Neuroprotective effect of recombinant human erythropoietin in experimental subarachnoid hemorrhage.
BACKGROUND
Acute cerebral vasoconstriction and subsequent brain ischemia, often occurring in the early phase of subarachnoid hemorrhage (SAH), are critical problems in the management of patients affected by ruptured intracranial aneurysms. It is known that nitric oxide (NO) decreases during SAH with impairment of cerebrovascular relaxation, and glutamate is mainly involved in the consequent brain ischemic damage. Recently, erythropoietin (EPO) has shown to exert a neuroprotective effect during cerebral ischemia by enhancing the NO system activity. In the present study the effect of systemic administration of recombinant human erythropoietin (rHuEPO) has been investigated in a rabbit model of SAH.


METHODS
Thirty-two rabbits were assigned to four groups: 1) Control; 2) SAH; 3) SAH plus placebo; 4) SAH plus rHuEPO. Experimental SAH was induced by injecting autologous blood into the cisterna magna. rHuEPO, at a dose of 1000 IU/kg, and placebo were given 5 minutes after SAH. Administration was repeated three times during 24 hours. The animals were killed 24 hours after SAH by a perfusion-fixation method. Luminal cross-sections of the basilar artery were measured by computer-assisted morphometric analysis. Ischemic injury was histologically evaluated by analysis of the frequency of ischemia-induced damaged cortical neurons.


RESULTS
Administration of rHuEPO significantly reversed the vasoconstriction of the basilar artery in Group 4 compared with the other groups (p<0.05). Histological examination showed a significant reduction in total damaged neurons count in Group 4 compared with the other groups (p<0.01).


CONCLUSIONS
These results suggest that rHuEPO is effective in attenuating acute cerebral vasoconstriction and ischemic brain injury following experimental SAH.
Grasso
G
G
Department of Neurosurgery, University of Messina, Messina, Italy. giovanni.grasso@unime.it
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide; D018698:Glutamic Acid