Open AccessComorbid Rat Model of Ischemia and β‐Amyloid Toxicity: Striatal and Cortical Degeneration
Author(s) -
Amtul Zareen,
Whitehead Shawn N.,
Keeley Robin J.,
Bechberger John,
Fisher Alicia L.,
McDonald Robert J.,
Naus Christian C.,
Munoz David G.,
Cechetto David F.
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12149
Subject(s) - striatum , pathology , neuroscience , amyloid (mycology) , medicine , ischemia , cerebral cortex , microglia , toxicity , psychology , inflammation , dopamine
Levels of cerebral amyloid, presumably β‐amyloid ( A beta), toxicity and the incidence of cortical and subcortical ischemia increases with age. However, little is known about the severe pathological condition and dementia that occur as a result of the comorbid occurrence of this vascular risk factor and A beta toxicity. Clinical studies have indicated that small ischemic lesions in the striatum are particularly important in generating dementia in combination with minor amyloid lesions. These cognitive deficits are highly likely to be caused by changes in the cortex. In this study, we examined the viability and morphological changes in microglial and neuronal cells, gap junction proteins (connexin43) and neuritic/axonal retraction ( F er K inase) in the striatum and cerebral cortex using a comorbid rat model of striatal injections of endothelin‐1 ( ET 1) and A beta toxicity. The results demonstrated ventricular enlargement, striatal atrophy, substantial increases in β‐amyloid, ramified microglia and increases in neuritic retraction in the combined models of stroke and A beta toxicity. Changes in connexin43 occurred equally in both groups of A beta‐treated rats, with and without focal ischemia. Although previous behavioral tests demonstrated impairment in memory and learning, the visual discrimination radial maze task did not show significant difference, suggesting the cognitive impairment in these models is not related to damage to the dorsolateral striatum. These results suggest an insight into the relationship between cortical/striatal atrophy, pathology and functional impairment.