Artikel
Neuroprotection by erythropoetin and darbopoetin-alfa – Following experimental intracerebral hemorrhage
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Veröffentlicht: | 30. Mai 2008 |
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Objective: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, we have found that erythropoietin (EPO), administered in its recombinant form (rHuEPO) provides remarkable benefit in several models of brain and spinal cord damage.
Methods: In this study we investigated the neuroprotective effects of EPO and its long-lasting derivative (Darbepoetin-alfa) in a experimental ICH model in the rat. Using these drugs, we asked whether a rHuEPO daily dose (1000 UI/kg-bw, i.v.) or a Darbepoetin-alfa weekly dose (10 µg/kg-bw iv), administered 5 minutes after ICH induction, provides any benefit as assessed by neurological outcome and histopathological investigations.
Male Wistar rats were anesthetized by an intramuscular injection of ketamine and placed in a stereotactic frame. A burr hole was performed by using a microdrill under microscopic control. A 30-gauge needle was introduced into the right striatum (3 mm lateral to midline, 1 mm anterior to bregma, depth 3.5 mm below the surface of the skull) and 10µL of autologous blood, taken from the tail vein, injected over 1 minute. All animals were sacrificed 15 days after ICH was induced.
Results: Treatment with rHuEPO and Darbepoetin-alfa largely prevented neurological deterioration and reduced neuronal damage as compared with saline-treated animals. Mean hemorrhage volume was also significantly decreased in ICH + rHuEPO and Darbepoetin-alfa groups as compared to saline.
Conclusions: This study provides evidence that treatment with rHuEPO and its long-lasting derivative may be a beneficial therapeutic approach to reduce post-ICH morbidity.