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Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models.
Neuroscience. 2008 Aug 26; 155(3):937-47.N

Abstract

Experimental cerebral ischemia induces a stress response in neuronal and non-neuronal cells. In the present study we aimed to evaluate detailed cellular stress responses and neurodegenerative changes in the retinas in rat focal cerebral ischemia and hypoperfusion models involving invasive vascular manipulations. Independent groups of adult male Wistar rats were subjected to i) transient middle cerebral artery occlusion (tMCAO), ii) permanent middle cerebral artery occlusion (pMCAO), iii) cortical photothrombosis of the sensorimotor cortex using Rose Bengal dye or iv) bilateral common carotid artery occlusion (BCCAO). Rats were killed, and their eyes with the optic nerves enucleated and processed for histology, immunohistochemistry for neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), hypoxia-inducible factor 1alpha (HIF-1alpha), c-fos, alphaB-crystallin, heat shock protein (HSP) 27, HSP60 and HSP70, and detection of DNA defragmentation. The total number of the retinal ganglion cell layer (RGCL) neurons and GFAP-immunoreactive astrocytes located in the nerve fiber layer were estimated using unbiased stereological counting. Our findings indicate that although permanent and transient MCAO does not cause detectable morphological alterations in the retina or optic nerve, it evokes ischemic stress as revealed by HIF-1alpha and HSPs expression in the RGCL neurons and reactive gliosis in 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 with the sham-operated animals. The retinas from the ipsilateral side of the Rose Bengal model showed a significant decrease in the total number of NeuN-positive neurons in the RGCL as compared with the contralateral ones. However, these eyes did not differ between each other in the HSPs and HIF-1alpha expression or in the GFAP-immunoreactivity of the Müller cells. In conclusion, our data suggest differential expression of various HSPs in the retina and possibly their distinct roles in the cerebral ischemia-mediated stress response and neurodegeneration.

Authors+Show Affiliations

Department of Ophthalmology, Institute of Clinical Medicine, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. giedrius.kalesnykas@uku.fiNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18640247

Citation

Kalesnykas, G, et al. "Neurodegeneration and Cellular Stress in the Retina and Optic Nerve in Rat Cerebral Ischemia and Hypoperfusion Models." Neuroscience, vol. 155, no. 3, 2008, pp. 937-47.
Kalesnykas G, Tuulos T, Uusitalo H, et al. Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models. Neuroscience. 2008;155(3):937-47.
Kalesnykas, G., Tuulos, T., Uusitalo, H., & Jolkkonen, J. (2008). Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models. Neuroscience, 155(3), 937-47. https://doi.org/10.1016/j.neuroscience.2008.06.038
Kalesnykas G, et al. Neurodegeneration and Cellular Stress in the Retina and Optic Nerve in Rat Cerebral Ischemia and Hypoperfusion Models. Neuroscience. 2008 Aug 26;155(3):937-47. PubMed PMID: 18640247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models. AU - Kalesnykas,G, AU - Tuulos,T, AU - Uusitalo,H, AU - Jolkkonen,J, Y1 - 2008/06/21/ PY - 2008/01/02/received PY - 2008/06/12/revised PY - 2008/06/12/accepted PY - 2008/7/22/pubmed PY - 2008/12/19/medline PY - 2008/7/22/entrez SP - 937 EP - 47 JF - Neuroscience JO - Neuroscience VL - 155 IS - 3 N2 - Experimental cerebral ischemia induces a stress response in neuronal and non-neuronal cells. In the present study we aimed to evaluate detailed cellular stress responses and neurodegenerative changes in the retinas in rat focal cerebral ischemia and hypoperfusion models involving invasive vascular manipulations. Independent groups of adult male Wistar rats were subjected to i) transient middle cerebral artery occlusion (tMCAO), ii) permanent middle cerebral artery occlusion (pMCAO), iii) cortical photothrombosis of the sensorimotor cortex using Rose Bengal dye or iv) bilateral common carotid artery occlusion (BCCAO). Rats were killed, and their eyes with the optic nerves enucleated and processed for histology, immunohistochemistry for neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), hypoxia-inducible factor 1alpha (HIF-1alpha), c-fos, alphaB-crystallin, heat shock protein (HSP) 27, HSP60 and HSP70, and detection of DNA defragmentation. The total number of the retinal ganglion cell layer (RGCL) neurons and GFAP-immunoreactive astrocytes located in the nerve fiber layer were estimated using unbiased stereological counting. Our findings indicate that although permanent and transient MCAO does not cause detectable morphological alterations in the retina or optic nerve, it evokes ischemic stress as revealed by HIF-1alpha and HSPs expression in the RGCL neurons and reactive gliosis in 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 with the sham-operated animals. The retinas from the ipsilateral side of the Rose Bengal model showed a significant decrease in the total number of NeuN-positive neurons in the RGCL as compared with the contralateral ones. However, these eyes did not differ between each other in the HSPs and HIF-1alpha expression or in the GFAP-immunoreactivity of the Müller cells. In conclusion, our data suggest differential expression of various HSPs in the retina and possibly their distinct roles in the cerebral ischemia-mediated stress response and neurodegeneration. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18640247/Neurodegeneration_and_cellular_stress_in_the_retina_and_optic_nerve_in_rat_cerebral_ischemia_and_hypoperfusion_models_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(08)00906-8 DB - PRIME DP - Unbound Medicine ER -