How Long Are Reperfusion Therapies Beneficial for Patients after Stroke Onset? Lessons from Lethal Ischemia Following Early Reperfusion in a Mouse Model of Stroke

Abstract

Ischemic stroke caused by cerebral artery occlusion induces neurological deficits because of cell damage or death in the central nervous system. Given the recent therapeutic advances in reperfusion therapies, some patients can now recover from an ischemic stroke with no sequelae. Currently, reperfusion therapies focus on rescuing neural lineage cells that survive in spite of decreases in cerebral blood flow. However, vascular lineage cells are known to be more resistant to ischemia/hypoxia than neural lineage cells. This indicates that ischemic areas of the brain experience neural cell death but without vascular cell death. Emerging evidence suggests that if a vascular cell-mediated healing system is present within ischemic areas following reperfusion, the therapeutic time window can be extended for patients with stroke. In this review, we present our comments on this subject based upon recent findings from lethal ischemia following reperfusion in a mouse model of stroke.

Different Contacted Cell Types Contribute to Acquiring Different Properties in Brain Microglial Cells upon Intercellular Interaction

“…Therefore, under physiological conditions, ECs might negatively regulate MG numbers. Like PCs, ECs are resistant to hypoxia and could survive even after an ischemic stroke [ 17 , 20 , 21 , 22 , 23 ]; this was supported by this study because certain CD31 + ECs were present in ischemic areas. However, under pathological conditions, endothelial intercellular junctions are loosened, and injured ECs cause BBB dysfunction [ 49 , 50 ].…”

“…Therefore, MGs and ACs could establish again direct cell–cell contacts around the ischemic areas. Unlike ACs, PCs and ECs are resistant to hypoxia and could survive within the ischemic areas for several days even after a permanent ischemia [ 17 , 20 , 21 , 22 , 23 ]. Furthermore, the number of PDGFRβ + PCs reportedly increases within the ischemic areas after an ischemic stroke [ 17 , 19 ].…”

Influence of Melatonin on Behavioral and Neurological Function of Rats with Focal Cerebral Ischemia-Reperfusion Injury via the JNK/FoxO3a/Bim Pathway

“…However, in the reperfusion process of recovering blood flow after cerebral ischemia, it will cause more serious damage to brain tissue, namely ischemia-reperfusion injury (IRI) [ 6 ]. Because of the long-term ischemia of brain tissue, local inflammation and reactive oxygen species accelerate to produce when the blood supply returns to normal, which, instead of promoting the recovery of brain function, will aggravate brain injury and capillary dysfunction and lead to secondary brain injury, brain edema, hemorrhagic transformation, necrosis, and free radical injury with infarction growth, resulting in strong neuroinflammatory reaction and even death in severe cases [ 7 , 8 ]. The formation of focal cerebral ischemia injury is closely associated with neuronal apoptosis [ 9 ].…”

The Influence of Mitochondrial-DNA-Driven Inflammation Pathways on Macrophage Polarization: A New Perspective for Targeted Immunometabolic Therapy in Cerebral Ischemia-Reperfusion Injury

“…As such, it plays an important role in severe trauma, non-hemolytic transfusion reactions, and ischemia-reperfusion injury discussed in this article [ 169 ]. However, some problems still exist, such as the heterogeneity of the polarization level of macrophages in the injured area and the difficulty of defining the administration time in the acute and subacute phases in the experiment [ 170 ]. However, the polarization state of macrophages/microglia in the immune microenvironment of the brain does affect the prognostic effect after reperfusion.…”