Semaphorin 6A improves functional recovery in conjunction with motor training after cerebral ischemia.
We have previously identified Semaphorin 6a (Sema6A) as an upregulated gene product in a gene expression screen in cortical ischemia [1]. Semaphorin 6a was regulated during the recovery phase following ischemia in the cortex. Semaphorin 6a is a member of the superfamily of semaphorins involved in axon guidance and other functions. We hypothesized that the upregulation indicates a crucial role of this molecule in post-stroke rewiring of the brain. Here we have tested this hypothesis by overexpressing semaphorin 6a in the cortex by microinjection of a modified AAV2-virus. A circumscribed cortical infarct was induced, and the recovery of rats monitored for up to 4 weeks using a well-established test battery (accelerated rotarod training paradigm, cylinder test, adhesive tape removal). We observed a significant improvement in post-ischemic recovery of animals injected with the semaphorin 6a virus versus animals treated with a control virus. We conclude that semaphorin 6a overexpressed in the cortex enhances recovery after cerebral ischemia. Semaphorin 6a may represent a novel therapeutic candidate for the treatment of chronic stroke.
Rogalewski
Andreas
A
Department of Neurology, University of Muenster, Muenster, Germany.
Dittgen
Tanjew
T
Klugmann
Matthias
M
Kirsch
Friederike
F
Krüger
Carola
C
Pitzer
Claudia
C
Minnerup
Jens
J
Schäbitz
Wolf-Rüdiger
WR
Schneider
Armin
A
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics; D006801:Humans; D009043:Motor Activity / Q000502:physiology*; D010805:Physical Conditioning, Animal; D011597:Psychomotor Performance; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D039961:Semaphorins / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology
C551905:Sema6A protein, rat; D039961:Semaphorins