Stroke damage in mice after knocking the neutrophin-4 gene into the brain-derived neurotrophic factor locus.
Neurotrophins play a protective role during cerebral ischemia, and mice lacking both alleles for neurotrophin 4 (Nt4-/- ) or deficient in a single allele for brain-derived neurotrophic factor (Bdnf+/-) have increased susceptibility to cerebral ischemia. This study directly compared the biologic activities of brain-derived neurotrophic factor (BDNF) and NT4 by replacing the coding sequence with the Nt4 sequence (Bdnf +/nt4-ki ). Mice expressing one allele in place of develop 61% bigger lesions after 1-hour middle cerebral artery occlusion compared with wild-type littermates. Physiologic parameters did not contribute to ischemia susceptibility. In conclusion, NT4 is less potent than BDNF in promoting brain survival after stroke.
Endres
Matthias
M
Department of Neurology, Charité Hospital, Humboldt-University, Berlin, Germany. matthias.endres@charite.de
Fan
Guoping
G
Hirt
Lorenz
L
Jaenisch
Rudolf
R
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002544:Cerebral Infarction / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology; D020521:Stroke / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C073922:neurotrophin 4