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G. Kalesnykas, T. Tuulos, H. Uusitalo, J. Jolkkonen; Cellular Stress and Neurodegeneration in the Retina and Optic Nerve in Rat Cerebral Ischemia Models. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6123.
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To evaluate detailed cellular stress responses and neurodegenerative changes in the retinas following focal and global cerebral ischemia in rats.
Adult male Wistar rats were operated for permanent and transient middle cerebral artery occlusion (MCAO), cortical photothrombosis of the sensorimotor cortex using Rose Bengal dye or for bilateral common carotid artery occlusion (BCCAO). After 5-10 days rats were sacrificed, eyes together with the optic nerves enucleated and processed for histology, immunohistochemistry for NeuN, glial fibrillary acidic protein (GFAP), hypoxia-inducible factor (HIF) 1α, c-fos, αB-crystallin, HSP27, HSP60 and HSP70, and detection of DNA defragmentation. The total number of the retinal ganglion cell layer (RGCL) neurons and astrocytes located in the nerve fiber layer were estimated using unbiased stereological counting.
Our findings indicate that although permanent and transient MCAO do not cause detectable morphological alterations in the retina or optic nerve, it evokes ischemic stress as revealed by HIF-1α and HSPs expression and reactive gliosis of the Müller cells. Severe neurodegenerative changes in the retina and optic nerve of the BCCAO rats are accompanied by a significant increase in immunoreactivities for the c-fos, HSP27 and HSP70 as compared to the control animals. The retinas from the ipsilateral side of the cortical photothrombosis model showed a significant decrease in the total number of NeuN-positive neurons in the RGCL as compared to the contralateral ones. However, these eyes did not differ between each other neither in the HIF-1α and HSPs expression nor in the GFAP immunoreactivity of the Müller cells which was negative.
1) The BCCAO rats have been used to study cerebral hypoperfusion and related cognitive dysfunctions using Morris water-maze and 8-arm radial maze test in previous studies. Our results suggest that BCCAO rats should be tested using non-visual learning paradigms (e.g. object recognition). 2) Our data suggests differential expression of various HSPs and possibly their distinct roles in the ischemia-mediated stress response.
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