Neuronal injury in NCX3 knockout mice following permanent focal cerebral ischemia and in NCX3 knockout cortical neuronal cultures following oxygen-glucose deprivation and glutamate exposure
[en] In this study we subjected NCX3 knockout and wildtype mice to permanent focal cerebral ischemia by intraluminal middle cerebral artery occlusion. Analysis of brain sections by 2,3,5-Triphenyl-2H-tetrazolium chloride staining, 12 hours after middle cerebral artery occlusion revealed no difference in infarct volume between NCX3 knockout and wildtype mice. In addition, we evaluated the effect of NCX3 protein knockdowri on neuronal viability in primary cortical neuronal cultures following in vitro ischemia (oxygen-glucose deprivation) and L-glutamate (glutamate) exposure. In vitro experiments revealed that neuronal viability was higher in NCX3 knockout neuronal cultures than in the wildtype cultures following ischemic and glutamate insults. The reduced sensitivity of neurons from NCX3 knockout mice to in vitro ischemia and excitotoxicity indicates that NCX3 calcium entry mode activity contributes to calcium overload and neuronal death. However our in vivo finding of e lack of differential sensitivity on infarct volume in NCX3 knockout and wildtype mice suggests that any benefit of reduced NCX3 activity is overridden following permanent focal cerebral ischemia. Taken together, these f]ndings suggest that reduced NXC3 activity limits calcium neurotoxicity during severe transient, but not during severe sustained ischemic insults. These results have important implications for the development of the NCX3 protein as a therapeutic target to reduce ischemic brain injury
Cross, J. L.; University of Western Australia and Australian Neuromuscular Research Institute
Meloni, B. P.; University of Western Australia and Australian Neuromuscular Research Institute
Bakker, A. J.; University of Western Australia and School Biomedical and chemical Sciences
Sokolow, S.; University of California, Los Angeles - UCLA
Herchuelz, A.; Université Libre de Bruxelles - ULB > Laboratory of Pharmacology and Therapeutics
Schurmans, Stéphane ; Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire
Knuckey, N. W.; University of Western Australia and Australian Neuromuscular Research Institute
Language :
English
Title :
Neuronal injury in NCX3 knockout mice following permanent focal cerebral ischemia and in NCX3 knockout cortical neuronal cultures following oxygen-glucose deprivation and glutamate exposure
Publication date :
2009
Journal title :
Journal of Experimental Stroke and Translational Medicine
ISSN :
1939-067X
Publisher :
Society for Experimental Stroke, United States - Maryland
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