title: Hypoxia-induced cellular and vascular changes in the nucleus tractus solitarius and ventrolateral medulla.
abstract: Major changes in arterial pressure, autonomic, and respiratory activity occur in response to hypoxia. We analyzed structural damage and increased vascular permeability in the ventrolateral medulla and nucleus tractus solitarius, which control autonomic, respiratory, and cardiovascular functions in adult Wistar rats subjected to 2 hours of hypoxia (7% oxygen + 93% nitrogen) for up to 14 days after hypoxicexposure. Brainstem tissue levels of vascular endothelial growth factor (VEGF), nitric oxide (NO), and glutamate were significantly increased over control levels after hypoxic injury. By electron microscopy, swollen neurons and dendrites, degenerating axons, disrupted myelin sheaths, and swollen astrocyte processes were observed in the nucleus tractus solitarius and ventrolateral medulla. Leakage of intravenously administered horseradish peroxidase was observed through vascular walls in hypoxic rats. These results suggest that increased VEGF and NO production in hypoxia resulted in increased vascular permeability, which, along with increased levels of glutamate, may have induced structural alterations of the neurons, dendrites, and axons. Administration of the antioxidant neurohormone melatonin (10mg/kg) before and after the hypoxia reduced VEGF, NO, and glutamate levels and improved ultrastructural abnormalities induced by hypoxia exposure, suggesting that it may have a therapeutic potential in reducing hypoxia-associated brainstem damage.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. antkaurc@nus.edu.sg
authors.forename: Charanjit
authors.initials: C
authors.lastname: Kaur
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Viswanathan
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
mesh_terms: D000818:Animals; D018698:Glutamic Acid; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008550:Melatonin / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; C409466:NR1 NMDA receptor; D018091:Receptors, AMPA; D058468:Receptors, Ionotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D008550:Melatonin