title: Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats.
abstract: Constraint-induced movement therapy (CIMT) after stroke enhances not only functional reorganization but also structural plasticity of the brain in the adult rats. We examined whether forced limb-use which mimicked CIMT could influence ischemia-induced neurogenesis, apoptosis and behavioral recovery in the aged rats. Aged rats were divided into a sham group, an ischemia group, and an ischemia group with forced limb-use. Focal cerebral ischemia was induced by injection of endothelin-1. Forced limb-use began on post-stroke day 7 by fitting a plaster cast around the unimpaired upper limbs of rats for 3 weeks. Behavioral recovery was evaluated by tapered/ledged beam-walking test on postoperative day 32. The expression of doublecortin, neuronal nuclei, glial fibrillary acidic protein and Iba-1 were measured by single or double immunohistochemistry, and apoptosis was measured by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The production of neuroblasts in the subventricular zone (SVZ) was significantly increased after stroke. Forced limb-use enhanced the proliferation of newborn neurons in the SVZ, as well as increased the long-term survival of newborn neurons. Furthermore, forced limb-use suppressed apoptosis and improved the motor functions after stroke in the aged rats. Forced limb-use exerted few effects on inflammation. Neither the number nor dendritic complexity of newborn granule cells in the hippocampus was affected by forced limb-use. Forced limb-use is effective in enhancing neurogenesis and behavioral recovery after stroke even in the aged rats.
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: H L
authors.initials: HL
authors.lastname: Qu
authors.affiliation: Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: S S
authors.initials: SS
authors.lastname: Zhao
authors.affiliation: Dermatology, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, China.
authors.forename: T
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China; Neurology, Benxi Central Hospital of China Medical University, Benxi, China.
authors.forename: C G
authors.initials: CG
authors.lastname: Song
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Cao
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Jolkkonen
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China. Electronic address: cszhao@mail.cmu.edu.cn.
authors.forename: C S
authors.initials: CS
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000139:chemically induced / Q000473:pathology / Q000534:rehabilitation*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D019332:Endothelin-1; D020547:Lateral Ventricles / Q000473:pathology / Q000503:physiopathology*; D008124:Locomotion; D008297:Male; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology; D026741:Physical Therapy Modalities; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D020521:Stroke / Q000139:chemically induced / Q000473:pathology; D000071939:Stroke Rehabilitation
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D019332:Endothelin-1
keywords: aging; behavioral recovery; forced limb-use; neurogenesis; stroke