Propofol exerts hippocampal neuron protective effects via up-regulation of metallothionein-3

Abstract

Propofol is an intravenous anesthetic with neuroprotective effects against cerebral ischemia or hypoxia injury. However, the underlying mechanisms remain obscure. Recent years emerging evidence has demonstrated that metallothionein-3 (MT-3), a growth inhibitory factor that exists mainly in the central nervous system, exhibited neuroprotective effect in vivo. Here, we used a model of hypoxia/re-oxygenation (H/R) injury to examine the hippocampal neuroprotective effect of propofol, and explored the role of MT-3 in this action. H/R resulted in reduced cell viability and increased cell death in hippocampal neuron culture, as indicated by MTT assay and lactate dehydrogenase (LDH) release assay, respectively. Pretreatment of propofol at different concentrations (50, 150, and 250 μmol/L) reversed H/R-induced neurotoxicity and increased MT-3 mRNA and protein expressions. Moreover, propofol failed to exert neuroprotective effect when MT-3 was silenced by the transfection with the specific siRNA, suggesting that MT-3 was the crucial mediator for propofol's neuroprotective effect against H/R. In conclusion, our findings showed that propofol is neuroprotective in H/R model on hippocampal neuron cells and that it may act by up-regulation of MT-3.

Hippocampal Neuron Protecting Effect of Propofol Against Hypoxia/Reoxygenation via Inducing Nerve Growth Factor

“…Recently, a growing number of evidences have demonstrated that propofol improved learning and spatial memory functions [11,12], indicating that hippocampus is one of the target structures of propofol in brain. This has been further confirmed by in vivo studies showing that propofol was able to attenuate hippocampal neuron death and promote neurogenesis after oxygen deprivation or cerebral ischemia [4,13]. Consistent with these findings, the present study, revealed a significant increase in hippocampal neuron cell survival during H/R after pretreatment with 50 μM propofol.…”

Total intravenous anesthesia will supercede inhalational anesthesia in pediatric anesthetic practice

“…Propofol may also exert neuroprotective effects following oxygen deprivation, cerebral ischemia, and traumatic brain injury. Animal studies demonstrate that propofol significantly reduces hypoxia‐mediated increases in lactate dehydrogenase, decreases morphological signs of cell damage, and increases neurogenesis . The reduction in ED, as described, may also be exerted through a neuroprotective effect .…”

Angiotensin II-induced mouse hippocampal neuronal HT22 cell apoptosis was inhibited by propofol: Role of neuronal nitric oxide synthase and metallothinonein-3

“…1c, d). 208 Then, we focused on the protective property of propofol, 209 and observed that the Ang II-induced apoptosis was (He et al, 2013). Consistently, we observed that Ang II (p < 0.01, n = 5), which was reversed by propofol pre- (by about 52.1 ± 3.6%, p < 0.01, n = 5) and cIAP-1 292 (by about 62.2 ± 3.4%, p < 0.01, n = 5) (Fig.…”