title: Striatal stimulation nurtures endogenous neurogenesis and angiogenesis in chronic-phase ischemic stroke rats.
abstract: Deep brain stimulation (DBS) is used to treat a variety of neurological disorders including Parkinson's disease. In this study, we explored the effects of striatal stimulation (SS) in a rat model of chronic-phase ischemic stroke. The stimulation electrode was implanted into the ischemic  penumbra at 1 month after middle cerebral artery occlusion (MCAO) and thereafter continuously delivered SS over a period of 1 week. Rats were evaluated behaviorally coupled with neuroradiological assessment of the infarct volumes using magnetic resonance imaging (MRI) at pre- and post-SS.  The rats with SS showed significant behavioral recovery in the spontaneous activity and limb placement test compared to those without SS. MRI visualized that SS also significantly reduced the infarct volumes compared to that at pre-SS or without SS. Immunohistochemical analyses revealed a  robust neurogenic response in rats that received SS characterized by a stream of proliferating cells from the subventricular zone migrating to and subsequently differentiating into neurons in the ischemic penumbra, which exhibited a significant GDNF upregulation. In tandem with this SS-mediated  neurogenesis, enhanced angiogenesis was also recognized as revealed by a significant increase in VEGF levels in the penumbra. These results provide evidence that SS affords neurorestoration at the chronic phase of stroke by stimulating endogenous neurogenesis and angiogenesis.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry,and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Morimoto
authors.forename: Takao
authors.initials: T
authors.lastname: Yasuhara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kameda
authors.forename: Tanefumi
authors.initials: T
authors.lastname: Baba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuramoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takahashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Meng
authors.forename: Yuan Wen
authors.initials: YW
authors.lastname: Ji
authors.forename: Tomohito
authors.initials: T
authors.lastname: Kadota
authors.forename: Tomoko
authors.initials: T
authors.lastname: Maruo
authors.forename: Kazushi
authors.initials: K
authors.lastname: Kinugasa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shingo
authors.forename: Cesario V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002908:Chronic Disease; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D004566:Electrodes; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D055495:Neurogenesis; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A