Depletion of microglia exacerbates postischemic inflammation and brain injury

Abstract

Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of microglia has been linked to worse stroke outcomes, it remains unclear to what extent and by what mechanisms activated microglia influence ischemia-induced inflammation and injury in the brain. Using a mouse model of transient focal cerebral ischemia and reperfusion, we demonstrated that depletion of microglia via administration of the dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits and brain infarction. Depletion of microglia augmented the production of inflammatory mediators, leukocyte infiltration, and cell death during brain ischemia. Of note, microglial depletion-induced exacerbation of stroke severity did not solely depend on lymphocytes and monocytes. Importantly, depletion of microglia dramatically augmented the production of inflammatory mediators by astrocytes after brain ischemia . In vitro studies reveal that microglia restricted ischemia-induced astrocyte response and provided neuroprotective effects. Our findings suggest that neuroprotective effects of microglia may result, in part, from its inhibitory action on astrocyte response after ischemia.

Cited by papers we hold 20

• Prolonged anesthesia induces neuroinflammation and complement-mediated microglial synaptic elimination involved in neurocognitive dysfunction and anxiety-like behaviors · 2023
  No notice
• Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination · 2022
  No notice
• Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention · 2022
  Not checked
• Neuroinflammation, Microglia and Implications for Retinal Ganglion Cell Survival and Axon Regeneration in Traumatic Optic Neuropathy · 2022
  No notice
• Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice · 2022
  No notice
• Microglia-mediated neuroinflammation and neuroplasticity after stroke · 2022
  No notice
• Understanding Acquired Brain Injury: A Review · 2022
  No notice
• Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function · 2021
  No notice
• Microglial/Macrophage polarization and function in brain injury and repair after stroke · 2021
  No notice
• Depletion of microglia exacerbates injury and impairs function recovery after spinal cord injury in mice · 2020
  No notice
• FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages · 2020
  No notice
• Neuroinflammation: friend and foe for ischemic stroke · 2019
  No notice
• Effect of Inflammation on the Process of Stroke Rehabilitation and Poststroke Depression · 2019
  Not checked
• Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti‐inflammatory phenotype through STAT3 pathway · 2019
  No notice
• Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain · 2019
  No notice
• Pterostilbene Attenuates Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation · 2019
  No notice
• Microglia and CNS Interleukin-1: Beyond Immunological Concepts · 2018
  No notice
• An updated assessment of microglia depletion: current concepts and future directions · 2017
  No notice
• Microglial Activation in Traumatic Brain Injury · 2017
  No notice
• Pertussis toxin–induced inflammatory response exacerbates intracerebral haemorrhage and ischaemic stroke in mice
  Not checked

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.