Does administration of recombinant human erythropoietin attenuate the increase of S-100 protein observed in cerebrospinal fluid after experimental subarachnoid hemorrhage?
OBJECTIVE
Results of recent studies indicate that erythropoietin (EPO) produces a neuroprotective effect on experimental subarachnoid hemorrhage (SAH). It has been reported that S-100 protein levels increase in cerebrospinal fluid (CSF) after SAH, providing a highly prognostic indication of unfavorable outcome. This study was conducted to validate further the findings of S-100 protein as an index of brain damage and to assess whether treatment with recombinant human EPO (rhEPO) would limit the increase of S-100 protein level in CSF following experimental SAH.


METHODS
Thirty-two rabbits were each assigned to one of four groups: Group 1, control; Group 2, SAH; Group 3, SAH plus placebo; and Group 4, SAH plus rhEPO (each group consisted of eight rabbits). The rhEPO and placebo were administered to the rabbits after SAH had been induced, and S-100 protein levels in the CSF of these animals were measured at 24, 48, and 72 hours after the experimental procedure. In each group of animals levels of S-100 protein were compared with the mortality rate, neurological outcome, and neuronal ischemic damage. High S-100 protein levels were found in rabbits in Groups 2 and 3, which exhibited poor neurological status and harbored a high number of damaged cortical neurons. Favorable neurological outcome and significant reductions in total numbers of damaged neurons were observed in animals in Group 4 in which there were significantly lower S-100 protein concentrations compared with animals in Groups 2 and 3 (p < 0.001).


CONCLUSIONS
The results of this study support the concept that determination of the S-100 protein level in CSF has prognostic value after SAH. The findings also confirm that rhEPO acts as a neuroprotective agent during experimental SAH.
Grasso
Giovanni
G
Department of Neurosurgery, University of Messina, Policlinico Universitario, Italy. Giovanni.Grasso@unime.it
Passalacqua
Marcello
M
Sfacteria
Alessandra
A
Conti
Alfredo
A
Morabito
Antonio
A
Mazzullo
Giuseppe
G
De
Vico Gionata
VG
Buemi
Michele
M
Macrì
Battesimo
B
Tomasello
Francesco
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001925:Brain Damage, Chronic / Q000134:cerebrospinal fluid / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009460:Neurologic Examination / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins; D009418:S100 Proteins / Q000134:cerebrospinal fluid*; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000473:pathology
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D009418:S100 Proteins; D004921:Erythropoietin