Stroke damage in mice after knocking the neutrophin-4 gene into the brain-derived neurotrophic factor locus

Abstract

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 Bdnf coding sequence with the Nt4 sequence (Bdnf^+/nt4-ki). Mice expressing one Nt4 allele in place of Bdnf 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.