scholarly journals The pro-survival pathways of mTOR and protein kinase B target glycogen synthase kinase-3β and nuclear factor-κB to foster endogenous microglial cell protection

2007 ◽  
Author(s):  
Zhao Chong ◽  
Faqi Li ◽  
Kenneth Maiese
Keyword(s):  
Protein Kinase ◽  
Microglial Cell ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Nuclear Factor Κb ◽  
Glycogen Synthase Kinase ◽  
Nuclear Factor ◽  
Glycogen Synthase Kinase 3Β ◽  
Cell Protection ◽  
Survival Pathways

scholarly journals Noxious Stimulation Attenuates Ketamine-induced Neuroapoptosis in the Developing Rat Brain

2012 ◽  
Vol 117 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Jia-Ren Liu ◽  
Qian Liu ◽  
Jing Li ◽  
Chongwha Baek ◽  
Xiao Hui Han ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Glycogen Synthase Kinase ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Noxious Stimulation ◽  
Glycogen Synthase Kinase 3Β ◽  
Rat Pups

Background Ketamine induces neuroapoptosis in neonatal rodents. However, these experimental paradigms were performed without concurrent noxious stimulation, a condition that does not reflect the interaction of anesthesia and surgical stimulation. Noxious stimulation with and without concurrent analgesic drugs has been shown to have divergent patterns of neuronal activation and cell death. We hypothesized that concurrent noxious stimulation would attenuate ketamine-induced caspase-3 activation. Methods Postnatal day 7 Sprague-Dawley rat pups were randomized to a 6-h exposure to ketamine with and without peripheral noxious stimulation by intraplantar injection of complete Freund's adjuvant. A cohort of naïve rat pups with and without complete Freund's adjuvant injections served as control subjects. Neuroapoptosis was measured by cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining. In order to determine if concurrent noxious simulation altered the expression of cell survival and cell cycle proteins, levels of protein kinase B and glycogen synthase kinase-3β and cyclin D1 were measured. Results Ketamine induced a significant increase in cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining with increases in cyclin D1 levels. Concurrent noxious stimulation with ketamine attenuated caspase-3 activation and maintained cyclin D1 levels. Phosphorylation of protein kinase B and glycogen synthase kinase-3β was not definitively altered under these conditions. Conclusion The administration of ketamine with concurrent noxious stimulation results in the attenuation of the neuroapoptotic response. These findings suggest that concurrent surgery and procedural pain attenuates ketamine-induced neuroapoptosis.

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