TY - JOUR

T1 - A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats

AU - Springborg, Jacob Bertram

AU - Ma, XiaoDong

AU - Rochat, Per

AU - Knudsen, Gitte Moos

AU - Amtorp, Ole

AU - Paulson, Olaf B

AU - Juhler, Marianne

AU - Olsen, Niels Vidiendal

PY - 2002/2

Y1 - 2002/2

N2 - 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.

AB - 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.

KW - Animals

KW - Blood Pressure

KW - Cerebrovascular Circulation

KW - Erythropoietin

KW - Homeostasis

KW - Injections, Subcutaneous

KW - Male

KW - Rats

KW - Rats, Sprague-Dawley

KW - Subarachnoid Hemorrhage

U2 - 10.1038/sj.bjp.0704521

DO - 10.1038/sj.bjp.0704521

M3 - Journal article

C2 - 11834631

VL - 135

SP - 823

EP - 829

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -