Beneficial effects of systemic administration of recombinant human erythropoietin in rabbits subjected to subarachnoid hemorrhage.
Cerebral vasospasm and ischemic damage are important causes of mortality and morbidity in patients affected by aneurysmal subarachnoid hemorrhage (SAH). Recently, i.p. administration of recombinant human erythropoietin (r-Hu-EPO) has been shown to exert a neuroprotective effect during experimental SAH. The present study was conducted to evaluate further the effect of r-Hu-EPO administration after SAH in rabbits on neurological outcome, degree of basilar artery spasm, and magnitude of neuronal ischemic damage. Experimental animals were divided into six groups: group 1 (n = 8), control; group 2 (n = 8), control plus placebo; group 3 (n = 8), control plus r-Hu-EPO; group 4 (n = 8), SAH; group 5 (n = 8), SAH plus placebo; group 6 (n = 8), SAH plus r-Hu-EPO. r-Hu-EPO, at a dose of 1,000 units/kg, and placebo were injected i.p. starting 5 min after inducing SAH and followed by clinical and pathological assessment 72 h later. Systemic administration of r-Hu-EPO produced significant increases in cerebrospinal fluid EPO concentrations (P < 0.001), and reduced vasoconstriction of the basilar artery (P < 0.05), ischemic neuronal damage (P < 0.001), and subsequent neurological deterioration (P < 0.05). These observations suggest that r-Hu-EPO may provide an effective treatment to reduce the post-SAH morbidity.
Grasso
Giovanni
G
Department of Neurosurgery, University of Messina, 98122 Messina, Italy. giovanni.grasso@unime.it
Buemi
Michele
M
Alafaci
Concetta
C
Sfacteria
Alessandra
A
Passalacqua
Marcello
M
Sturiale
Alessio
A
Calapai
Gioacchino
G
De Vico
Gionata
G
Piedimonte
Giuseppe
G
Salpietro
Francesco M
FM
Tomasello
Francesco
F
D000818:Animals; D004921:Erythropoietin / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009474:Neurons / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin