A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats.
Systemic administration of recombinant erythropoietin (EPO) has been demonstrated to mediate neuroprotection. This effect of EPO may in part rely on a beneficial effect on cerebrovascular dysfunction leading to ischaemic neuronal damage. We investigated the in vivo effects of subcutaneously administered recombinant EPO on impaired cerebral blood flow (CBF) autoregulation after experimental subarachnoid haemorrhage (SAH). Four groups of male Sprague-Dawley rats were studied: group A, sham operation plus vehicle; group B, sham operation plus EPO; group C, SAH plus vehicle; group D, SAH plus EPO. SAH was induced by injection of 0.07 ml of autologous blood into the cisterna magna. EPO (400 iu kg(-1) s.c.) or vehicle was given immediately after the subarachnoid injection of blood or saline. Forty-eight hours after the induction of SAH, CBF autoregulatory function was evaluated using the intracarotid (133)Xe method. CBF autoregulation was preserved in both sham-operated groups (lower limits of mean arterial blood pressure: 91+/-3 and 98+/-3 mmHg in groups A and B, respectively). In the vehicle treated SAH-group, autoregulation was abolished and the relationship between CBF and blood pressure was best described by a single linear regression line. A subcutaneous injection of EPO given immediately after the induction of SAH normalized autoregulation of CBF (lower limit in group D: 93+/-4 mmHg, NS compared with groups A and B). Early activation of endothelial EPO receptors may represent a potential therapeutic strategy in the treatment of cerebrovascular perturbations after SAH.
Springborg
Jacob Bertram
JB
Department of Neuroanaesthesia, The Neuroscience Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Ma
XiaoDong
X
Rochat
Per
P
Knudsen
Gitte Moos
GM
Amtorp
Ole
O
Paulson
Olaf B
OB
Juhler
Marianne
M
Olsen
Niels Vidiendal
NV
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage*; D006706:Homeostasis / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology
D004921:Erythropoietin