Ischemic Brain Damage in Mice after Selectively Modifying BDNF or NT4 Gene Expression

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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−/−) or deficient in a single allele for brain-derived neurotrophic factor ( bdnf+/−) exhibited larger cerebral infarcts compared to wild-type inbred 129/SVjae 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.