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Crit Care Med. 2004 Sep;32(9 Suppl):S359-65.

Effects of intracerebroventricular application of brain-derived neurotrophic factor on cerebral recovery after cardiac arrest in rats.

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Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.



After transient global cerebral ischemia, selective vulnerable brain areas show delayed neurodegeneration with characteristics of apoptosis. Recent data demonstrate potent neuroprotective effects of the application of endogenous growth hormones such as brain-derived neurotrophic factor (BDNF) after focal cerebral ischemia. To assess possible effects of the intracerebroventricular application of BDNF on cerebral recovery after global cerebral ischemia due to cardiac arrest in rats, various selective vulnerable brain areas were investigated.


Global cerebral ischemia was initiated by ventricular fibrillation in rats under general anesthesia. After 6 mins, the animals were resuscitated by external cardiac massage combined with defibrillation and divided into two groups (BDNF vs. placebo). BDNF or placebo (1 microg/hr) was applied continuously during the complete reperfusion time using an implanted osmotic minipump. After 6 hrs, 24 hrs, 3 days, and 7 days (n = 6-7 per group), coronal brain sections were analyzed by terminal deoxynucleotidyltransferase-mediated d-uracil triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining and a caspase activity assay in the hippocampal cornu ammonis 1 sector, the nucleus reticularis thalami, and the striatum. At 24 hrs, 3 days, and 7 days, animals were tested according to a neurologic deficit score.


In all groups, typical delayed neurodegeneration was observed in selective vulnerable brain areas. Neuroscore, TUNEL, and Nissl staining revealed no relevant differences between the groups (BDNF vs. placebo) with regard to neurologic recovery and the number of viable (after 7 days in cornu ammonis 1 sector: BDNF, 110 +/- 32; placebo, 142 +/- 53) and TUNEL-positive neurons (after 7 days in cornu ammonis 1 sector: BDNF, 360 +/- 81; placebo, 253 +/- 62) during the different time points.


Despite the well-known neuroprotective properties of BDNF in ischemic-induced neuronal degeneration, the present study did not reveal any beneficial effects regarding neurologic recovery and neurohistopathologic outcome after global cerebral ischemia in rats. Future investigations should focus on intracellular signaling cascades activated by BDNF after global cerebral ischemia.

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