Dose-dependent ultrastructural and morphometric alterations after erythropoietin treatment in rat femoral artery vasospasm model.
OBJECTIVE
Cerebral vasospasm is the common cause of poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). Although many agents are experimentally and clinicaly used to protect or recover from vasospasm, an effective neurotherapeutic drug is still missing. Erythropoietin (EPO) is recently a promising candidate. The aim of this study is to investigate the dose-dependent effects of recombinant human EPO (rhEPO) on arterial wall in a rat femoral artery vasospasm model.


METHODS
Thirty two animals were divided into four groups: vasospasm without any treatment (group A), vasospasm +250 IU/kg rhEPO group (group B), vasospasm +500 IU/kg rhEPO group (group C), and control group (group D). Rat femoral artery vasospasm model was used. For groups B and C, 7 days of 250 IU/kg and 500 IU/kg intraperitoneal rhEPO in 0.3 ml saline were administered respectively; and for groups A and D, 0.3 ml saline were administered intraperitoneally without any treatment. After 7 days, histological and morphometric analyses were carried out.


RESULTS
Vasospasm alone group demonstrated the highest vessel wall thicknesses, comparing to other groups (p < 0.001). While for groups B and C, vessel wall thickness values were significantly higher than the control group (p < 0.001), between these two groups, there was no significant difference achieved (p > 0.05).


CONCLUSIONS
In our study, there was no significant difference between the two rhEPO treatment groups, but rhEPO treatment was shown to be histologically and morphometrically effective in vasospasm. However, if dosage of EPO treatment is augmented, successful results may be achieved.
Ulusal
Ismail
I
Department of Neurosurgery, Haseki Training and Research Hospital, Istanbul, Turkey.
Tari
Rabia
R
Ozturk
Gulsah
G
Aycicek
Ezgi
E
Aktar
Fadime
F
Kotil
Kadir
K
Bilge
Turgay
T
Kiriş
Talat
T
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D004921:Erythropoietin / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D007274:Injections, Intraperitoneal / Q000379:methods; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000473:pathology*
D004921:Erythropoietin