Kynurenate is neuroprotective following experimental brain injury in the rat

作者: Ramona R. Hicks , Douglas H. Smith , Thomas A. Gennarelli , Tracy McIntosh

DOI: 10.1016/0006-8993(94)91601-2

关键词:

摘要: Pharmacologic inhibition of excitatory amino acid neurotransmission improves physiologic, metabolic, and neurobehavioral outcome following experimental brain trauma. However, no studies to date have demonstrated pharmacologically-induced attenuation histopathological changes associated with injury models. The present study examined the effects kynurenate, an NMDA non-NMDA receptor antagonist, on neuronal survival in hippocampus after lateral fluid-percussion rat. Animals (n = 10/treatment) randomly received intravenous injection either kynurenate (300 mg/kg) or buffer (equal volume) 15 min moderate severity. Two weeks injury, animals were sacrificed cell loss was Nissl staining. Selective neurons CA3 region hippocampus, which has previously been characterized this model found be significantly attenuated treatment (P < 0.05). These data suggest that pharmacologic compounds are known beneficial physiological may also attenuate post-traumatic loss. Our results support other recent pharmacological intervention antagonist therapeutic value injury.

参考文章(53)
DW Choi, M Maulucci-Gedde, AR Kriegstein, Glutamate neurotoxicity in cortical cell culture The Journal of Neuroscience. ,vol. 7, pp. 357- 368 ,(1987) , 10.1523/JNEUROSCI.07-02-00357.1987
R.L. HAYES, L.W. JENKINS, B.G. LYETH, R.L. BALSTER, S.E. ROBINSON, G.L. CLIFTON, J.F. STUBBINS, H.F. YOUNG, Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. Journal of Neurotrauma. ,vol. 5, pp. 259- 274 ,(1988) , 10.1089/NEU.1988.5.259
John W. Olney, Madelon T. Price, Lisa Samson, Joann Labruyere, The role of specific ions in glutamate neurotoxicity Neuroscience Letters. ,vol. 65, pp. 65- 71 ,(1986) , 10.1016/0304-3940(86)90121-7
Selina C. Cortez, T.K. McIntosh, L.J. Noble, Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations Brain Research. ,vol. 482, pp. 271- 282 ,(1989) , 10.1016/0006-8993(89)91190-6
Dale Corbett, Suzanne Evans, Charlene Thomas, Dong Wang, Richard A. Jonas, MK-801 reduced cerebral ischemic injury by inducing hypothermia. Brain Research. ,vol. 514, pp. 300- 304 ,(1990) , 10.1016/0006-8993(90)91424-F
Jean R. Wrathall, Jim Bouzoukis, David Choiniere, Effect of kynurenate on functional deficits resulting from traumatic spinal cord injury European Journal of Pharmacology. ,vol. 218, pp. 273- 281 ,(1992) , 10.1016/0014-2999(92)90179-8
R. Schmidt-Kastner, T.F. Freund, Selective vulnerability of the hippocampus in brain ischemia. Neuroscience. ,vol. 40, pp. 599- 636 ,(1991) , 10.1016/0306-4522(91)90001-5