title: Stroke-prone rats exhibit prolonged behavioral deficits without increased brain injury: an indication of disrupted post-stroke brain recovery of function.
abstract: Stroke-prone rat strains exhibit an increased stroke risk and sensitivity, and reduced endogenous mechanisms of ischemic brain tolerance. This experiment provides a comparative, serial evaluation of neurological deficits and brain injury following middle cerebral artery occlusion/permanent focal stroke in this high-risk strain. Stroke-prone spontaneously hypertensive (SHR-SP), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were evaluated over 28 days using magnetic resonance imaging (MRI), histopathology, and neurobehavioral testing. T2- and diffusion weighted-MRI was performed after 1, 10 and 28 days to measure the degree of stroke-induced brain injury. Normotensive WKY rats receiving the same stroke and other SHR-SP rats receiving sham surgery were used for control comparisons. Functional deficits were scored after 1, 4, 11, 18 and 28 days. The degree of brain infarction/injury was practically identical in hypertensive and stroke-prone rats. WKY rats exhibited significantly smaller infarcts (P<0.05), with neurological function recovering quickly to normal by day 11 in this strain. Functional deficits persisted longer in hypertensive rats, with function recovering to normal by day 18 (P<0.05). Functional deficits in SHR-SP rats persisted the longest, and were observed even after 28 days (P<0.05). This increased and prolonged neurologic dysfunction exhibited by SHR-SP compared to SHR rats, while exhibiting practically identical degrees of brain injury/infarction, reflects the increased stroke risk and sensitivity of this strain and suggests a reduced SHR-SP brain plasticity following injury. Therefore, the stroke-prone rat provides an enhanced and prolonged functional deficit model that can be used to elucidate those mechanisms/novel targets critical to longitudinal neurobehavioral recovery post-stroke.
authors.affiliation: Department of Laboratory Animal Science, GlaxoSmithKline, King of Prussia, PA 19406, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Maguire
authors.forename: Robert
authors.initials: R
authors.lastname: Strittmatter
authors.forename: Sudeep
authors.initials: S
authors.lastname: Chandra
authors.forename: Frank C
authors.initials: FC
authors.lastname: Barone
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain; D020520:Brain Infarction / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D004195:Disease Models, Animal; D007839:Functional Laterality; D006973:Hypertension / Q000209:etiology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009068:Movement / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D016548:Prosencephalon / Q000473:pathology / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020127:Recovery of Function; D018709:Statistics, Nonparametric; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors