Neuroinflammation in Post-Ischemic Brain

Abstract

Acute neuroinflammation occurring immediately after cerebral ischemia lasts for a few days.Cytokines and chemokines promote the migration of neutrophils and macrophages to the site of inflammation in the brain. Neuroinflammation lasting 2-6 weeks is known as subacute neuroinflammation, while chronic post-ischemic inflammation lasts for months or years.Macrophages, lymphocytes, and plasma cells predominate in chronic neuroinflammation, in contrast to neutrophils that predominate in acute neuroinflammation. In addition to their harmful impact on the ischemic brain, inflammatory mediators may also exert beneficial effects in stroke recovery. The role of secondary inflammatory cells in the pathophysiology of brain ischemia are still less understood. Late post-ischemic neuroinflammation leads to secondary damage of neuronal cells. In this chapter, the role of leukocytes, T cells, T regs, B cells, neutrophils, macrophages, microglia, astrocytes, cytokines, and transcription factors in the post-ischemic brain are discussed. Post-ischemic thrombo-inflammation and the role of platelets, recently considered as a part of the innate immune system, are also addressed. The current pharmacotherapy and future strategies for the treatment of neuroinflammation in post-ischemic brain as well as the limitations of translation between preclinical and clinical studies are presented.

3,6′- and 1,6′-Dithiopomalidomide Mitigate Ischemic Stroke in Rats and Blunt Inflammation

“…Ischemic stroke triggers a vigorous inflammatory response initiated within minutes and persisting for days [ 45 , 46 ]. After ischemic stroke, a secondary immune response occurs that includes glial activation and release of cytokines and chemokines.…”

“…Minutes to hours after stroke, the acute phase of stroke leads to production of pro-inflammatory cytokines, particularly IL-1β and TNF-α, which propagate the neuroinflammatory response through activation of danger signals [ 7 , 45 ]. To investigate the regulation of pomalidomide and analogs on global inflammatory responses after ischemic stroke, we quantified pro- and anti-inflammatory cytokine levels.…”

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

“…Possible causative mechanisms of CNS inflammation and neuroglial reactivity include direct effects through injury or infection of the brain, reactivation of endogenous microbial reservoirs in CNS cells, autoimmune reactivity with specific neural, glial, or immune system targets, repetitive mechanical strain, cerebrovascular hypertension, cerebral hypoperfusion and/or ischemia, recognition of danger-associated molecular patterns (DAMP), vagal dysfunction, norepinephrine or angiotensin II overload, or, generally, exposure to chronic stress ( VanElzakker, 2013 ; Verkhratsky and Parpura, 2014 ; Calcia et al, 2016 ; Yang and Zhou, 2019 ; Živančević et al, 2021 ). Also, CNS inflammation can be initiated by any disruption of the BBB – caused, for instance by peripheral microvascular dysfunction (e.g., from endothelial inflammation or abnormal coagulation) or by peripheral – acute or chronic –inflammation.…”

In vivo protective effects of 6‑gingerol in cerebral ischemia involve preservation of antioxidant defenses and activation of anti‑apoptotic pathways

“…Excessive production of reactive oxygen species (ROS) such as superoxide anions, hydroxyl radicals and hydrogen peroxide may cause oxidative stress-induced cell injury ( 4 ). Cerebral ischemia also initiates an inflammatory response in the brain, involving the activation of immune cells such as microglia and astrocytes, as well as the release of inflammatory mediators including cytokines, chemokines and adhesion molecules ( 5 ). This inflammatory response can exacerbate neuronal damage by promoting additional ROS production and causing the breakdown of the blood-brain barrier, enabling immune cells and harmful substances to enter the brain ( 6 , 7 ).…”