Erythropoietin As A Protective Cytokine In Experimental Subarachnoid Hemorrhage

Background and objectiveThe patho-physiological mechanism after subarachnoid hemorrhage (SAH) is complex. Toxic effection of blood cells and it's decomposed products in subarachnoid cavity, oxyradical, inflammatory reaction, nitric oxide path, apoptosis in the endothelium and other mechanisms may take part in the onset and development of cerebral vasospasm(CVS). Simultaneously, most of these etiological factors may also cause brain injury. Clinically, drug treatment mainly focus on two aspects: preventing and reducing cerebrovascular vasospasm and neuroprotection. In recent years, as a protective agent, erythropoietin (EPO) has been studied widely. In various animal experiment models (ischemia model, press and contend model, kainic acid evoked epilepsia model, disseminated sclerosis model, and hyperglycaemia model), it was confirmed that EPO has neuroprotective effect either in vivo or in vitro. Several mechanisims have been launched to explain neuroprotective effect of EPO, including inhibiting production of aminoglutaminic acid, stimulating regeneration of vascellum, adjusting transport of synapse, inhibiting apoptosis, suppressing inflammatory reaction, neurotrophy, and so on. Recent research also demonstrated that EPO could reduce the CVS after SAH. At present, the studies on reducing CVS or neuroprotective effect of EPO in SAH still remain on animal experiment stage, moreover, the mechanism of EPO's effect of reducing CVS is not clear. The relevant reports about EPO's effect in SAH are scarce, and no report is published in domestic. The following study is going to confirm EPO's effect of neuroprotection and reducing CVS in SAH, furthermore, by detecting the apoptosis of blood vessel endothelium, we try to deduce whether protecting vessel endothelium is one of the mechanisms of EPO's effect of reducing CVS.Methodsthirty male rabbits, weight 2.8-3.3 kg,were equally randomized to five groups: non-treatment, control, SAH, SAH plus placebo, and SAH plus recombinant human erythropoietin(rHuEPO). The rabbit SAH model was constructed by autologous blood(non-anticoagulated arterial blood 2ml) injection into the cisterna magna. 48 hours after the blood-injection, the content of S-100B protein in cerebrospinal fluid was determined by enzyme-linked immunoassay and perfusion-fixation was performed in vivo. The cross-sectional area of each basilar arterial lumen was measured to evaluate the degree of cerebral vasospasm. TUNEL was used to observe the apoptosis of endothelial cells in the basilar artery and temporal lobar cortex.ResultsThe average cross-sectional area of basilar arteries was no significant difference between non-treatment group and control group or between SAH group and SAH plus placebo group. The cross-sectional areas of basilar arteries in SAH plus rHuEPO group were larger than those of SAH group or SAH plus placebo group(P<0.01), but smaller than non-treatment group or control group(P<0.01). TUNEL revealed that apoptosis level of endothelial cells in SAH plus rHuEPO group was lower than in SAH group or SAH plus placebo group(P<0.05), and apoptosis level of temporal lobar cortex in SAH plus rHuEPO group was lower than in SAH group or SAH plus placebo group(P<0.05).ConclusionEarly systemic administration of rHuEPO shows obvious protective effect in rabbit SAH model, including decreasing the apoptosis level of temporal lobar cortex, reducing the concentration of S-100B protein in cerebrospinal fluid and partially attenuating CVS, and protecting vessel endothelium may be one of the mechanisms of EPO's effect of reducing CVS.