title: Transplanted bone marrow stromal cells protect neurovascular units and ameliorate brain damage in stroke-prone spontaneously hypertensive rats.
abstract: This study was aimed to assess whether bone marrow stromal cells (BMSC) could ameliorate brain damage when transplanted into the brain of stroke-prone spontaneously hypertensive rats (SHR-SP). The BMSC or vehicle was stereotactically engrafted into the striatum of male SHR-SP at 8 weeks of age. Daily loading with 0.5% NaCl-containing water was started from 9 weeks. MRIs and histological analysis were performed at 11 and 12 weeks, respectively. Wistar-Kyoto rats were employed as the control. As a result, T2-weighted images demonstrated neither cerebral infarct nor intracerebral hemorrhage, but identified abnormal dilatation of the lateral ventricles in SHR-SP. HE staining demonstrated selective neuronal injury in their neocortices. Double fluorescence immunohistochemistry revealed that they had a decreased density of the collagen IV-positive microvessels and a decreased number of the microvessels with normal integrity between basement membrane and astrocyte end-feet. BMSC transplantation significantly ameliorated the ventricular dilatation and the breakdown of neurovascular integrity. These findings strongly suggest that long-lasting hypertension may primarily damage neurovascular integrity and neurons, leading to tissue atrophy and ventricular dilatation prior to the occurrence of cerebral stroke. The BMSC may ameliorate these damaging processes when directly transplanted into the brain, opening the possibility of prophylactic medicine to prevent microvascular and parenchymal-damaging processes in hypertensive patients at higher risk for cerebral stroke.
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Taku
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Maruichi
authors.forename: Masahito
authors.initials: M
authors.lastname: Kawabori
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakayama
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D017072:Neostriatum / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013238:Stereotaxic Techniques; D020521:Stroke / Q000473:pathology* / Q000628:therapy*; D017154:Stromal Cells / Q000637:transplantation*