A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy

Mol Neurobiol. 2024 Mar;61(3):1417-1432. doi: 10.1007/s12035-023-03645-9. Epub 2023 Sep 18.

Abstract

Reperfusion is an essential pathological stage in hypoxic ischemic encephalopathy (HIE). Although the Rice-Vannucci model is widely used in HIE research, it remains difficult to replicate HIE-related reperfusion brain injury. The purpose of this study is to establish a rat model of hypoxia ischemia reperfusion brain damage (HIRBD) using a common carotid artery (CCA) muscle bridge in order to investigate the mechanisms of cerebral resistance to hypoxic-ischemic and reperfusion brain damage. Random assignment of Sprague-Dawley (SD) rats to the Sham, HIRBD, and Rice-Vannucci groups. Changes in body weight, mortality rate, spontaneous alternation behavior test (SAB test), and dynamic changes in cerebral blood flow (CBF) were detected. The damaged cerebral cortices were extracted for morphological comparison, transcriptomic analysis, and quantitative real-time PCR. Harvesting the hippocampus for transmission electron microscopy (TEM) detection. As a result, CCA muscle bridge could effectively block CBF, which recovered after the muscle bridge detachment. Pathological comparison, the SAB test, and TEM analysis revealed that brain damage in Rice-Vannucci was more severe than HIRBD. Gpx1, S100a6, Cldn5, Esr1, and Gfap were highly expressed in both HIRBD and Rice-Vannucci. In conclusion, the CCA muscle bridge-established HIRBD model could be used as an innovative and dependable model to simulate pathological process of HIRBD.

Keywords: Hypoxic ischemia reperfusion brain damage (HIRBD); Hypoxic ischemic encephalopathy (HIE); Mechanisms; Model; Rice-Vannucci.

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / pathology
  • Brain Injuries* / pathology
  • Hypoxia / pathology
  • Hypoxia-Ischemia, Brain* / complications
  • Hypoxia-Ischemia, Brain* / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion
  • Reperfusion Injury* / complications
  • Reperfusion Injury* / pathology