Cerebral microvascular damage occurs early after hypoxia-ischemia via nNOS activation in the neonatal brain

Yi Ching Hsu, Ying Chao Chang, Yung Chieh Lin, Chun I. Sze, Chao Ching Huang, Chien Jung Ho

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Microvascular injury early after hypoxic ischemia (HI) may contribute to neonatal brain damage. N-methyl-D-aspartate receptor overstimulation activates neuronal nitric oxide synthases (nNOS). We hypothesized that microvascular damage occurs early post-HI via nNOS activation and contributes to brain injury. Postpartum day-7 rat pups were treated with 7-nitroindazole (7-NI) or aminoguanidine (AG) before or after HI. Electron microscopy was performed to measure neuronal and endothelial cell damage. There were vascular lumen narrowing at 1 hour, pyknotic neurons at 3 hours, and extensive neuronal damage and loss of vessels at 24 hours post HI. Early after reoxygenation, there were neurons with heterochromatic chromatin and endothelial cells with enlarged nuclei occluding the lumen. There was also increased 3-nitrotyrosin in the microvessels and decreased cerebral blood perfusion. 7-NI and AG treatment before hypoxia provided complete and partial neuroprotection, respectively. Early post-reoxygenation, the AG group showed significantly increased microvascular nitrosative stress, microvascular interruptions, swollen nuclei that narrowed the vascular lumen, and decreased cerebral perfusion. The 7-NI group showed significantly decreased microvascular nitrosative stress, patent vascular lumen, and increased cerebral perfusion. Our results indicate that microvascular damage occurs early and progressively post HI. Neuronal nitric oxide synthases activation contributes to microvascular damage and decreased cerebral perfusion early after reoxygenation and worsens brain damage.

Original languageEnglish
Pages (from-to)668-676
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number4
DOIs
Publication statusPublished - 2014

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Nitric Oxide Synthase Type I
Ischemia
Perfusion
Brain
Blood Vessels
Endothelial Cells
Neurons
Microvessels
N-Methyl-D-Aspartate Receptors
Brain Injuries
Postpartum Period
Chromatin
Electron Microscopy
Hypoxia
Wounds and Injuries
7-nitroindazole
pimagedine

Keywords

  • Cerebral blood flow
  • Hypoxic ischemia
  • Microvessel
  • Neonatal brain
  • nNOS

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Cerebral microvascular damage occurs early after hypoxia-ischemia via nNOS activation in the neonatal brain. / Hsu, Yi Ching; Chang, Ying Chao; Lin, Yung Chieh; Sze, Chun I.; Huang, Chao Ching; Ho, Chien Jung.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 34, No. 4, 2014, p. 668-676.

Research output: Contribution to journalArticle

Hsu, Yi Ching ; Chang, Ying Chao ; Lin, Yung Chieh ; Sze, Chun I. ; Huang, Chao Ching ; Ho, Chien Jung. / Cerebral microvascular damage occurs early after hypoxia-ischemia via nNOS activation in the neonatal brain. In: Journal of Cerebral Blood Flow and Metabolism. 2014 ; Vol. 34, No. 4. pp. 668-676.
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