Ischemic brain damage in mice after selectively modifying BDNF or NT4 geneexpression

The neurotrophins and the tyrosine kinase (Trk) B receptor may play a prote ctive 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 f ilament middle cerebral artery occlusion model. Mice lacking both alleles f or neurotrophin-4 (nt4(-/-)) or deficient in a single allele for brain-deri ved neurotrophic factor (bdnf(+/-)) exhibited larger cerebral infarcts comp ared to wildtype inbred 129/SVjae mice (68% and 91%, respectively, compared to controls). Moreover, lesions were larger (21%) in nt4(-/-) mice after p ermanent middle cerebral artery occlusion. Hence, expression of both NT4 an d BDNF, and by inference the TrkB receptor, confers resistance to ischemic injury.