Noggin protects against ischemic brain injury in rodents.
OBJECTIVE
Bone morphogenetic proteins and their receptors are expressed in adult brains, and their expression levels increase after cerebral ischemia. The brain also expresses an inhibitor of bone morphogenetic protein signaling, noggin, but the role of noggin in ischemic disease outcome has not been studied.


METHODS
We used transgenic mice overexpressing noggin to assess whether inhibition of bone morphogenetic protein signaling affects ischemic injury responses after permanent middle cerebral artery occlusion.


RESULTS
Transgenic mice overexpressing noggin mice had significantly smaller infarct volumes and lower motor deficits compared to wild-type mice. CD11b(+) and IBA1(+) microglia along with oligodendroglial progenitors were significantly increased in transgenic mice overexpressing noggin mice at 14 days after permanent middle cerebral artery occlusion.


CONCLUSIONS
These results provide genetic evidence that overexpression of noggin reduces ischemic brain injury after permanent middle cerebral artery occlusion via enhanced activation of microglia and oligodendrogenesis.
Samanta
Jayshree
J
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Ill, USA.
Alden
Tord
T
Gobeske
Kevin
K
Kan
Lixin
L
Kessler
John A
JA
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002545:Brain Ischemia / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D002352:Carrier Proteins / Q000235:genetics*; D049109:Cell Proliferation; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism; D010291:Paresis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D020127:Recovery of Function / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein