title: The Role of Endogenous Neurogenesis in Functional Recovery and Motor Map Reorganization Induced by Rehabilitative Therapy after Stroke in Rats.
abstract: OBJECTIVE
  Endogenous neurogenesis is associated with functional recovery after stroke, but the roles it plays in such recovery processes are unknown. This study aims to clarify the roles of endogenous neurogenesis in functional recovery and motor map reorganization induced by rehabilitative therapy after stroke by using a rat model of cerebral ischemia (CI).
  
  
  METHODS
  Ischemia was induced via photothrombosis in the caudal forelimb area of the rat cortex. First, we examined the effect of rehabilitative therapy on functional recovery and motor map reorganization, using the skilled forelimb reaching test and intracortical microstimulation. Next, using the same approaches, we examined how motor map reorganization changed when endogenous neurogenesis after stroke was inhibited by cytosine-β-d-arabinofuranoside (Ara-C).
  
  
  RESULTS
  Rehabilitative therapy for 4 weeks after the induction of stroke significantly improved functional recovery and expanded the rostral forelimb area (RFA). Intraventricular Ara-C administration for 4-10 days after stroke significantly suppressed endogenous neurogenesis compared to vehicle, but did not appear to influence non-neural cells (e.g., microglia, astrocytes, and vascular endothelial cells). Suppressing endogenous neurogenesis via Ara-C administration significantly inhibited (~50% less than vehicle) functional recovery and RFA expansion (~33% of vehicle) induced by rehabilitative therapy after CI.
  
  
  CONCLUSIONS
  After CI, inhibition of endogenous neurogenesis suppressed both the functional and anatomical markers of rehabilitative therapy. These results suggest that endogenous neurogenesis contributes to functional recovery after CI related to rehabilitative therapy, possibly through its promotion of motor map reorganization, although other additional roles cannot be ruled out.
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Stroke Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiromoto
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan. Electronic address: n-okabe@med.kawasaki-m.ac.jp.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Okabe
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Maruyama-Nakamura
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Himi
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Narita
authors.affiliation: Department of Stroke Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yagita
authors.affiliation: Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Second Department of Physiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D008297:Male; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000502:physiology*; D065854:Spatial Navigation / Q000502:physiology*; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*; D000071939:Stroke Rehabilitation; D016896:Treatment Outcome
keywords: Cerebral ischemia; cytosine-β-d-arabinofuranoside (Ara-C); endogenous neurogenesis; motor map reorganization; motor recovery; rehabilitative therapy