Effects of lithium chloride on isoflurane-induced neuroapoptosis in neonatal rat hippocampus
- Author:
Li-Ping MIAO
1
Author Information
- Publication Type:Journal Article
- Keywords: Apoptosis; Collapsin response mediator protein-2; Glycogen synthase kinase-3β; Isoflurane; Lithium chloride
- From: Chinese Pharmaceutical Journal 2016;51(22):1923-1928
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To investigate the effects of lithium chloride (LiCl) on neuroapoptosis in hippocampus induced by isoflurane and the relationships with GSK-3β/CRMP2 pathway in neonatal rats. METHODS: Sixty neonatal rats at postnatal day 7 were assigned randomly into air + NS group, air + LiCl group, Iso + NS group, Iso + LiCl2, Iso + LiCl4 and Iso + LiCl8 group. Rats in groups of air + NS and air + LiCl were exposed to air for 6 h. Rats in groups of Iso + NS, Iso + LiCl2, Iso + LiCl4 and Iso + LiCl8 were exposed to 0.75% isoflurane for 6 h. Rats in groups of Air + NS and Iso + NS were injectedintracerebroventricularlywith NS 5 μL separately 30 min before exposure to air or isoflurane. Rats in groups of air + LiCl, Iso + LiCl2, Iso + LiCl4 and Iso + LiCl8 were injected intracerebroventricularly with LiCl 5 μL separately 30 min before exposureto air or isoflurane. Rats in groups of Iso + LiCl2, Iso + LiCl4, Iso + LiCl8 and Air + LiCl were injected intracerebroventricularly with LiCl5 μL separately 30 min before exposure with the different concentrations(20, 40, 80, 80 mmol·L-1, respectively). At the end of exposure, the hippocampus of some rats were separated and proteins expression of cleaved caspase-3, phospho-GSK-3β(p-GSK-3β), GSK-3β, phospho-CRMP2 (p-CRMP2) and CRMP2 were detected by Western blot (n=5); other rats were perfused and their brain were embedded by paraffin 2 h after exposure, the neuroapoptosis in the hippocampus CA1 area was detected by TUNEL staining (n=5). RESULTS: Lithium chloride (80 mmol·L-1) significantly decreased the cleaved caspase-3 levels(P < 0.01) induced by isoflurane in hippocampus of neonatal rats. TUNEL positive cells in CA1 area were significantly decreased by 41.69%(P < 0.01) in group Iso + LiCl8 when compared with those in group Iso + NS. The protein expressionof p-GSK-3β and p-CRMP2 in group Iso + NS were significantly decreased and increased respectivelycompared to those in group air + NS. The ratio of p-GSK-3β/GSK-3β and p-CRMP2/CRMP2 in the hippocampal increased 41.03% (P < 0.05) and decreased 23.64%(P < 0.05) respectively in Iso + LiCl8 group when compared with Iso + NS group. CONCLUSION: Lithium chloride attenuates isoflurane-induced neurodegeneration through inhibiting hippocampal neuroapoptosis in neonatal rats. Inhibition of the activation of GSK-3β/CRMP2 signaling pathways may involve in the mechanisms.
