title: Mild hypoxic preconditioning attenuates injury-induced NADPH-d/nNOS expression in brainstem motor neurons of adult rats.
abstract: Excessive production of nitric oxide (NO) might have detrimental effects on the hypoxia-related neuropathology. This study aimed to test if mild hypoxic preconditioning (MHPC) would attenuate the pathological changes in the brainstem motoneurons having a different functional component after peripheral nerve crush injury (PNCI). Prior to PNCI treatment, young adult rats were caged in the mild hypoxic altitude chamber with 79Torr of the partial oxygen concentration ( pO(2)) (i.e., 0.5atm at 5500m in height) for 4 weeks to adapt the environmental changes. After that, all the animals having successfully crushed both the hypoglossal and vagus nerves (left-side) were allowed to survive for 3, 7, 14, 30 and 60 successive days in normoxic condition. Nicotinamine adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry revealed that MHPC reduces NADPH-d/nNOS expression in the hypoglossal nucleus (HN) and the dorsal motor nucleus of the vagus (DMN) at different time points after PNCI. The morphological findings were further ascertained by Western blot analysis of nNOS and nitrite assay for NO production. Both the morphological and quantitative results peaked at 7 days in HN, whereas for those in DMN were progressively increased up to 60 days following PNCI. The staining intensity of NADPH-d/nNOS(+) neurons, expression of nNOS protein, NO production levels as well as the neuronal loss in HN and DMN of MHPC rats following PNCI were attenuated, especially for those having a longer survival period over 14 days. The MHPC treatment might induce minute amounts of NO to alter the state of milieu of the experimental animals to protect against the PNCI.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, China Medical University, Taichung, Taiwan. ihwei@mail.cmu.edu.tw
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Wei
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Huang
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Tseng
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
authors.forename: Hui-Chin
authors.initials: HC
authors.lastname: Tu
authors.forename: Mang-Hung
authors.initials: MH
authors.lastname: Tsai
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Wen
authors.forename: Jeng-Yung
authors.initials: JY
authors.lastname: Shieh
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001933:Brain Stem / Q000201:enzymology* / Q000503:physiopathology; D006651:Histocytochemistry; D007002:Hypoglossal Nerve / Q000166:cytology / Q000201:enzymology / Q000503:physiopathology; D020437:Hypoglossal Nerve Diseases / Q000201:enzymology / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008297:Male; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology; D009252:NADPH Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D009410:Nerve Degeneration / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000201:enzymology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000201:enzymology / Q000503:physiopathology; D020421:Vagus Nerve Diseases / Q000201:enzymology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase