Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression

Abstract

The neurotrophins and the tyrosine kinase (Trk) B receptor may play a protective role in the pathophysiology of cerebral ischemia. In this study, the authors investigated whether reducing endogenous expression of TrkB- binding neurotrophins modifies the susceptibility to ischemic injury after 1- hour middle cerebral artery occlusion followed by 23 hours of reperfusion in a filament middle cerebral artery occlusion model. Mice lacking both alleles for neurotrophin-4 (nt4^-1-) or deficient in a single allele for brain- derived neurotrophic factor (bdnf+/-) exhibited larger cerebral infarcts compared to wild-type inbred 129/SV(jae) mice (68% and 91%, respectively, compared to controls). Moreover, lesions were larger (21%) in nt4(-/-) mice after permanent middle cerebral artery occlusion. Hence, expression of both NT4 and BDNF, and by inference the TrkB receptor, confers resistance to ischemic injury.