rhIGF-1 reduces the permeability of the blood-brain barrier following intracerebral hemorrhage in mice

Derek Sunil Nowrangi, Devin W McBride, Anatol Manaenko, Brandon Dixon, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticle

Abstract

Disruption of the blood-brain barrier results in the formation of edema and contributes to the loss of neurological function following intracerebral hemorrhage (ICH). This study examined insulin-like growth factor-1 (IGF-1) as a treatment and its mechanism of action for protecting the blood-brain barrier after ICH in mice. 171 Male CD-1 mice were subjected to ICH via collagenase or autologous blood. A dose study for recombinant human IGF-1 (rhIGF-1) was performed. Brain water content and behavioral deficits were evaluated at 24 and 72 h after the surgery, and Evans blue extravasation and hemoglobin assay were conducted at 24 h. Western blotting was performed for the mechanism study and interventions were used targeting the IGF-1R/GSK3β/MEKK1 pathway. rhIGF-1 reduced edema and blood-brain barrier permeability, and improved neurobehavior outcomes. Western blots showed that rhIGF-1 reduced p-GSK3β and MEKK1 expression, thereby increasing occludin and claudin-5 expression. Inhibition and knockdown of IGF-1R reversed the therapeutic benefits of rhIGF-1. The findings within suggest that stimulation of the IGF-1R is a therapeutic target for ICH which may lead to improved neurofunctional and blood-brain barrier protection.

Original languageEnglish
Pages (from-to)72-81
Number of pages10
JournalExperimental Neurology
Volume312
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

Fingerprint

Cerebral Hemorrhage
Blood-Brain Barrier
Insulin-Like Growth Factor I
Permeability
Somatomedins
Edema
Claudin-5
Western Blotting
Occludin
Evans Blue
Collagenases
Hemoglobins
Water
Brain
Therapeutics

Keywords

  • Blood-brain barrier
  • Blood-injection
  • Collagenase
  • Insulin-like growth factor 1
  • Insulin-like growth factor 1 receptor
  • Intracerebral hemorrhage
  • Intranasal

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

rhIGF-1 reduces the permeability of the blood-brain barrier following intracerebral hemorrhage in mice. / Nowrangi, Derek Sunil; McBride, Devin W; Manaenko, Anatol; Dixon, Brandon; Tang, Jiping; Zhang, John H.

In: Experimental Neurology, Vol. 312, 01.02.2019, p. 72-81.

Research output: Contribution to journalArticle

Nowrangi, Derek Sunil ; McBride, Devin W ; Manaenko, Anatol ; Dixon, Brandon ; Tang, Jiping ; Zhang, John H. / rhIGF-1 reduces the permeability of the blood-brain barrier following intracerebral hemorrhage in mice. In: Experimental Neurology. 2019 ; Vol. 312. pp. 72-81.
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