period of the target drugs (Schouten ). As a result, understanding of various molecular and cellular factors which leads to secondary injury is necessary for developing successful neuroprotective approaches for TBI. Neuroinflammation is a secondary damage response that contributes to neurodegenerative and neurological deficits after a TBI. Although most researchers have highlighted negative neuroinflammatory consequences on damaged brain, significant benefits can be obtained if neuroinflammation is treated in a controlled manner. We will look at synthetic and herbal anti-inflammatory drugs that have been explored as therapeutic options for TBI and have shown potential in clinical trials.

Neuroinflammation in pathogenesis of TBI

Neuroinflammation plays an important role in neurological impairments and neurodegeneration that might occur after TBI. Increased levels of inflammatory mediators, glial cell activation, and leukocyte recruitment are signs of post-traumatic neuroinflammation (Morganti-Kossmann et al. ).

TBI results in disruption of BBB, initiate release of macrophages, neutrophils, and lymphocyte at site of injury. Researchers, working on TBI in animals and humans, have observed an increase in blood-borne immune cells inside the brain parenchyma. Inflammatory mediators are released by these cells, which attract immune and glia cells to the injured area. In addition to immune cell invasion, resident microglia activation plays an important role in damage. Microglial processes form a first-line defence barrier between healthy and injured area of brain (Davalos et al.; Haynes et al. ). Whenever microglia become excessively reactive or activated, they release oxidative metabolites (e.g. nitric oxide and reactive oxygen species) as well as pro-inflammatory cytokines [e.g. tumour necrosis factor α (TNF-α), interleukin (IL-1β), and interferon γ (IFN-γ)] that have a detrimental impact on neurons (Block and Hong ). Furthermore, production of pro-inflammatory cytokines and supplementary components determines the successive stimulation of astrocytes and glial scar formation in brain injury. Development of intermediary filaments (GFAP and vimentin), elevated cellular accumulation, and cell swelling are all signs of astrocyte activation (Herrmann et al. ).

Corresponding to microglia, reactive astrocytes also produce destructive as well as neuroprotective effects in TBI. Activation of astrocyte stimulates variety of neurotrophic factors like brain-derived neurotrophic factor (BDNF) to protect and support brain from cellular death persuaded by injury (Zhao et al. ). Moreover, astrocytes are important regulators of extracellular glutamate level and responsible for reducing glutamate excitotoxicity in neurons as well as neuroglia (Schousboe and Waagepetersen ). Particularly, damaged astrocytes aggravate transgenic depletion and neuronal deterioration of reactive astrocyte which consequently promotes neuronal death and assists terrible consequences following TBI (Maeda et al. ). Hypertrophic astrocytes around lesion site after damage form a suppressive extracellular matrix containing chondroitin sulphate proteoglycans, which prompt the formation of glial scar. The developed strong physiochemical barrier restricts functional connections needed for axonal repair and growth, as well as impedes axonal regeneration (Cafferty et al. ). Contrarily, astrocytes give nutritional guidance and support throughout axonal growth after neuronal injury, but chronic astrogliosis limits and impairs functional recovery and axon regeneration (Menet et al.; Wilhelmsson ).

Inflammatory signalling pathways in pathogenesis of TBI

Nuclear factor-kappa B (NF-κB) NF-kB is an imperative inflammatory signalling pathway which involves in the synthesis of inflammatory molecules and pro-inflammatory genes such as cytokines and chemokines (Liu et al. ). NF-kB is a downstream element for the stimulation of various receptors such as toll-like receptor 4 (TLR-4) and tumour necrosis factor receptor-associated factor6 (TRAF-6) in human and animals which suffered with TBI. As a consequence, inhibiting NF-kB reduces apoptosis and inflammation following injury. A previous study reported that NF-kB activation in glial and neuronal cells is associated with neuroprotective activity and neurodegenerative diseases (Singh and Singh ).In glial cells, NF-kB promotes inflammation, whereas in neurons it plays a role in synaptic plasticity, neuronal development, survival, and synaptic plasticity (Mattson and Camandola ). NF-kB levels were found to be higher in rats following fluid percussion and controlled cortical impact head injury, and also in biopsies of human contused neural tissue (Yang et al.; McKeating and Andrews ).

Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) Pathway JAK/STAT pathway is the fundamental channel intended for transmission of growth factors and cytokines accountable for variety of biochemical processes including axon regeneration, inflammation, cell differentiation, proliferation, and death (Oliva et al. ). Activation of JAK-STAT pathway commenced with a particular ligand binding to receptor on cellular surface, which subsequently triggers internal transmission via JAK kinase recruitment. JAK triggers dimerization and expression of STAT components. Some STAT proteins are found in nucleus and regulate gene expression by binding to a specific DNA sequence. After TBI, inflammatory process decreases JAK/STAT expression, resulting in increased cell death in cortical pericontusional region (Oliva et al. ). After TBI, rat peri-injured cortex cells were treated with recombinant erythropoietin (rhEPO), which increased JAK2 and STAT3 phosphorylation and reduced apoptosis. The JAK2 inhibitor AG490 lowered pJAK2 and pSTAT3 levels while increasing mRNA expression of many apoptosis-associated genes, implying that JAK2-STAT3 pathway is activated (Zhao et al. ) (Table 1).

Mitogen-Activated Protein Kinase (MAPK) Pathway MAPK is a threonine/serine-dependent protein kinase which is triggered by phosphorylation in response to diverse cells trauma. It is important for cell differentiation, proliferation, and survival. Cascades are made up of c-Jun NH (2)-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38. Numerous studies reported that activation of p38 and JNK pathway elevates neuronal damage accompanying spinal cord injury and cerebral ischemia (Otani et al. ). Following TBI, cell line-based studies revealed astroglial growth and fast ERK activation (Carbonell and Mandell ). Pathophysiology of TBI includes abnormalities in the MAPK signalling pathway and studies revealed that blocking this cascade improved cell survival rate and significantly reduces intensity of cortical lesions. JNKs are stress stimulated protein kinases that are found in nucleus of neuronal cells and are linked to neurodegeneration. TBI can activate JNK and cause a complex cascade in mitochondria of brain cells, resulting in apoptosis (Chi et al.; Dietrich and Bramlett ) (Fig. 1).

PI3K/Akt/mTOR Signalling Pathway During brain development, the PI3K/Akt/mTOR signalling cascade is an important regulator of neuronal cell proliferation, axon outgrowth, and dendritic formation (Kumar ). Various hormones and growth factors that affect mTOR complex and target molecules like mTORC1 and mTORC2 induce downstream Akt and activation of PI3K (Dibble and Cantley ). mTOR integrates input from various upstream signals to control cell death, cell growth inhibition, and autophagy. mTOR regulates synthesis of proteins in axons and cell bodies, which are necessary for cell development. TBI-associated symptoms like inflammatory reactions and epilepsy are mostly controlled by inhibiting mTOR pathway (Guo et al. ).

Glycogen synthase kinase 3 (GSK-3) Pathway GSK-3 controls protein synthesis, microtubule dynamics, glycogen metabolism, cell differentiation apoptosis, and cell death. Wnt and Akt are two important signalling pathways that regulate GSK-3β activity and are also known as protein kinase B (Fang et al. ). Due to Akt activation, phosphorylation of GSK-3β induces response of pro and anti-inflammatory in monocytes. Exclusive GSK-3βinhibitors provide protection to cells from proapoptotic stimulant depending on the role of GSK-3β in apoptosis. Irregular stimulation of GSK-3β is associated with chronic neuroinflammation and neurodegeneration. Several researches have shown that GSK-3β has a role in TBI models of neuroinflammation and also showed the potency of numerous inhibitors of GSK-3βin TBI (Li et al.; Llorens-Marítin et al. ).

Nuclear Factor Erythroid 2-Related Factor 2 Pathway Nrf2 is a gene transcription component which protects cells from a variety of damaging stimuli. Nrf2 is mostly found in the cytoplasm, attached to its inhibitor Keap1, which restricts Nrf2 from entering the nucleus. In a recent study, it was found that Nrf2 downregulation promotes neuronal death and neuroinflammation by increasing oxidative stress, TGF-β1, NF-kB, and MMP3/9 (Suzuki and Yamamoto ).

Rho-GTPase Pathway Rho-GTPases (Cdc42, Rac1, and RhoA) are principal regulators of cell adhesion and cytoskeletal and cell adhesion controlling a wide order of cellular processes (Chi et al. ). Rho GTPase signalling dysregulation has been associated with aetiology of amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease (Mulherkar and Tolias ). Continuous over expression of functional RhoA degrades neuritis repair and axonal regeneration following TBI, since it inhibits axonal regeneration as well as apoptotic responses. Astrocyte activation and proliferation are common responses to CNS damage (Mulherkar and Tolias ). The progressive formation of a scar-like structure by astrocytes, oligodendrocytes, microglia fibroblasts, and meningeal cells limits axonal regeneration and slows TBI recovery. In lateral fluid percussion injury model, RhoA activation has been observed in ipsilateral brain of rat (Dubreuil et al. ). Furthermore, it was also observed that RhoA activity was increased in neuroglia and spinal cord of rats and mice in rodent models of spinal cord injury models (Wu and Xu ).

TGF-β1 Signalling Pathway Microglial inactivation is characterized by TGF-β signalling. TGF-β1 has been shown to play a protective role in CNS diseases in previous research. Taylor et al. discovered that this pathway enhanced functional improvement after intracerebral haemorrhage by altering microglial cell alternative stimulation (Taylor et al. ).

Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) Pathway It is a multi-protein complex which aggregates and activates caspase-1 in response to hazardous stimuli and promotes release of the pro-inflammatory cytokines IL-1β and IL-18. Following TBI, immune system activated by these cytokines produces neuroinflammation that contributes to cell death (Lamkanfi et al. ).

Anti-inflammatory drugs and TBI

Glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) are primarily commercially available synthetic anti-inflammatory drugs. Glucocorticoids have potent immunosuppressive and anti-inflammatory properties. They suppress preliminary signs of inflammation like redness, discomfort, and swelling as well as the later stages of wound healing and its proliferative processes that occur in chronic inflammation. Indeed, steroids bind to certain intracellular receptors, forming a complex that later on modulates gene expression, inducing some proteins to be synthesized while others are inhibited (Barnes and Adcock ).Glucocorticoids also interact with AP-1, a heterodimer of Fos and Jun proteins that acts as a transcription factor activator. Inhibition of AP-1 inhibits the activity of leukocytes, lymphocytes, and mononuclear cells, as well as the release of pro-inflammatory cytokines including TNF-α and IL-2. Steroids also suppress COX-2 expression, a gene that is ordinarily activated by inflammatory mediators and produces inflammatory prostanoids. In addition, they prevent osteocalcin production in osteoblasts stimulated by vitamin D3. Also, steroids alter collagenase expression and diminish the production of lipocortin 1 (Barnes and Adcock ).

NSAID is a class of drugs having combined analgesic, antipyretic, and anti-inflammatory actions due to their inhibitory effect against cyclooxygenase (COX) enzyme. This COX inhibition remarkably reduces the level of IL-1β and also impedes IL-6 synthesis by modulating vasodilator prostaglandin synthesis pathways. Moreover, NSAIDs also inhibit calcium-dependent glutamate release which consequently attenuates glutamate-induced neurotoxicity Breitner ).

Most importantly, certain NSAIDs (e.g. aspirin, naproxen, ibuprofen, diclofenac, nabumetone, oxaprozin, and sulindac) also impede COX-1 enzyme causing unwanted adverse effects. However, novel compounds, on the other hand, work selectively on COX-2 and are thought to be more effective. Celecoxib and rofecoxib, two novel anti-inflammatory medicines, are designed to target inflammatory sites alongside protecting non-inflamed areas where COX-mediated prostaglandin generation may be advantageous (Leveugle and Fillit; Lehmann et al.; Ricote et al. ).

Another aspect of NSAIDs is that they stimulate the proliferator-activated receptor (PPAR), which causes transcriptional regulatory effects that decrease a variety of pro-inflammatory chemicals and microglial activity. Furthermore, several NSAIDs have antioxidant properties and inhibit NF-kB activation (Grilli et al. ) (Table 2).

Anti-inflammatory herbal drugs and TBI

Both crude plant extracts and their isolated compounds have shown neuroprotective effects on nerve functions due to their anti-inflammatory and antioxidant properties. Plant extracts used in traditional system for the alleviation of pain, fever, and inflammation have found to contain several natural anti-inflammatory medicines. A few of these natural products’ processes have been partially explored in recent years, and they are currently considered for therapy of chronic inflammatory and neurodegenerative illnesses. The majority of these medicines work by suppressing COX-2 transcription instead of activity. They also inhibit the expression of a number of pro-inflammatory genes (Keshavarzi et al. ).

Recently, numbers of traditional supplements and herbal medicine have been studied in treatment of TBI. Both animal and cellular TBI models revealed elevated expression of NF-κB, TNF-α, IL-6, and IL-1.Treatment with osthol, a coumarin derivative derived from Cnidium monnieri, reduced inflammatory mediators and enhanced neurological functions alongside elevating the neuronal count surrounding the injured area. Furthermore, treatment with osthol lowered the production of numerous inflammatory mediators (Kong et al. ).

We evaluated previous study to analyse possible neuroprotective effect of several medicinal plants in brain injury, owing to the increasing number of research published in recent years. Medicinal plants included in Table 3 have shown pharmacological potential in different model of TBI.

Anti-inflammatory drugs and neuroprotective potential in TBI

Anti-inflammatory approaches to prevent and treat neurotoxicity-associated neurological diseases have proved effective in vast cell-based and pre-clinical models, although nothing has been confirmed in later stages of clinical evaluations. However, with conclusive experiments this therapeutic approach propounds encouraging prospects for clinical exploration. In experimental animal models of stroke, both glucocorticoids and general anaesthetic drugs have sparked a great attention in neuroprotection; however, this has yet to be proved in humans (Degos et al. ). At some stage of stroke, head trauma, and meningeal bleeding, glucocorticoids have been, however, reported to be ineffective. Classic hypnotics such as thiopental and midazolam have immune-modulating properties and can reduce inflammatory responses in the peripheral nervous system. In an experimental mouse model, they suppress chemotaxis, neutrophil adherence, and phagocytosis as well as impede the discharge of free radicals and pro-inflammatory cytokines; however, these activities have yet to be proven in humans. COX inhibitors (mainly nimesulide and indomethacin) exhibit neuroprotective activity in neonatal mice with brain lesions (Muller ). The communication repression between the brain and activated peripheral inflammatory cells through blood–brain barrier induces neuroprotective action. Moreover, COX inhibitors are also reported remarkably effective against depression and various other psychiatric disorders. Noteworthy, celecoxib has been affirmed as an effective drug to treat serious depression and schizophrenia, predominantly in the early stages. Furthermore, acetyl salicylic acid has demonstrated preventative and curative effect against schizophrenia (Degos et al.; Muller ).

Current status of anti-inflammatory drugs in management of TBI

Despite advancements in preventative, diagnostic, and surgical techniques, therapeutic choices have been limited for management of TBI. Till date, no pharmacological remedy has been found to provide neuroprotective effects by targeting secondary damage mechanisms (Lozano et al. ).

Rehabilitation therapy is used in the majority of the patients. Because damage caused by initial injury is nearly impossible to treat, the rational approach for therapy intervention that provides clinically relevant advantages is to prevent subsequent cell death. It provides a large treatment window due to a delay in harm caused by secondary cell death (Lozano et al. ). Targeting neuroinflammation among the secondary wave of biochemical pathways appealed to this extended time for intervention beginning. A variety of medications have been examined and reported to decrease inflammation in animals and TBI patients at the preclinical and clinical levels.

A systematic analysis was performed through US National Institutes of Health clinical trials database using various search strategy consisting of either single or combination of the following keywords: traumatic brain injury, anti-inflammatory drugs, COX-1, COX-2, and specific names of distinct anti-inflammatory drug such as aspirin, celecoxib, ibuprofen, diclofenac. However, no specific findings are obtained in relevance to intervention of anti-inflammatory drugs in prognosis of traumatic brain injury. Although the use of dexamethasone in prognosis of TBI patients with brain contusions and pericontusional oedema is under recruiting status of phase 3, hopefully it will give expected outcomes.

Some clinical evidences suggested certain clinically approved drugs having potential anti-inflammatory activity are used in the treatment of TBI and some are under clinical trials as mentioned in Table 4. Meta-analysis study by Begemann et al. affirms that TBI patients receiving progesterone, erythropoietin, or cyclosporine have higher chance of a favourable outcome comparatively to those receiving placebo.

Challenges with anti-inflammatory drugs

Clinical trials including anti-inflammatory drugs have produced mixed outcomes so far. Nonselective COX inhibition, inadequate use of specific anti-inflammatory medicines for a given illness or illness progression/severity, sub-optimal dosing at specified location, or inadequate transmission through BBB to brain could all be reasons for varied outcomes (Gilgun-Sherki et al. ).

Long-term use of high-dose NSAIDs has been linked to the development of autoimmune disorders. The use of NSAIDs in TBI models is currently investigated; however, the results have been equivocal thus far. In a pre-clinical study, chronic ibuprofen treatment significantly increased cognitive and histological outcome. However, it failed to provide neuroprotection in a TBI model (Harrison et al. ).

Prolonged administration of ibuprofen in injured animals provides a much lower results as compared to placebo. Moreover, no significant differences in tissue atrophy level in hippocampus or cortex between treated and untreated mice were observed. These data imply that using high dosages of anti-inflammatory drugs for an extended length of time after trauma may diminish the neuroprotective effects of post-traumatic inflammatory cytokines (Harrison et al. ).

Summary

Multiple studies in animal models of TBI have shown that neuroprotective therapies can reduce subsequent damage processes and/or enhance behavioural outcomes. However, none of these promising experimental neuroprotective treatments have been translated to improve clinical outcomes in human. As a result, the development of new anti-inflammatory medications for the treatment of neurodegenerative illnesses that are based on improved BBB transit and have a higher safety profile could result in beneficial therapy. Moreover, the heterogeneity of population genetics and the degree of pathology should be considered while developing novel anti-inflammatory medications. To truly understand the process and chemistry of anti-inflammatory drug delivery into the brain, more research is required. Hence, to decrease this native risk, more specific methods are required to modulate the inflammation. Inflammasome inhibition will be one approach. This technique, however, remains difficult due to a lack of or insufficient understanding of inflammasome structure and activation. Nonetheless, some research on psychiatric disorders has focused at inhibiting NLRP3, the best studied inflammasome. This antagonist endogenously formed after brain injury, and it reduces lesions size in animal models when administered systemically or intracerebrally. To conclude, neuroprotection strategies based on inflammation modulation must maintain the immunological defense and curative functions of inflammation along with eliminating its neurotoxic effects; as a result, three major anti-inflammatory approaches for the neuroprotection pathway can be evolved: modification of peripheral inflammation-CNS communication, modification of pro-inflammatory cytokines–intracerebral targets interaction, and modification of inflammasome production in brain cells.

References 115

  1. 1.

    (2022) In: Academicjournals.org. https://academicjournals.org/article/article1380714402_Wang.pdf. Accessed 18 Apr 2022

    Not in our library

  2. 2.

    (2022) In: Gpb.sav.sk. http://www.gpb.sav.sk/2002_03_231.pdf. Accessed 18 Apr 2022

    Not in our library

  3. 3.
    Comparison of the effects of erythropoietin and anakinra on functional recovery and gene expression in a traumatic brain injury model · 2013
    Not checked
  4. 4.

    Baez-Jurado E, Vega G, Aliev G, Tarasov V, Esquinas P, Echeverria V, Barreto G. Blockade of neuroglobin reduces protection of conditioned medium from human mesenchymal stem cells in human astrocyte model (T98G) under a scratch assay. Mol Neurobiol. 2017;55:2285-2300.

    Not in our library10.1007/s12035-017-0481-y

  5. 5.

    Barnes PJ, Adcock I. Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci. 1993;14(12):436-41.

    Not in our library10.1016/0165-6147(93)90184-l

  6. 6.

    Baratz R, Tweedie D, Rubovitch V, Luo W, Yoon J, Hoffer B, Greig N, Pick C. Tumor necrosis factor-α synthesis inhibitor, 3,6′-dithiothalidomide, reverses behavioral impairments induced by minimal traumatic brain injury in mice. J Neurochem. 2011;118:1032-1042.

    Not in our library10.1111/j.1471-4159.2011.07377.x

  7. 7.

    Basu A, Krady J, O'Malley M, Styren S, DeKosky S, Levison S. The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. J Neurosci. 2002;22:6071-6082.

    Not in our library10.1523/jneurosci.22-14-06071.2002

  8. 8.

    Begemann M, Leon M, van der Horn H, van der Naalt J, Sommer I. Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis. Sci Rep. 2020.

    Not in our library10.1038/s41598-020-73227-5

  9. 9.

    Bell M, Kochanek P, Doughty L, Carcillo J, Adelson P, Clark R, Wisniewski S, Whalen M, De Kosky S. Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children. J Neurotrauma. 1997;14:451-457.

    Not in our library10.1089/neu.1997.14.451

  10. 10.

    Bell M, Kochanek P, Carcillo J, Mi Z, Schiding J, Wisniewski S, Clark R, Dixon C, Marion D, Jackson E. Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat. J Neurotrauma. 1998;15:163-170.

    Not in our library10.1089/neu.1998.15.163

  11. 11.

    Block M, Hong J. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77-98.

    Not in our library10.1016/j.pneurobio.2005.06.004

  12. 12.

    Bonneh-Barkay D, Zagadailov P, Zou H, Niyonkuru C, Figley M, Starkey A, Wang G, Bissel S, Wiley C, Wagner A. YKL-40 expression in traumatic brain injury: an initial analysis. J Neurotrauma. 2010;27:1215-1223.

    Not in our library10.1089/neu.2010.1310

  13. 13.

    Breitner JC. Inflammatory processes and antiinflammatory drugs in Alzheimer's disease: a current appraisal. Neurobiol Aging. 1996;17(5):789-94.

    Not in our library10.1016/0197-4580(96)00109-1

  14. 14.

    Cafferty W, Yang S, Duffy P, Li S, Strittmatter S. Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci. 2007;27:2176-2185.

    Not in our library10.1523/jneurosci.5176-06.2007

  15. 15.

    Carbonell W, Mandell J. Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice. J Neurotrauma. 2003;20:327-336.

    Not in our library10.1089/089771503765172282

  16. 16.

    Cernak I, O'Connor C, Vink R. Inhibition of cyclooxygenase 2 by nimesulide improves cognitive outcome more than motor outcome following diffuse traumatic brain injury in rats. Exp Brain Res. 2002;147:193-199.

    Not in our library10.1007/s00221-002-1245-z

  17. 17.

    Chamoun R, Suki D, Gopinath S, Goodman J, Robertson C. Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury. J Neurosurg. 2010;113:564-570.

    Not in our library10.3171/2009.12.jns09689

  18. 18.

    Chi X, Wang S, Huang Y, Stamnes M, Chen J. Roles of rho GTPases in intracellular transport and cellular transformation. Int J Mol Sci. 2013;14:7089-7108.

    Not in our library10.3390/ijms14047089

  19. 19.

    Dash P, Mach S, Moore A. Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury. J Neurotrauma. 2000;17:69-81.

    Not in our library10.1089/neu.2000.17.69

  20. 20.

    Davalos D, Grutzendler J, Yang G, Kim J, Zuo Y, Jung S, Littman D, Dustin M, Gan W. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8:752-758.

    Not in our library10.1038/nn1472

  21. 21.

    Degos V, Chhor V, Gressens P, Mantz J (2022) Neuro-inflammation aiguë et strategies neuroprotectrices. Accessed 18 Apr 2022

    Not in our library

  22. 22.

    Dibble C, Cantley L. Regulation of mTORC1 by PI3K signaling. Trends Cell Biol. 2015;25:545-555.

    Not in our library10.1016/j.tcb.2015.06.002

  23. 23.

    Dietrich W, Bramlett H. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: clinical challenges for successful translation. Brain Res. 2016;1640:94-103.

    Not in our library10.1016/j.brainres.2015.12.034

  24. 24.

    Dubreuil C, Marklund N, Deschamps K, McIntosh T, McKerracher L. Activation of Rho after traumatic brain injury and seizure in rats. Exp Neurol. 2006;198:361-369.

    Not in our library10.1016/j.expneurol.2005.12.002

  25. 25.

    Engel S, Schluesener H, Mittelbronn M, Seid K, Adjodah D, Wehner H, Meyermann R. Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14. Acta Neuropathol. 2000;100:313-322.

    Not in our library10.1007/s004019900172

  26. 26.
    Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A · 2000
    Not checked
  27. 27.

    Gilgun-Sherki Y, Melamed E, Offen D. Anti-inflammatory drugs in the treatment of neurodegenerative diseases: current state. Curr Pharm Des. 2006;12:3509-3519.

    Not in our library10.2174/138161206778343091

  28. 28.

    Gohil K, Patel J, Gajjar A. Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci. 2010;72:546.

    Not in our library10.4103/0250-474x.78519

  29. 29.

    Grilli M, Pizzi M, Memo M, Spano P. Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science. 1996;274(5291):1383-1385.

    Not in our library10.1126/science.274.5291.1383

  30. 30.

    Gugliandolo E, D'Amico R, Cordaro M, Fusco R, Siracusa R, Crupi R, Impellizzeri D, Cuzzocrea S, Di Paola R. Neuroprotective effect of artesunate in experimental model of traumatic brain injury. Front Neurol. 2018.

    Not in our library10.3389/fneur.2018.00590

  31. 31.
    Rapamycin Attenuates the Development of Posttraumatic Epilepsy in a Mouse Model of Traumatic Brain Injury · 2013
    No notice
  32. 32.

    Hakan T, Toklu H, Biber N, Ozevren H, Solakoglu S, Demirturk P, Aker F. Effect of COX-2 inhibitor meloxicam against traumatic brain injury-induced biochemical, histopathological changes and blood–brain barrier permeability. Neurol Res. 2010;32:629-635.

    Not in our library10.1179/016164109x12464612122731

  33. 33.
    The role of the complement system in traumatic brain injury: a review · 2018
    Corrected
  34. 34.

    Harrison J, Rowe R, O’Hara B, Adelson P, Lifshitz J. Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse. Exp Brain Res. 2014;232:2709-2719.

    Not in our library10.1007/s00221-014-3948-3

  35. 35.

    Haynes S, Hollopeter G, Yang G, Kurpius D, Dailey M, Gan W, Julius D. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 2006;9:1512-1519.

    Not in our library10.1038/nn1805

  36. 36.

    He Y, Qu S, Wang J, He X, Lin W, Zhen H, Zhang X. Neuroprotective effects of osthole pretreatment against traumatic brain injury in rats. Brain Res. 2012;1433:127-136.

    Not in our library10.1016/j.brainres.2011.11.027

  37. 37.

    Herrmann J, Imura T, Song B, Qi J, Ao Y, Nguyen T, Korsak R, Takeda K, Akira S, Sofroniew M. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci. 2008;28:7231-7243.

    Not in our library10.1523/jneurosci.1709-08.2008

  38. 38.

    Hovda D, Fu K, Badie H, Samii A, Pinanong P, Becker D (1994) Administration of an omega-conopeptide one hour following traumatic brain injury reduces 45calcium accumulation. Brain Edema IX 521–523

    Not in our library10.1007/978-3-7091-9334-1_143

  39. 39.

    Hu W, Chan G, Lou J, Wu Q, Wang H, Duan R, Cheng M, Dong T, Tsim K. The extract of Polygoni Cuspidati Rhizoma et Radix suppresses the vascular endothelial growth factor-induced angiogenesis. Phytomedicine. 2018;42:135-143.

    Not in our library10.1016/j.phymed.2018.03.029

  40. 40.

    Hutchinson P, O'Connell M, Rothwell N, Hopkins S, Nortje J, Carpenter K, Timofeev I, Al-Rawi P, Menon D, Pickard J. Inflammation in human brain injury: intracerebral concentrations of IL-1α, IL-1β, and their endogenous inhibitor IL-1ra. J Neurotrauma. 2007;24:1545-1557.

    Not in our library10.1089/neu.2007.0295

  41. 41.

    Jassam Y, Izzy S, Whalen M, McGavern D, El Khoury J. Neuroimmunology of traumatic brain injury: time for a paradigm shift. Neuron. 2017;95:1246-1265.

    Not in our library10.1016/j.neuron.2017.07.010

  42. 42.

    Keshavarzi Z, Shakeri F, Barreto G, Bibak B, Sathyapalan T, Sahebkar A. Medicinal plants in traumatic brain injury: Neuroprotective mechanisms revisited. BioFactors. 2019;45:517-535.

    Not in our library10.1002/biof.1516

  43. 43.

    Kong L, Yao Y, Xia Y, Liang X, Ni Y, Yang J. Osthole alleviates inflammation by down-regulating NF-κB signaling pathway in traumatic brain injury. Immunopharmacol Immunotoxicol. 2019;41:349-360.

    Not in our library10.1080/08923973.2019.1608560

  44. 44.

    Kossmann T, Hans V, Imhof H, Trentz O, Morganti-Kossmann M. Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes. Brain Res. 1996;713:143-152.

    Not in our library10.1016/0006-8993(95)01501-9

  45. 45.

    Kossmann T, Stahel P, Morganti-Kossmann M, Jones J, Barnum S. Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury. J Neuroimmunol. 1997;73:63-69.

    Not in our library10.1016/s0165-5728(96)00164-6

  46. 46.

    Kumar V. Regulation of dendritic morphogenesis by ras-PI3K-Akt-mTOR and ras-MAPK signaling pathways. J Neurosci. 2005;25:11288-11299.

    Not in our library10.1523/jneurosci.2284-05.2005

  47. 47.

    Kumar A, Rinwa P, Dhar H. Microglial inhibitory effect of ginseng ameliorates cognitive deficits and neuroinflammation following traumatic head injury in rats. Inflammopharmacology. 2013;22:155-167.

    Not in our library10.1007/s10787-013-0187-3

  48. 48.

    Kunz T, Marklund N, Hillered L, Oliw EH (2022) Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat. In: PubMed. https://www.ncbi.nlm.nih.gov/pubmed/16518028. Accessed 18 Apr 2022

    Not in our library

  49. 49.

    Lagraoui M, Sukumar G, Latoche JR, Maynard SK, Dalgard CL, Schaefer BC. Salsalate treatment following traumatic brain injury reduces inflammation and promotes a neuroprotective and neurogenic transcriptional response with concomitant functional recovery. Brain Behav Immun. 2017;61:96-109.

    Not in our library10.1016/j.bbi.2016.12.005

  50. 50.

    Laird M, Shields J, Sukumari-Ramesh S, Kimbler D, Fessler R, Shakir B, Youssef P, Yanasak N, Vender J, Dhandapani K. High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4. Glia. 2013;62:26-38.

    Not in our library10.1002/glia.22581

  51. 51.

    Lamkanfi M, Walle L, Kanneganti T. Deregulated inflammasome signaling in disease. Immunol Rev. 2011;243:163-173.

    Not in our library10.1111/j.1600-065x.2011.01042.x

  52. 52.

    Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA. Peroxisome proliferatoractivatedreceptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatorydrugs. J Biol Chem. 1997;272(6):3406-3410.

    Not in our library10.1074/jbc.272.6.3406

  53. 53.

    Leveugle B, Fillit H. Proteoglycans and the acutephase response in Alzheimer's disease brain. Mol Neurobiol. 1994;9(1–3):25-32.

    Not in our library10.1007/bf02816102

  54. 54.

    Li D, Liu Z, Wei-Chen M-Y, Li G. Association of glycogen synthase kinase-3β with Parkinson’s disease (Review). Mol Med Rep. 2014;9:2043-2050.

    Not in our library10.3892/mmr.2014.2080

  55. 55.
    Interactions between Sirt1 and MAPKs regulate astrocyte activation induced by brain injury in vitro and in vivo · 2017
    Not checked
  56. 56.
    NF-κB signaling in inflammation · 2017
    No notice
  57. 57.

    Liu X, Zhao Z, Ji R, Zhu J, Sui Q, Knight G, Burnstock G, He C, Yuan H, Xiang Z. Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats. Purinergic Signalling. 2017;13:529-544.

    Not in our library10.1007/s11302-017-9579-y

  58. 58.
    GSK-3β, a pivotal kinase in Alzheimer disease · 2014
    No notice
  59. 59.

    Lozano D, Gonzales-Portillo GS, Acosta S, de la Pena I, Tajiri N, Kaneko Y, Borlongan CV. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatric Dis Treatment. 2015;8;11(11):97-106.

    Not in our library10.2147/ndt.s65815

  60. 60.

    Lucke-Wold B, Seidel K, Udo R, Omalu B, Ornstein M, Nolan R, Rosen C, Ross J. Role of tau acetylation in Alzheimer’s disease and chronic traumatic encephalopathy: the way forward for successful treatment. Journal of Neurology and Neurosurgery. 2017;4(2):140.

    Not in our library

  61. 61.

    Maas A, Roozenbeek B, Manley G. Clinical trials in traumatic brain injury: past experience and current developments. Neurotherapeutics. 2010;7:115-126.

    Not in our library10.1016/j.nurt.2009.10.022

  62. 62.

    Maeda T, Kawane T, Horiuchi N. Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation. Endocrinology. 2003;144:681-692.

    Not in our library10.1210/en.2002-220682

  63. 63.

    Maier B, Schwerdtfeger K, Mautes A, Holanda M, Müller M, Steudel W, Marzi I. Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury. Shock. 2001;15:421-426.

    Not in our library10.1097/00024382-200115060-00002

  64. 64.

    Maier B, Laurer H, Rose S, Buurman W, Marzi I. Physiological levels of pro- and anti-inflammatory mediators in cerebrospinal fluid and plasma: a normative study. J Neurotrauma. 2005;22:822-835.

    Not in our library10.1089/neu.2005.22.822

  65. 65.

    Mattson M, Camandola S. NF-κB in neuronal plasticity and neurodegenerative disorders. J Clin Investig. 2001;107:247-254.

    Not in our library10.1172/jci11916

  66. 66.

    Mbye L, Singh I, Sullivan P, Springer J, Hall E. Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog. Exp Neurol. 2008;209:243-253.

    Not in our library10.1016/j.expneurol.2007.09.025

  67. 67.

    McKeating E, Andrews P. Cytokines and adhesion molecules in acute brain injury. Br J Anaesth. 1998;80:77-84.

    Not in our library10.1093/bja/80.1.77

  68. 68.

    Menet V, Prieto M, Privat A, Ribotta M. Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci. 2003;100:8999-9004.

    Not in our library10.1073/pnas.1533187100

  69. 69.

    Meng X, Li N, Zhang Y, Fan D, Yang C, Li H, Guo D, Pan S. Beneficial effect of β-elemene alone and in combination with hyperbaric oxygen in traumatic brain injury by inflammatory pathway. Transl Neurosci. 2018;9:33-37.

    Not in our library10.1515/tnsci-2018-0007

  70. 70.

    Momtazi A, Shahabipour F, Khatibi S, Johnston T, Pirro M, Sahebkar A (2016) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 1–38

    Not in our library10.1007/112_2016_3

  71. 71.

    Morganti-Kossman M, Lenzlinger P, Hans V, Stahel P, Csuka E, Ammann E, Stocker R, Trentz O, Kossmann T. Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Mol Psychiatry. 1997;2:133-136.

    Not in our library10.1038/sj.mp.4000227

  72. 72.

    Morganti-Kossmann M, Hans V, Lenzlinger P, Dubs R, Ludwig E, Trentz O, Kossmann T. TGF-β is elevated in the CSF of patients with severe traumatic brain injuries and parallels blood-brain barrier function. J Neurotrauma. 1999;16:617-628.

    Not in our library10.1089/neu.1999.16.617

  73. 73.

    Morganti-Kossmann M, Satgunaseelan L, Bye N, Kossmann T. Modulation of immune response by head injury. Injury. 2007;38:1392-1400.

    Not in our library10.1016/j.injury.2007.10.005

  74. 74.
    RhoA-ROCK Signaling as a Therapeutic Target in Traumatic Brain Injury · 2020
    No notice
  75. 75.

    Müller N. COX-2 inhibitors, aspirin, and other potential anti-inflammatory treatments for psychiatric disorders. Front Psych. 2019.

    Not in our library10.3389/fpsyt.2019.00375

  76. 76.

    Niswender C, Conn P. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol. 2010;50:295-322.

    Not in our library10.1146/annurev.pharmtox.011008.145533

  77. 77.

    Oliva A, Kang Y, Sanchez-Molano J, Furones C, Atkins C. STAT3 signaling after traumatic brain injury. J Neurochem. 2012;120:710-720.

    Not in our library10.1111/j.1471-4159.2011.07610.x

  78. 78.

    Otani N, Nawashiro H, Fukui S, Nomura N, Yano A, Miyazawa T, Shima K. Differential activation of mitogen-activated protein kinase pathways after traumatic brain injury in the rat hippocampus. J Cereb Blood Flow Metab. 2002;22:327-334.

    Not in our library10.1097/00004647-200203000-00010

  79. 79.

    Pinteaux E, Parker L, Rothwell N, Luheshi G. Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells. J Neurochem. 2002;83:754-763.

    Not in our library10.1046/j.1471-4159.2002.01184.x

  80. 80.

    PMC E (2022) Europe PMC. In: Europepmc.org. https://europepmc.org/article/MED/21038663. Accessed 18 Apr 2022

    Not in our library

  81. 81.

    Qin H, Qin J, Hu J, Huang H, Ma L. Malva sylvestris attenuates cognitive deficits in a repetitive mild traumatic brain injury rat model by reducing neuronal degeneration and astrocytosis in the hippocampus. Med Sci Monit. 2017;23:6099-6106.

    Not in our library10.12659/msm.905429

  82. 82.

    Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998;391(6662):79-82.

    Not in our library10.1038/34178

  83. 83.

    Rothwell N. Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain Behav Immun. 2003;17:152-157.

    Not in our library10.1016/s0889-1591(02)00098-3

  84. 84.

    Samini F, Samarghandian S, Borji A, Mohammadi G, Bakaian M. Curcumin pretreatment attenuates brain lesion size and improves neurological function following traumatic brain injury in the rat. Pharmacol Biochem Behav. 2013;110:238-244.

    Not in our library10.1016/j.pbb.2013.07.019

  85. 85.
    Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury · 2014
    No notice
  86. 86.

    Schousboe A, Waagepetersen H. Role of astrocytes in glutamate homeostasis: Implications for excitotoxicity. Neurotox Res. 2005;8:221-225.

    Not in our library10.1007/bf03033975

  87. 87.

    Schouten J. Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature. Curr Opin Crit Care. 2007;13:134-142.

    Not in our library10.1097/mcc.0b013e3280895d5c

  88. 88.

    Semple B, Bye N, Rancan M, Ziebell J, Morganti-Kossmann M. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2−/− mice. J Cereb Blood Flow Metab. 2009;30:769-782.

    Not in our library10.1038/jcbfm.2009.262

  89. 89.

    Singh S, Singh T. Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: an mechanistic approach. Curr Neuropharmacol. 2020;18:918-935.

    Not in our library10.2174/1570159x18666200207120949

  90. 90.

    Singh I, Sullivan P, Deng Y, Mbye L, Hall E. Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J Cereb Blood Flow Metab. 2006;26:1407-1418.

    Not in our library10.1038/sj.jcbfm.9600297

  91. 91.

    Singh P, Singh S, Kapoor I, Singh G, Isidorov V, Szczepaniak L. Chemical composition and antioxidant activities of essential oil and oleoresins from Curcuma zedoaria rhizomes, part-74. Food Biosci. 2013;3:42-48.

    Not in our library10.1016/j.fbio.2013.06.002

  92. 92.

    Siopi E, Llufriu-Dabén G, Cho A, Vidal-Lletjós S, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Etazolate, an α-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice. Neuropharmacology. 2013;67:183-192.

    Not in our library10.1016/j.neuropharm.2012.11.009

  93. 93.

    Stirling D. Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci. 2004;24:2182-2190.

    Not in our library10.1523/jneurosci.5275-03.2004

  94. 94.

    Stover J, Schöning B, Beyer T, Woiciechowsky C, Unterberg A. Temporal profile of cerebrospinal fluid glutamate, interleukin-6, and tumor necrosis factor-α in relation to brain edema and contusion following controlled cortical impact injury in rats. Neurosci Lett. 2000;288:25-28.

    Not in our library10.1016/s0304-3940(00)01187-3

  95. 95.

    Suzuki T, Yamamoto M. Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress. J Biol Chem. 2017;292:16817-16824.

    Not in our library10.1074/jbc.r117.800169

  96. 96.

    Swartz K, Liu F, Sewell D, Schochet T, Campbell I, Sandor M, Fabry Z. Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res. 2001;896:86-95.

    Not in our library10.1016/s0006-8993(01)02013-3

  97. 97.

    Taylor R, Chang C, Goods B, et al. TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J Clin Investig. 2016;127:280-292.

    Not in our library10.1172/jci88647

  98. 98.

    Tehranian R, Andell-Jonsson S, Beni S, Yatsiv I, Shohami E, Bartfai T, Lundkvist J, Iverfeldt K. Improved recovery and delayed cytokine induction after closed head injury in mice with central overexpression of the secreted isoform of the interleukin-1 receptor antagonist. J Neurotrauma. 2002;19:939-951.

    Not in our library10.1089/089771502320317096

  99. 99.

    Thau-Zuchman O, Shohami E, Alexandrovich A, Trembovler V, Leker R. The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury. J Neurotrauma. 2012;29:375-384.

    Not in our library10.1089/neu.2010.1673

  100. 100.

    Tuttolomondo A, Pecoraro R, Pinto A (2014) Studies of selective TNF inhibitors in the treatment of brain injury from stroke and trauma: a review of the evidence to date. Drug Design Dev Therapy 2221

    Not in our library10.2147/dddt.s67655

  101. 101.

    Vosough-Ghanbari S, Rahimi R, Kharabaf S, et al. Effects of Satureja khuzestanica on serum glucose, lipids and markers of oxidative stress in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial. Evid-Based Complement Altern Med. 2010;7:465-470.

    Not in our library10.1093/ecam/nen018

  102. 102.

    Wang K, Zhang L, Rao W, Su N, Hui H, Wang L, Peng C, Tu Y, Zhang S, Fei Z. Neuroprotective effects of crocin against traumatic brain injury in mice: Involvement of notch signaling pathway. Neurosci Lett. 2015;591:53-58.

    Not in our library10.1016/j.neulet.2015.02.016

  103. 103.

    Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99:4-9.

    Not in our library10.1093/bja/aem131

  104. 104.

    Whalen M, Carlos T, Kochanek P, Wisniewski S, Bell M, Clark R, DeKosky S, Marion D, Adelson D. Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med. 2000;28:929-934.

    Not in our library10.1097/00003246-200004000-00003

  105. 105.

    Wilhelmsson U. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004;24:5016-5021.

    Not in our library10.1523/jneurosci.0820-04.2004

  106. 106.

    Winter C. Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury. Brain. 2004;127:315-320.

    Not in our library10.1093/brain/awh039

  107. 107.

    Winter C, Iannotti F, Pringle A, Trikkas C, Clough G, Church M. A microdialysis method for the recovery of IL-1β, IL-6 and nerve growth factor from human brain in vivo. J Neurosci Methods. 2002;119:45-50.

    Not in our library10.1016/s0165-0270(02)00153-x

  108. 108.

    Xiong Y, Gu Q, Peterson P, Muizelaar J, Lee C. Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J Neurotrauma. 1997;14:23-34.

    Not in our library10.1089/neu.1997.14.23

  109. 109.

    Xu X, Wu X. RhoA/Rho kinase in spinal cord injury. Neural Regen Res. 2016;11:23.

    Not in our library10.4103/1673-5374.169601

  110. 110.

    Xu L, Fagan S, Waller J, Edwards D, Borlongan C, Zheng J, Hill W, Feuerstein G, Hess D. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004.

    Not in our library10.1186/1471-2377-4-7

  111. 111.

    Yang K, Mu X, Hayes R. Increased cortical nuclear factor-κB (NF-κB) DNA binding activity after traumatic brain injury in rats. Neurosci Lett. 1995;197:101-104.

    Not in our library10.1016/0304-3940(95)11919-n

  112. 112.

    Yulug B, Kilic E, Altunay S, Ersavas C, Orhan C, Dalay A, Tuzcu M, Sahin N, Juturu V, Sahin K. Cinnamon polyphenol extract exerts neuroprotective activity in traumatic brain injury in male mice. CNS Neurol Disord Drug Targets. 2018;17:439-447.

    Not in our library10.2174/1871527317666180501110918

  113. 113.

    Zhang Z, Zhang Z, Artelt M, Burnet M, Schluesener H. Dexamethasone attenuates early expression of three molecules associated with microglia/macrophages activation following rat traumatic brain injury. Acta Neuropathol. 2007;113:675-682.

    Not in our library10.1007/s00401-007-0195-8

  114. 114.

    Zhao Z, Alam S, Oppenheim R, Prevette D, Evenson A, Parsadanian A. Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy. Exp Neurol. 2004;190:356-372.

    Not in our library10.1016/j.expneurol.2004.06.015

  115. 115.

    Zhao J, Li G, Zhang Y, Su X, Hang C. The potential role of JAK2/STAT3 pathway on the anti-apoptotic effect of recombinant human erythropoietin (rhEPO) after experimental traumatic brain injury of rats. Cytokine. 2011;56:343-350.

    Not in our library10.1016/j.cyto.2011.07.018

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