Propofol post-conditioning protects the blood brain barrier by decreasing matrix metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral outcome in a rat model of focal cerebral ischemia-reperfusion injury.

Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by ischemic stroke, protects the brain from ischemia/reperfusion injury and improves neuronal function. However, whether propofol is able to protect the blood brain barrier (BBB) and the underlying mechanisms have remained to be elucidated. In the present study, a rat model of cerebral ischemia/reperfusion was established, using a thread embolism to achieve middle cerebral artery occlusion. Rats were treated with propofol (propofol post-conditioning) or physiological saline (control) administered by intravenous injection 30 min following reperfusion. Twenty-four hours following reperfusion, neurobehavioral manifestations were assessed. The levels of cephaloedema, damage to the BBB and expression levels of matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun N-terminal kinase (pJNK) were determined in order to evaluate the effects of propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group, the levels of brain water content and Evans blue content, as well as the expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the propofol post-conditioning group. These results indicated that propofol post-conditioning improved the neurobehavioral manifestations and attenuated the BBB damage and cephaloedema induced following cerebral ischemia/reperfusion. This effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the concurrent decrease in JNK phosphorylation.

Overexpression of FABP3 promotes apoptosis through inducing mitochondrial impairment in embryonic cancer cells.

Fatty acid-binding protein 3 (FABP3) is a low-molecular-weight protein with a distinct tissue distribution that may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. Previously, we have found that FABP3 was involved in apoptosis-associated congenital cardiac malformations, but the underlying mechanisms have not yet been described. In the present study, we investigated the characteristics of mitochondrial dysfunction in embryonic cancer cells (P19 cells) that overexpressed FABP3. We demonstrated that in FABP3-overexpressing P19 cells a lower cellular ATP production was accompanied by a dramatic decrease in mitochondrial membrane potential (MMP), despite the lack of a substantial decrease in the mtDNA copy number. In addition, FABP3 overexpression also led to an imbalance in mitochondrial dynamics and to excess intracellular reactive oxygen species production. Collectively, our results indicated that overexpression of FABP3 in P19 cells caused mitochondrion dysfunction that might be responsible for the development of FABP3-induced apoptosis.