Effect of age and sex on N-methyl-D-aspartate antagonist-induced neuronal necrosis in rats

Stroke; a Journal of Cerebral Circulation
R N Auer

Abstract

Although N-methyl-D-aspartate (NMDA) antagonism may be a useful therapeutic approach in stroke treatment, it has been found that these pharmacological agents cause neuronal necrosis in restricted cortical regions of the rodent brain. To test the hypothesis that age and sex influence NMDA antagonist-induced neuronal necrosis, male and female rats were studied at 2 months (young), 12 months (middle-aged), and 24 months (old) of age. A dose of 5 mg/kg MK-801 was administered, followed by quantitation of neuronal necrosis at nine coronal levels in the cingulate and retrosplenial cortex at 1 week of survival. Mortality was dependent on age but not sex and was higher in the old rats (P<.01). The number of necrotic neurons per hemisphere was greater in female than in male rats at all ages (P<.0001). Female rats also showed increasing neuronal necrosis with age (P<.05). The results indicate a major sex difference in neuronal cytotoxicity caused by NMDA antagonists and a minor increase in susceptibility with increasing age in females. The findings may be relevant to development of drugs with NMDA antagonist properties for use in human stroke.

References

Mar 1, 1975·British Journal of Anaesthesia·B G Douglas, R Dagirmanjian
Jul 15, 1992·The Journal of Comparative Neurology·S N Reid, J M Juraska
Jul 15, 1992·The Journal of Comparative Neurology·S N Reid, J M Juraska
Apr 1, 1992·Archives of Neurology·G W AlbersD W Choi
Mar 1, 1991·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·E D HallK L Linseman
Dec 1, 1989·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A Kurumaji, J McCulloch
Sep 1, 1989·Clinical Pharmacology and Therapeutics·T WalleE C Conradi
Feb 1, 1987·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M IngvarB K Siesjö
Feb 15, 1985·Biochemical Pharmacology·H KitagawaK Kitani
Jan 1, 1984·Acta Neuropathologica·R N AuerB K Siesjö
Jan 27, 1984·European Journal of Pharmacology·T NabeshimaT Kameyama
Feb 20, 1995·The Journal of Comparative Neurology·S N Reid, J M Juraska
Apr 1, 1994·Neurochemical Research·M SerraG Biggio
Jan 1, 1994·Brain Research Bulletin·M Zanin, R N Takahashi
Aug 20, 1993·Brain Research·D Hönack, W Löscher

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Citations

Jul 2, 2003·Neurotoxicity Research·W ZajaczkowskiL Kaczmarek
Jul 9, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Michal Arad, Ina Weiner
Aug 27, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jon Dickerson, Frank R Sharp
Jun 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·M M AdamsJ H Morrison
Oct 1, 1996·Molecular and Chemical Neuropathology·R N AuerB I Tranmer
Apr 25, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·P D Hurn, I M Macrae
Apr 10, 2007·Epilepsy & Behavior : E&B·Frank R Sharp, Robert L Hendren
Mar 23, 2007·Neurotoxicology and Teratology·L K M WrightM G Paule
Feb 13, 2007·Neurotoxicology and Teratology·L K M WrightM G Paule
Apr 25, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Adrian BuenoJose De Olmos
Jan 6, 2004·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Adrian BuenoJose de Olmos
Aug 28, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Eric PlitmanAriel Graff-Guerrero
May 29, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kanae KurodaYoshinobu Aoki
Sep 20, 2000·Biology of Reproduction·P M Wise, D B Dubal
Jun 28, 2018·Pharmacological Reviews·Panos ZanosTodd D Gould

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