title: Delayed neurovascular dysfunction is alleviated by hydrogen in asphyxiated newborn pigs.
abstract: BACKGROUND
  The neurovascular unit encompasses the functional interactions of cerebrovascular and brain parenchymal cells necessary for the metabolic homeostasis of neurons. Previous studies indicated marked but only transient (1-4 h) reactive oxygen species-dependent neurovascular dysfunction in newborn pigs after severe hypoxic/ischemic (H/I) stress contributing to the neuronal injury after birth asphyxia.
  
  
  OBJECTIVE
  Our major purpose was to determine if neurovascular dysfunction would also occur later, at 24 h after a milder H/I stress. We also tested if the putative hydroxyl radical scavenger hydrogen (H2) exerted neurovascular protection.
  
  
  METHODS
  Anesthetized, ventilated piglets were assigned to three groups of 9 animals: time control, asphyxia/reventilation with air, and asphyxia/reventilation with air +2.1% H2 for 4 h. Asphyxia was induced by suspending ventilation for 8 min. Cerebrovascular reactivity (CR) of pial arterioles was determined using closed cranial window/intravital microscopy 24 h after asphyxia to the endothelium-dependent cerebrovascular stimulus hypercapnia, the neuronal function-dependent stimulus N-methyl-D-aspartate (NMDA), norepinephrine, and sodium nitroprusside. The brains were subjected to histopathology.
  
  
  RESULTS
  Hemodynamic parameters, blood gases, and core temperature did not differ significantly among the experimental groups. In the early reventilation period, the recovery of electroencephalographic activity was significantly better in H2-treated animals. Asphyxia/reventilation severely attenuated CR to hypercapnia and NMDA; however, reactivity to norepinephrine and sodium nitroprusside were unaltered. H2 fully or partially preserved CR to hypercapnia or NMDA, respectively. Histopathology revealed modest neuroprotection afforded by H2.
  
  
  CONCLUSIONS
  Severe stimulus-selective delayed neurovascular dysfunction develops and persists even after mild H/I stress. H2 alleviates this delayed neurovascular dysfunction that can contribute to its neuroprotective effect.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary. olah.orsolya @ med.u-szeged.hu
authors.forename: Orsolya
authors.initials: O
authors.lastname: Oláh
authors.forename: Valéria
authors.initials: V
authors.lastname: Tóth-Szűki
authors.forename: Péter
authors.initials: P
authors.lastname: Temesvári
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bari
authors.forename: Ferenc
authors.initials: F
authors.lastname: Domoki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001784:Blood Gas Analysis; D058256:Brain Waves / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006859:Hydrogen / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D006935:Hypercapnia / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020127:Recovery of Function; D012121:Respiration, Artificial; D013552:Swine; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D017665:Hydroxyl Radical; D006859:Hydrogen