Understanding brain dysfunction in sepsis

Abstract

Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood-brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke's encephalopathy. Modulation of microglial activation, prevention of blood-brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.

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Cited by papers we hold 14

• Astrocytes in human central nervous system diseases: a frontier for new therapies · 2023
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• Risk of Dementia or Cognitive Impairment in Sepsis Survivals: A Systematic Review and Meta-Analysis · 2022
  Not checked
• Sepsis‐Induced Brain Dysfunction: Pathogenesis, Diagnosis, and Treatment · 2022
  No notice
• Early postoperative seizures in liver and kidney recipients · 2021
  Not checked
• The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020) · 2021
  No notice
• Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy · 2021
  No notice
• Exosomes in Sepsis · 2020
  Not checked
• The Pathogenesis of Sepsis and Potential Therapeutic Targets · 2019
  No notice
• Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms · 2019
  No notice
• Platelets in Sepsis: An Update on Experimental Models and Clinical Data · 2019
  No notice
• NADPH oxidases as potential pharmacological targets against increased seizure susceptibility after systemic inflammation · 2018
  Not checked
• Antibiotics Induced Seizures and Encephalopathy · 2018
  Not checked
• Systemic Inflammation and the Brain: Novel Roles of Genetic, Molecular, and Environmental Cues as Drivers of Neurodegeneration · 2015
  No notice
• Sepsis Associated Encephalopathy · 2014
  No notice

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