Moreover, in mice overexpressing selleck chemical human UCP 2 gene, brain damage was diminished after experimental stroke and traumatic brain injury, and neurological recovery was enhanced. In rat cultured cortical neurons, overexpression of UCP 2 gene reduced cell death and inhibited caspase 3 activation induced by oxygen and glucose deprivation. It is intriguing that Inhibitors,Modulators,Libraries results from the present study also showed that pretreatment with rosiglitazone increased mitochondrial UCP2 expression, reduced the extent of protein oxidation, O2 overproduction and dys function of mitochondrial respiratory enzyme complex I, hindered the translocation of Bax or cytochrome c between cytosol and mitochondria and reduced neuronal damage in the hippocampal CA3 subfield elicited by ex perimental status epilepticus.
In contrast, treatment with the PPAR�� antagonist, GW9662 exerted opposite effects. Thus, the present study provided a novel demonstration of an antioxidant role for the PPAR�� UCP2 signaling pathway against oxidative Inhibitors,Modulators,Libraries stress and mitochondrial dys functions that reduced neuronal cell injury in the hippo campal CA3 subfield after the experimental Inhibitors,Modulators,Libraries model of temporal lobe status epilepticus. Neuroprotection following prolonged seizures, such as status epilepticus should encompass not only the pre vention of neuronal cell death, but also preservation of neuronal and network function. Less well Inhibitors,Modulators,Libraries studied are the protective mechanisms elicited by seizure activity espe cially under status epilepticus. Except for the detrimental chain reaction under status epilepticus, acute response protein to counteract these detrimental effects may be elicited as an endogenous protective mechanism.
En dogenous neuronal survival mechanisms following pro longed seizure insult are those that have been evolutionarily Inhibitors,Modulators,Libraries conserved and may trigger a number of signaling pathways to exert the protective effect and therefore be strong candidates to imply as therapeutic strategies. In animal studies with status epilepticus, several endogenous protective mechanisms to lessen neuronal damage were proposed, including activation ERK1 2, epileptic tolerance, vascular endothelial growth factor, activation of adenosine A1 receptors, erythropoi etin receptor. Based on real time PCR and west ern blot analyses, we demonstrated a significant increase in UCP2 mRNA in the hippocampal sellckchem CA3 subfield after KA elicited status epilepticus, followed by augmented UCP2 protein levels. In addition, immunofluorescence staining demonstrated that the activated UCP2 was mainly in the mitochondria of hippocampal CA3 neu rons. Thus, our results suggested that mitochondrial UCP2 may play an endogenous neuroprotective role against hippocampal neuronal cell damage under the stress of prolonged epileptic seizures.