Neuroinflammation in Cerebral Ischemia and Ischemia/Reperfusion Injuries: From Pathophysiology to Therapeutic Strategies

Abstract

Its increasing incidence has led stroke to be the second leading cause of death worldwide. Despite significant advances in recanalization strategies, patients are still at risk for ischemia/reperfusion injuries in this pathophysiology, in which neuroinflammation is significantly involved. Research has shown that in the acute phase, neuroinflammatory cascades lead to apoptosis, disruption of the blood–brain barrier, cerebral edema, and hemorrhagic transformation, while in later stages, these pathways support tissue repair and functional recovery. The present review discusses the various cell types and the mechanisms through which neuroinflammation contributes to parenchymal injury and tissue repair, as well as therapeutic attempts made in vitro, in animal experiments, and in clinical trials which target neuroinflammation, highlighting future therapeutic perspectives.

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury

“…In lesions caused by I/R, inflammation is initiated by stagnant blood flow (vessel occlusion) and is then maintained by leukocytes activation and release of proinflammatory cytokines. Reducing or stopping the blood flow causes changes in the coagulation cascade, activates NF-kB and increases the expression of adhesion molecules on endothelial cells (Jurcau and Simion, 2021). Decreasing the amount of oxygen in the tissue causes varying degrees of damage.…”

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

“…In addition, miR-98-5p inhibited apoptosis by increasing Bcl-2 levels and by reducing Bax and cleaved caspase-3 levels [206]. Other microRNAs, such as miR133b [207] or miR-124-3p [208], can modulate brain plasticity and neuroinflammation following ischemic stroke [209], contributing to angiogenesis, neurogenesis, oligodendrogenesis, and astrogenesis, and improve functional recovery if administered in a prolonged time window after the ischemic insult (days to months after stroke) [210]. Technical issues relating to the appropriate timing of mesenchymal stem cell transfer, the route of administration, and the characterization of the stem cells need to be solved [211], but clinical trials have already been carried out on a small scale and show the therapy to be safe and to lead to significant functional improvement [212].…”

Neuroinflammation in Vascular Cognitive Impairment and Dementia: Current Evidence, Advances, and Prospects

“…In cerebral ischemic diseases, blood flow stagnation will lead to inflammatory reactions. When inflammation is activated, glial cells, neutrophils, monocytes and lymphocytes are activated, as are pro-inflammatory cytokines and inflammatory-related metabolites, promoting the continuous occurrence of inflammation, ultimately causing persistent tissue damage [ 60 , 61 , 62 ]. This inflammatory response can be divided into four periods [ 63 , 64 , 65 , 66 ]: (1) During the acute phase, microglia or macrophages remove necrotic and fragmented cells; (2) During the subacute stage, oxidative stress occurs, which promotes the generation of inflammatory mediators such as cytokines and adhesion molecules, and continuously induces inflammatory response; (3) During the chronic phase, inflammatory mediators and reactive oxygen species lead to mitochondrial and DNA damage, triggering cell necrosis and apoptosis for several days; (4) During the recovery period, with the decrease in inflammatory response level, various nutritional factors will be released to supplement cell damage caused by apoptosis.…”