Brain Ischemic Injury in Rodents: The Protective Effect of EPO

Abstract

Animal models constitute an indispensable tool to investigate human pathology. Here we describe the procedure to induce permanent and transient cerebral ischemia in the mouse and the rat. The model of transient occlusion of the middle cerebral artery (MCA) is performed by the insertion of an occlusive filament until the origin of the MCA while the permanent occlusion described in the mice is performed by a distal electrocoagulation of the MCA. Those models allow evaluating the efficiency of therapeutic strategy of ischemia from tissular aspect to behavioral and cognitive impairment assessment. They were widely used in the literature to evaluate the efficiency of different drugs including the cytokines and especially erythropoietin (EPO) or its derivatives.

Influence of Electric Acupuncture on Bcl-xl and Caspase-3 Expression After Cerebral Ischemia of Rats

“…The research indicates that after focal cerebral ischemia, EPO starts phosphorylation of downstream factor STAT5 through mediating EPOR-JAK2-STAT5 signal transduction approach. The activated STAT5 can effectively up-regulate expression of Bcl-2, Bcl-xl and other inhibitors of apoptosis protein, benignly down-regulate expression of Bax, Caspase-3 and other pro-apoptotic protein, and effectively prevent cytochrome C from releasing from mitochondria so as to give play to the anti-apoptosis effect after cerebral ischemia [6][7][8] . The research result prompts that Acupuncturing Baihui point and Dazhui can effectively regulate expression of key target spots after cerebral ischemia and suppress neuronal apoptosis.…”

Decrease in Oxidative Stress Parameters after Post‐Ischaemic Recombinant Human Erythropoietin Administration in the Hippocampus of Rats Exposed to Focal Cerebral Ischaemia

“…Recombinant human erythropoietin (rhEpo) is a clinically approved drug whose indications are currently restricted to the treatment of anaemia in renal failure and cancer . Several hypotheses of potential neuroprotective effect of rhEpo were based either on direct cytoprotective mechanisms activated by increase in anti‐apoptotic proteins and Bcl‐X L /Bax ratio or reduction in pro‐apoptotic factors like active caspases, suppression of matrix metalloproteinases, inhibition of glutamate excitotoxicity, modulation of nitric oxide synthase and enhancement of the brain's antioxidant defences or on indirect activation via its angiogenic potential and improvement of cerebral blood flow in the ischaemic tissue . The capability of rhEpo to cross the blood–brain barrier after systemic administration, its acceptable therapeutic window and good clinical tolerability are additional advantages for its potential application in human stroke therapy .…”