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

研究成果: 雜誌貢獻文章同行評審

42 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)668-676
期刊Journal of Cerebral Blood Flow and Metabolism
出版狀態已發佈 - 4月 2014

ASJC Scopus subject areas

  • 神經內科
  • 神經病學(臨床)
  • 心臟病學與心血管醫學


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