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In the present study we have combined the simultaneous inhibition of glutamate uptake and mitochondrial electron transport chain to simulate neuronal damage associated with brain ischemia. Results show that cerebellar granule neurons are not vulnerable to transient glutamate uptake inhibition by L\u2010\n                    <jats:italic>trans<\/jats:italic>\n                    \u2010pyrrolidine\u20102,4\u2010dicarboxylate (PDC) despite the increase in the extracellular concentration of glutamate, unless they are simultaneously exposed to the mitochondrial toxins 3\u2010nitropropionic acid (3\u2010NP) or sodium azide. Cell damage was assessed by light microscopy observation, by reduction of 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide (MTT), and by the fluorescent markers for live and dead cells, calcein and ethidium homodimer, respectively. The protective effect of alternative energy substrates, such as pyruvate, acetoacetate, and \u03b2\u2010hydroxybutyrate against PDC\u2010induced neuronal death during 3\u2010NP exposure was studied and compared to the effects of the antioxidant vitamin E, the spin trapper \u03b1\u2010phenyl\u2010N\u2010\n                    <jats:italic>tert<\/jats:italic>\n                    \u2010butylnitrone (PBN), voltage\u2010dependent calcium channel antagonists, and glutamate receptor antagonists. Results show that neuronal damage can be efficiently prevented in the presence of pyruvate and the N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor antagonist MK\u2010801, whereas the non\u2010NMDA receptor antagonist NBQX, acetoacetate, vitamin E, and PBN showed partial protection. In contrast, \u03b2\u2010hydroxybutyrate and voltage\u2010dependent calcium channels blockers did not show any protective effect at the concentrations tested. J. Neurosci. Res. 64:418\u2013428, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jnr.1093","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T16:13:04Z","timestamp":1030291984000},"page":"418-428","source":"Crossref","is-referenced-by-count":34,"title":["Strategies for neuroprotection against L\u2010\n                    <i>trans<\/i>\n                    \u20102,4\u2010pyrrolidine dicarboxylate\u2010induced neuronal damage during energy impairment in 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