Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression.
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.
Endres
M
M
Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Fan
G
G
Hirt
L
L
Fujii
M
M
Matsushita
K
K
Liu
X
X
Jaenisch
R
R
Moskowitz
M A
MA
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000378:metabolism; D002544:Cerebral Infarction / Q000209:etiology; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C073922:neurotrophin 4