Nitric oxide is involved in anoxic preconditioning neuroprotection in rat hippocampal slices

Sublethal anoxia/ischemia protects against subsequent damaging insults in i ntact brain or hippocampal slices. To help further understand mechanisms un derlying anoxic/ischemic preconditioning, we tested three hypotheses which were that: (a) anoxic preconditioning (APC) improves electrical recovery in rat hippocampal slices; (b) anoxic preconditioning requires nitric oxide ( NO); and (c) anoxic preconditioning blocks mitochondrial dysfunction that o ccurs following re-oxygenation after anoxia. Control hippocampal slices und erwent a single 'test' anoxic insult. Experimental slices were precondition ed by 3 short anoxic insults prior to the 'test' insult. Evoked potentials (EPs), and NADH redox status were recorded prior to, during and after preco nditioning and/or 'test' anoxic insults. To examine the role of NO, studies sought to determine whether APC could be produced by the NO donor, DEA/NO, and whether APC could be inhibited by NO synthase (NOS) inhibitor (7-nitro indazole). EP amplitudes recovered significantly better after reoxygenation in preconditioned slices and after NO-emulated preconditioning (90.0 +/- 1 7.7% and 90.0 +/- 21.3%, respectively, n = 9, ** p < 0.01, vs. 17.0 +/- 7.9 %, n = 9, in control slices). Inhibition of NOS blocked APC protection (6.8 +/- 6.8%, n = 9). The intensity of NADH hyperoxidation was not significant ly different among groups following 'test' anoxia. These data confirm that preconditioning by anoxia improves electrical recovery after anoxia in hipp ocampal slices. Evidence supports that NO from constitutive hippocampal NOS may be involved in the neuroprotection afforded by preconditioning by a me chanism that does not change the apparent mitochondrial hyperoxidation afte r anoxia. (C) 1999 Elsevier Science B.V. All rights reserved.