Neuronal NADPH-d/NOS expression in the nodose ganglion of severe hypoxic rats with or without mild hypoxic preconditioning

This study aimed to test the hypothesis that mild hypoxic preconditioning (MHPC)-induced NOS expression would attenuate the neuropathological changes in the nodose ganglion (NG) of severe hypoxic exposure (SHE) rats. Thus, the young adult rats were caged in the altitude chamber for 4 weeks prior to SHE for 4 h to gain hypoxic preconditioning. The altitude chamber was used to set the height at the level from 5500 m (0.50 atm; pO2 = 79 Torr) to 10,000 m (0.27 atm; pO2 = 43 Torr) for MHPC and SHE, respectively. The experimental animals were allowed to survive for 0, 7, 14, 30 and 60 successive days, respectively. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to detect NADPH-d/nNOS reactivity in the NG at various time points following hypoxic exposure. The present results showed that about 38% of the neurons in the NG displayed NADPH-d/nNOS positive [NADPH-d/nNOS(+)] in normoxic rats. In SHE rats, a peak in the percentage (71%) and staining intensity (230%) of NADPH-d/nNOS(+) nodose neurons at 0 day, which then gradually decreased at 7-60 days. About 25% of the nodose neurons died 60 days after SHE. However, in MHPC rats subjected to SHE, NADPH-d/nNOS(+) neurons peaked in the percentage (51%) and staining intensity (171%) at 0 day, which then decreased at 7-60 days. In addition, neuronal survival was markedly increased by MHPC. These results suggested that MHPC might have a neuroprotective effect that reduces the susceptibility of the nodose neurons to NOS mediated neuropathy subsequent to SHE.