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 journalArticlepeer-review

2 Citations (Scopus)

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
Pages (from-to)163-170
Number of pages8
JournalJournal of Korean Neurosurgical Society
Volume63
Issue number2-163 170
DOIs
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This study was supported in part by grants from Korea University (K1809681 and K1912651); the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A2057994); and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C03370400). The funding bodies did not play any role in the design, collection, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.

Publisher Copyright:
© 2020 The Korean Neurosurgical Society.

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • General Neuroscience
  • Clinical Neurology

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