Nitric oxide is involved in anoxic preconditioning neuroprotection in rat hippocampal slices.
Sublethal anoxia/ischemia protects against subsequent damaging insults in intact brain or hippocampal slices. To help further understand mechanisms underlying 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 occurs following re-oxygenation after anoxia. Control hippocampal slices underwent a single 'test' anoxic insult. Experimental slices were preconditioned by 3 short anoxic insults prior to the 'test' insult. Evoked potentials (EPs), and NADH redox status were recorded prior to, during and after preconditioning 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-nitroindazole). EP amplitudes recovered significantly better after reoxygenation in preconditioned slices and after NO-emulated preconditioning (90.0+/-17.7% 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 significantly different among groups following 'test' anoxia. These data confirm that preconditioning by anoxia improves electrical recovery after anoxia in hippocampal slices. Evidence supports that NO from constitutive hippocampal NOS may be involved in the neuroprotection afforded by preconditioning by a mechanism that does not change the apparent mitochondrial hyperoxidation after anoxia.
Department of Neurology, D4-5, University of Miami School of Medicine, P.O. Box 016960, Miami, FL, 33101, USA.
J M
JM
Centeno
M
M
Orti
J B
JB
Salom
T J
TJ
Sick
M A
MA
Pérez-Pinzón
D000818:Animals; D006624:Hippocampus / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D008297:Male; D009243:NAD / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology
D018696:Neuroprotective Agents; D009243:NAD; D009569:Nitric Oxide