Hypoxic preconditioning reduces propofol-induced neuroapoptosis via regulation of Bcl-2 and Bax and downregulation of activated caspase-3 in the hippocampus of neonatal rats.

OBJECTIVE:  Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning (HPC) was previously demonstrated to provide neuroprotection and brain recovery from either acute or chronic neurodegeneration in several cellular and animal models. Therefore, the present study was designed to investigate the protective effects of hypoxic preconditioning on apoptosis caused by propofol in neonatal rats.

METHODS: Propofol (100 mg/kg) was given to 7-day-old (P7) Sprague Dawley pups. Before the propofol injection, hypoxic preconditioning was administered by subjecting rats to five cycles of 10 min of hypoxia (8% O2) and 10 min of normoxia (21% O2), then 2 h of room air. We detected neuronal structure changes and apoptosis by hematoxylin and eosin (HE) staining and TUNEL assay, respectively. Bcl-2, Bax and cleaved-caspase-3 levels were quantified using Western blotting and immunohistochemistry.

RESULT:  After treatment with propofol, Bcl-2 levels decreased and Bax and cleaved-caspase-3 levels increased. However, our results suggest that hypoxic preconditioning could reverse this change. Conclusion: Our results indicate that pretreatment with hypoxic preconditioning prevents propofol-induced neuroapoptosis by increasing the levels of Bcl-2 and decreasing the levels of Bax and cleaved-caspase-3.