Quantitative Evaluation of the Neuroprotective Effects of Thiopental Sodium, Propofol, and Halothane on Brain Ischemia in the Gerbil: Effects of the Anesthetics on Ischemic Depolarization and Extracellular Glutamate Concentration

Abstract

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P<0.05, vs. thiopental), and 5.1 (P<0.05) minutes, respectively. Durations of ischemic depolarization were equally reduced in the thiopental and propofol groups compared with that in the halothane group. Severity of neuronal damage with identical duration of ischemic depolarization was attenuated by thiopental compared with the effect of propofol. Maximum glutamate concentrations in the thiopental and propofol group were significantly reduced compared with that in the halothane groups but were comparable. By using P50, we found that the neuroprotective effect of thiopental was greater than that of propofol. Although duration of ischemic depolarization was equally reduced in thiopental and propofol groups, thiopental has a greater suppressive effect on neuronal injury during identical duration of ischemic depolarization than propofol does. Glutamate concentration during brain ischemia tended to be attenuated more by thiopental than by propofol, but it was not statistically significant.

Anesthesia in Experimental Stroke Research

“…Numerous anesthetics have been tested to delay the time to depolarization, because their inhibitory effect on CMR is expected to slow ATP depletion in ischemic tissue. Using either in vivo or in vitro preparations, lidocaine [52], thiopental [53], pentobarbital [54], propofol [55], isoflurane [56], desflurane [57], and sevoflurane [58] have all been reported to delay depolarization onset.…”

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

“…Recent studies showed that propofol improves neurological outcome and decreases infarct size in animal models of cerebral ischemia [5,6]. Several hypotheses about this neuroprotective properties of propofol are: scavenging free radicals derived from the lipid peroxidative reaction [7][8][9]; up-regulation of GABA A -mediated inhibition of synaptic transmission and suppression of glutamate release in cerebral ventricles [10][11][12]; and inhibition of N-methyl-Daspartate (NMDA) receptor and Ca 2? overload [13,14].…”

Expression of CCL2 and CCR2 in the hippocampus and the interventional roles of propofol in rat cerebral ischemia/reperfusion

“…The neuroprotective effect of propofol is the result of a number of mechanisms, including reducing the brain oxygen metabolism rate, removing the oxygen free radicals (12,13), activating the c-aminobutyric acid type A receptor (14), inhibiting the glutamate receptors (15), reducing the extracellular glutamate concentration (16) and increasing the glutamic acid salt intake (17) via inhibiting the release of glutamate-dependent Na + channels. In the present study, propofol was shown to significantly downregulate the expression levels of CCL2 and CCR2 in the hippocampal tissues, indicating that propofol may decrease the inflammatory reactions caused by ischemia during reperfusion.…”