Resumo

Introduction Studies in laboratory animals have shown that anesthetic agents reduce infarct size and improve neurologic outcome after transient focal and incomplete hemispheric ischemia (Gelb and cols, 2002). Propofol (2,6-diisopropylphenol) is an intravenous sedative– hypnotic agent commonly used in anesthesia and intensive care that has been tested as a neuroprotective agent in models of cerebral ischemia. Both positive ( Velly and cols, 2003) and negative (Qi and cols, 2002; Feiner and cols, 2005) results have emerged from in vitro studies. This current study evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen deprivation and low glucose (ODLG). Methods: Experimental Animal Ethics Committee: 4201092005-6. The neuroprotective effects of propofol were evaluated in rat organotypic hippocampal slices exposed to ODLG, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action were used the following pharmacological tools: tetrodotoxin (TTX), EGTA and ù conotoxin MVIIC. After ODLG insult, cell viabilility in hippocampal slices was assessed by fluorescence microscopy using the ethidium homodimer. Results: In all concentrations tested (1-300 ìM), propofol was able to reduce neuronal death in the CA1 region of the hippocampus. The maximum effect of propofol in neuronal death reduction (47,02±1,47%) was obtained with the concentration of 100 ìM. Imaging of CA1 region of rat hippocampal slices subject to ischemic insult treated with TTX, propofol and propofol with TTX showed a decrease in cell death that amounted to 35,60±2,84%, 25,58±2.11% and 43,30±3.62%, respectively. Cell protection effect was also observed when the slices subject to ischemic insult treated with EGTA (38,70±0,37%), propofol (33,67±3,95%) and both drugs (44,02±3,04%). In addition, rat hippocampal slices subject to ischemic insult treated with ù conotoxin MVIIC , propofol and both drugs showed a decrease in cell death that amounted to 32,84±1,19%, 31,54±1,66% and 44,05±0,32%, respectively. Discussion: This results indicate that propofol neuroprotection seems to be dependent on the influx of Na+ through the Na+ ion channels sensible to voltage and extracellular Ca2+ influx. ù conotoxin MVIIC and propofol presented additional effects regarding neuroprotection indicating that neuroprotetion by propofol could be independent of blocking voltage-dependent -N and -P/Q type Ca2+ channels. Therefore, this study suggests that propofol presents neuroprotector effects in hippocampus slices submitted to deprivation of glucose and oxigen. The mechanism of this neuroprotection seems to involve the reduction of the neuronal Na+ and Ca2+ influx independent of -N, -P/Q type Ca2+ channels.