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- Title
Marked prevention of ischemic brain injury by Neu2000, an NMDA antagonist and antioxidant derived from aspirin and sulfasalazine.
- Authors
Byoung Joo Gwag; Young Ae Lee; Sun Young Ko; Moon Jung Lee; Doo Soon Im; Bok Sun Yun; Hyang Ran Lim; Sun Mi Park; Han Yeol Byun; Sun Ju Son; Hye Jin Kwon; Ji Yoon Lee; Jae-Young Cho; Seok Joon Won; Kee-Won Kim; Young Min Ahn; Ho Sang Moon; Hae Un Lee; Sung Hwa Yoon; Ji-Hyun Noh
- Abstract
Excitotoxicity and oxidative stress mediate neuronal death after hypoxic–ischemic brain injury. We examined the possibility that targeting both N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity and oxidative stress would result in enhanced neuroprotection against hypoxic–ischemia. 2-Hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000) was derived from aspirin and sulfasalazine to prevent both NMDA neurotoxicity and oxidative stress. In cortical cell cultures, Neu2000 was shown to be an uncompetitive NMDA receptor antagonist and completely blocked free radical toxicity at doses as low as 0.3 μmol/L. Neu2000 showed marked neuroprotection in a masked fashion using histology and behavioral testing in two rodent models of focal cerebral ischemia without causing neurotoxic side effects. Neu2000 protected against the effects of middle cerebral artery occlusion, even when delivered 8 h after reperfusion. Single bolus administration of the drug prevented gray and white matter degeneration and spared neurologic function for over 28 days after MACO. Neu2000 may be a novel therapy for combating both NMDA receptor-mediated excitotoxicity and oxidative stress, the two major routes of neuronal death in ischemia, offering profound neuroprotection and an extended therapeutic window.Journal of Cerebral Blood Flow & Metabolism (2007) 27, 1142–1151; doi:10.1038/sj.jcbfm.9600418; published online 15 November 2006
- Publication
Journal of Cerebral Blood Flow & Metabolism, 2007, Vol 27, Issue 6, p1142
- ISSN
0271-678X
- Publication type
Academic Journal
- DOI
10.1038/sj.jcbfm.9600418