) observed neuroprotective synergy in between MK-801 and also the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD.FMK) on both infarct size and therapeutic window. The mixture of antiexcitotoxic approaches with thrombolysis has also been shown to provide additive protection within a rodent model of embolic stroke (52). On theoretical grounds, antioxidant drugs may well be specially worthwhile in reducing reperfusion-induced injury, by way of example in association with thrombolytic therapy, or the deleterious element of particular development aspect actions.Acknowledgments This operate was supported by a Pfizer postdoctoral fellowship (J.-M. Lee), National Analysis Service Award grant 1 F32 NS10926-01 (G.J. Zipfel), and National Institute of Neurological Issues and Stroke grant NS 32636 (D.W. Choi).1. Choi, D.W. 1988. Glutamate neurotoxicity and ailments of the nervous program. Neuron. 1:62334. two. Albers, G.W., Goldberg, M.P., and Choi, D.W. 1989. N-methyl-D-aspartate antagonists: prepared for clinical trial in brain ischemia Ann. Neurol. 25:39803. 3. Buchan, A.M. 1990. Do NMDA antagonists protect against cerebral ischemia: are clinical trials warranted Cerebrovasc. Brain Metab. Rev. 2:16.four. Lee, J.M., Zipfel, G.J., and Choi, D.W. 1999. The altering landscape of ischaemic brain injury mechanisms. Nature. 399:A7 14. 5. Kerchner, G.A., Canzoniero, L.M.T., Yu, S.P., Ling, C., and Choi, D.W. 2000. Zinc current is mediated by voltage-gated calcium channels and enhanced by extracellular acidity in mouse cortical neurons. J. Physiol. In press. 6. Obrenovitch, T.P., and Richards, D.A. 1995. Extracellular neurotransmitter adjustments in cerebral ischaemia. Cerebrovasc.Tolvaptan Brain Metab. Rev. 7:14. 7. Von Lubitz, D. 1999. Adenosine and cerebral ischemia: therapeutic future or death of a brave idea Eur. J. Pharmacol. 15:95. eight. Behrens, M.M., Strasser, U., Lobner, D., and Dugan, L.L. 1999. Neurotrophin-mediated potentiation of neuronal injury. Microsc. Res. Tech. 45:27684. 9. Frederickson, C.J. 1989. Neurobiology of zinc and zinc-containing neurons. Int. Rev. Neurobiol. 31:14538. 10. Choi, D.W., and Koh, J.Y. 1998. Zinc and brain injury. Annu. Rev. Neurosci. 21:34775. 11. Tonder, N., Johansen, F.F., Frederickson, C.J., Zimmer, J., and Diemer, N.H. 1990. Doable part of zinc within the selective degeneration of dentate hilar neurons after cerebral ischemia within the adult rat.Fludarabine Neurosci.PMID:23849184 Lett. 109:24752. 12. Kaczmarek, L.K. 1987. The role of protein kinase C in the regulation of ion channels and neurotransmitter release. Trends Neurosci. ten:304. 13. Hara, H., Onodera, H., Yoshidomi, M., Matsuda, Y., and Kogure, K. 1990. Staurosporine, a novel protein kinase C inhibitor, prevents postischemic neuronal damage in the gerbil and rat. J. Cereb. Blood Flow Metab. ten:64653. 14. Nakane, H., et al. 1998. Protein kinase C modulates ischemia-induced amino acids release in the striatum of hypertensive rats. Brain Res. 782:29096. 15. Cohen, P. 1997. The look for physiological substrates of MAP and SAP kinases in mammalian cells. Trends Cell Biol. 7:35361. 16. Sugino, T., Nozaki, K., and Hashimoto, N. 2000. Activation of mitogenactivated protein kinases in gerbil hippocampus with ischemic tolerance induced by 3-nitropropionic acid. Neurosci. Lett. 278:10104. 17. Alessandrini, A., Namura, S., Moskowitz, M.A., and Bonventre, J.V. 1999. MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proc. Natl. Acad. Sci. USA. 96:128662869. 18.
