Ghrelin inhibits early brain injury due to subarachnoid hemorrhage via the Tim-3-mediated HMGB1/NF-κB pathway.

OBJECTIVE

To explore the protective effect of Ghrelin on EBI caused by SAH through the HMGB1/NF-κB pathway mediated by Tim-3.

METHODS

Rats were divided into four groups (n = 6): Sham group (Sham), SAH+vehicle group (SAH), SAH + 0.02 μg/kg rhGhrelin group (rhGhrelin-L), SAH + 0.04 μg/kg rhGhrelin group (rhGhrelin-H). At 48 h after SAH, the behavioral impairment in rats was examined for using neurobehavioral scores. The pathological change in the temporal basal brain tissue was observed by HE, and the expression of GHSR-1α and Tim-3 in the temporal basal brain tissue was observed by Western blot. To further validate that rhGhrelin could inhibit SAH-induced EBI by the Tim-3-mediated HMGB1/NF-κB pathway, we treated rats with the AAV-Tim-3. The contents of the inflammatory factors IL-1β, TNF-α, IL-6 was determined by ELISA, apoptosis was detected by TUNEL, the neurons were visualized by Nissl staining, the expression of GHSR-1α，Tim-3, HMGB1, RAGE, NF-κB p65 was determined by Western blot.

RESULTS

Compared with the SAH group, rats treated with rhGhrelin had a significantly lower neurobehavioral score, significantly decreased inflammatory factors IL-1β, TNF-α, IL-6 expression, significantly decreased apoptosis index, and significantly decreased Tim-3, HMGB1, RAGE, NF-κB p65 expression(p < 0.01). The protective effect of rhGhrelin on the SAH-induced EBI was reversed by the AAV-Tim-3.

CONCLUSION

Ghrelin has beneficial effects against SAH-induced EBI by inhibiting the HMGB1/NF-κB pathway, which may be regulated by Tim-3.