J Korean Neurosurg Soc.  2020 Mar;63(2):163-170. 10.3340/jkns.2019.0188.

Milk Fat Globule-Epidermal Growth Factor VIII Ameliorates Brain Injury in the Subacute Phase of Cerebral Ischemia in an Animal Model

Affiliations
  • 1Department of Neurosurgery, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
  • 2Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University, Seoul, Korea
  • 3NEXEL Co., Ltd., Seoul, Korea
  • 4Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea
  • 5Center of Innovative Cell Therapy and Research, Anam Hospital, College of Medicine, Korea University, Seoul, Korea

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.

Keyword

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