Neuroprotection of Heme Oxygenase-2 in Mice AfterIntracerebral Hemorrhage

J Neuropathol Exp Neurol. 2021 Apr 16;80(5):457-466. doi: 10.1093/jnen/nlab025.

Abstract

There are few effective preventive or therapeutic strategies to mitigate the effects of catastrophic intracerebral hemorrhage (ICH) in humans. Heme oxygenase is the rate-limiting enzyme in heme metabolism; heme oxygenase-2 (HO-2) is a constitutively expressed heme oxygenase. We explored the involvement of HO-2 in a collagenase-induced mouse model of ICH in C57BL/6 wild-type and HO-2 knockout mice. We assessed oxidative stress injury, blood-brain barrier permeability, neuronal damage, late-stage angiogenesis, and hematoma clearance using immunofluorescence, Western blot, MRI, and special staining methods. Our results show that HO-2 reduces brain injury volume and brain edema, alleviates cytotoxic injury, affects vascular function in the early stage of ICH, and improves hematoma absorbance and angiogenesis in the late stage of ICH in this model. Thus, we found that HO-2 has a protective effect on brain injury after ICH.

Keywords: Angiogenesis; Heme oxygenase-2; Intracerebral hemorrhage; Neuronal damage; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain Edema / metabolism
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Cerebral Hemorrhage / metabolism*
  • Disease Models, Animal
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / pathology
  • Neuroprotection / physiology*
  • Permeability

Substances

  • Heme Oxygenase (Decyclizing)
  • heme oxygenase-2