In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 23, No. 3 ( 2019-03), p. 2256-2262
Abstract:
Netrin‐1 ( NTN ‐1) is a novel drug to alleviate early brain injury following subarachnoid haemorrhage ( SAH ). However the molecular mechanism of NTN ‐1‐mediated protection against early brain injury following SAH remains largely elusive. This study aims to evaluate the effects and mechanisms of NTN ‐1 in protecting SAH ‐induced early brain injury. The endovascular perforation SAH model was constructed using male C57 BL /6J mice, and recombinant NTN ‐1 was administrated intravenously. Mortality rates, SAH grade, brain water content, neurological score and neuronal apoptosis were evaluated. The expression of PPAR γ, Bcl‐2, Bax and nuclear factor‐kappa B ( NF ‐κB) were detected by Western blot. Small interfering RNA specific to NTN ‐1 receptor, UNC 5B, and a selective PPAR γ antagonist, bisphenol A diglycidyl ether ( BADGE ), were applied in combination with NTN ‐1. The results suggested that NTN ‐1 improved the neurological deficits, reduced the brain water content and alleviated neuronal apoptosis. In addition, NTN ‐1 enhanced PPAR γ and Bcl‐2 expression and decreased the levels of Bax and NF ‐κB. However, the neuroprotection of NTN ‐1 was abolished by UNC 5B and BADGE . In conclusion, our results demonstrated that NTN ‐1 attenuates early brain injury following SAH via the UNC 5B PPAR γ/ NF ‐κB signalling pathway.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2019.23.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2076114-4
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