An in vitro study of the neuroprotective effect of propofol on hypoxic hippocampal slice.

PRIMARY OBJECTIVE: To determine whether propofol has a neuroprotective effect on hypoxic brain injury. RESEARCH DESIGN: A hippocampal slice, in artificial cerebrospinal fluid (ASCF) with glucose and oxygen deprivation (OGD), was used as an in vitro model for brain hypoxia. METHODS AND PROCEDURES: The orthodromic population spike (OPS) and hypoxic injury potentia1 (HIP) were recorded in the CA1 region when Schaffer collateral was stimulated in the CA3 region of the hippocampal slices during hypoxia. The concentrations of amino acid neurotransmitters in perfusion solution of hippocampal slices were directly measured using high performance liquid chromatography (HPLC). Morphological changes of neurons, astrocytes and mitochondria in CA1 region were observed using histology and electron microscopy. Neuronal apoptosis was evaluated with TUNEL assay. MAIN OUTCOME AND RESULTS: Propofol treatment delayed the elimination of OPS and improved the recovery of OPS; decreased frequency of HIP, postponed the onset of HIP and increased the duration of HIP. Propofol treatment also decreased the release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but elevated the release of γ-aminobutyric acid (GABA). Morphological studies showed that propofol treatment attenuated oedema of pyramid neurons in the CA1 region and reduced apoptosis. CONCLUSIONS: Propofol has a neuro-protective effect on hippocampal neuron injury induced by hypoxia.

[Effects of intrathecal injection of U0126 on the expression of phospho-CREB in spinal cord of morphine-induced withdrawal rats].

AIM: To explore effects of intrathecal injection of U0126 on morphine withdrawal response and the spinal Phospho-CREB expression in morphine-induced withdrawal rats. METHODS: All the rats were divided into 5 groups: control group, dependence group, withdrawal group, U0126 group (5 microg, it) and DMSO group. Morphine withdrawal score, touch evoked agitation scores(TEA score), immunohistochemical and Western-blotting technique were used to evaluate morphine withdrawal response and the expression of Phospho-CREB in the spinal cord. RESULTS: Intrathecal injection of MEK inhibitor U0126 significantly alleviated morphine withdrawal symptoms. Morphine withdrawal scores in U0126 group (22.5 +/- 4.09) were significantly lower than that of withdrawal group (28.6 +/- 4.89, P < 0.05). TEA score of withdrawal group was 13.5 +/- 2.55, which was significantly higher than that of U0126 group (10.0 +/- 2.76, P < 0.05). Phospho-CREB positive neurons in the spinal dorsal horn of withdrawal group were 380 +/- 71, which is higher than that of U0126 group (293 +/- 47, P < 0.05). Compared with withdrawal group, level of Phospho-CREB protein detected by Western blot in spinal cord of U0126 group was significantly lower. CONCLUSION: MEK inhibitors U0126 could suppress expression of Phospho-CREB in the spinal cord.