Milk fat globule-epidermal growth factor VIII ameliorates brain injury in the subacute phase of cerebral ischemia in an animal model

Jong Il Choi, Ho Young Kang, Choongseong Han, Dong Hun Woo, Jong Hoon Kim, Dong Hyuk Park

Research output: Contribution to journalArticle

Abstract

Objective: Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods: Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results: Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the peri-infarcted brain region, and significantly higher numbers of BrdU-and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion: Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

Original languageEnglish
JournalJournal of Korean Neurosurgical Society
Volume63
Issue number2-163 170
DOIs
Publication statusPublished - 2020 Jan 1

Keywords

  • Angiogenesis
  • infarction
  • Inflammation
  • MFG-E8
  • Neurobehavioral outcome
  • Neuronal proliferation
  • Subacute cerebral

ASJC Scopus subject areas

  • Surgery
  • Neuroscience(all)
  • Clinical Neurology

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