Netrin-1 alleviates subarachnoid haemorrhage-induced brain injury via the PPARγ/NF-KB signalling pathway.

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 C57BL/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 gamma, Bcl-2, Bax and nuclear factor-kappa B (NF-kappa B) were detected by Western blot. Small interfering RNA specific to NTN-1 receptor, UNC5B, and a selective PPAR gamma 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 gamma and Bcl-2 expression and decreased the levels of Bax and NF-kappa B. However, the neuroprotection of NTN-1 was abolished by UNC5B and BADGE. In conclusion, our results demonstrated that NTN-1 attenuates early brain injury following SAH via the UNC5B PPAR gamma/NF-kappa B signalling pathway.