Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Milk Fat Globule-Epidermal Growth Factor VIII Ameliorates Brain Injury in the Subacute Phase of Cerebral Ischemia in an Animal Model

  • Choi, Jong-Il (Department of Neurosurgery, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Kang, Ho-Young (Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University) ;
  • Han, Choongseong (NEXEL Co., Ltd.) ;
  • Woo, Dong-Hun (NEXEL Co., Ltd.) ;
  • Kim, Jong-Hoon (Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Park, Dong-Hyuk (Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University)
  • Received : 2019.09.11
  • Accepted : 2019.12.01
  • Published : 2020.03.01
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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 periinfarcted 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.

Keywords

References

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