Omi inhibition ameliorates neuron apoptosis and neurological deficit after subarachnoid hemorrhage in rats.

BACKGROUND

Subarachnoid hemorrhage (SAH) is a severe neurological emergency, resulting in cognitive impairments and threatening human's health. Currently, SAH has no effective treatment. It is urgent to search for an effective therapy for SAH.

OBJECTIVE

To explore the expression of Omi protein after subarachnoid hemorrhage in rats.

METHODS

SAH rat model was established by injecting blood into the prechiasmatic cistern. Neurological deficit was assessed by detecting neurological deficit scores and brain tissue water contents. Apoptotic cells were evaluated by TUNEL staining and IHC staining. Omi and Cleaved caspase 3 expressions in nerve cells were determined by double staining using IF. Apoptosis-related proteins were measured by Western blotting assay.

RESULTS

SAH rat model was successfully established, showing more apoptotic cells and high neurological deficit scores in SAH rat. In SAH rat model, Omi expression in nerve cells was elevated and the upregulation of Omi mainly occurred in cytoplasm, accompanied by the degradation of XIAP and the increased cleaved caspase 3/9 and cleaved PARP. Once treated with UCF-101, a specific inhibitor of Omi, the increased cell apoptosis, left/right brain moisture contents and neurological deficits were notably reversed in SAH rat brain. Of note, SAH-induced the increases of apoptosis-related protein in nerve cells were also rescued by the administration of UCF-101.

CONCLUSIONS

UCF-101-mediated Omi inhibition decreased the degradation of XIAP and subsequently inhibited the activation of apoptosis-related proteins, decreased nerve cell apoptosis, leading to the improvement on early brain injury in SAH rat. UCF-101-based Omi inhibition may be used to treat SAH with great potential application.