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A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats
Author(s) -
Springborg Jacob Bertram,
Ma XiaoDong,
Rochat Per,
Knudsen Gitte Moos,
Amtorp Ole,
Paulson Olaf B,
Juhler Marianne,
Olsen Niels Vidiendal
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704521
Subject(s) - medicine , autoregulation , erythropoietin , cerebral blood flow , anesthesia , blood pressure , subarachnoid hemorrhage , cerebral autoregulation , cisterna magna , intracranial pressure , blood flow , cerebrospinal fluid
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.British Journal of Pharmacology (2002) 135 , 823–829; doi: 10.1038/sj.bjp.0704521