title: Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.
abstract: OBJECTIVE
  Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion.
  
  
  METHODS
  Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury.
  
  
  RESULTS
  Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration.
  
  
  CONCLUSIONS
  White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Bo-Ryoung
authors.initials: BR
authors.lastname: Choi
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Bin
authors.initials: DB
authors.lastname: Back
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chung Hwan
authors.initials: CH
authors.lastname: Kang
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Moon
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Choi
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoung Ja
authors.initials: KJ
authors.lastname: Kwon
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Seol-Heui
authors.initials: SH
authors.lastname: Han
authors.affiliation: From the Department of Neurology (B.-R.C., D.B.B., K.J.K., S.-H.H., H.Y.K.), Department of Biological Sciences (B.-R.C., D.-H.K., J.-S.H.), Department of Radiology (C.H.K., W.-J.M.), Department of Medicine (D.-H.C.), Department of Pharmacology (C.Y.S.), and Department of Rehabilitation Medicine (B.-R.K., J.L.), Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea. hykimmd@gmail.com.
authors.forename: Hahn Young
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D000077407:Cilostazol; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation; D056784:Leukoencephalopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004676:Myelin Basic Protein / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009483:Neuropsychological Tests; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011901:Ranvier's Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology; D066127:White Matter / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; D013777:Tetrazoles; D000077407:Cilostazol
keywords: cilostazol; dementia, vascular; models, animal; white matter