| Epileptic seizures can cause both morphological and functional changes within the brain as well as cognitive and neuropsychological alterations. Experimental modeling and clinical neuroimaging of patients has shown that certain seizures are capable of causing neuronal death. Underlining the potential impact of such changes, patients who continue to experience seizures may have associated cognitive impairment, including mental slowness, memory difficulties and attention deficits. In children, cognitive problems are more diffuse, responsible for language troubles, learning difficulties, poor academic outcome, behavior problems and finally unfortunate socio-professional prognosis. However, at present, few effective treatments are available for cognitive impairments in epilepsy.Acupuncture is utilized as a clinical treatment for various diseases in Chinese medicine and possesses many effects such as the promotion of homeostasis, improvement in brain circulation, pain control, and neuromodulatory function in the central nervous system, and also benefited a large number of patients with epileptic seizures clinically from two thousands years ago through nowadays. Previous research proved that EA had a significant anti-convulsive effect in epileptic rats induced either by kainic acid or penicillin, and EA stimulation at proper acupoints improved cognitive deficits in pilocarpine-epileptic rats. Research into cell death after seizures has identified the induction of the molecular machinery of apoptosis. Our previous research also indicated that EA stimulation at Daizhui and Baihui acupoints can prevent neuronal apoptosis in experimental epileptic rats. So it is reasonable to hypothesize that EA pretreatment can prevent cognitive impairment caused by epilepsy, and the biological mechanism may include its anti-apoptosis effect.Neuronal apoptosis may be regulated by a series of apoptosis-regulatory proteins. Caspases are aspartate-specific cysteine proteases present in cells as zymogens that form the active enzyme following proteolytic cleavage. A Caspase cascade is initiated that culminates in activation of'executioner'Caspases, such as Caspase-3, which cleave key intracellular structural and survival proteins and activate the enzyme responsible for the characteristic DNA fragmentation pattern. Bcl-2 family proteins, like Caspases, are involved in regulating seizure-induced neuronal death and can exert anti- or pro-apoptotic effects. Dimerization interactions of Bcl-2 family proteins regulate mitochondrial and other intracellular organelle function.In the present study, morris water maze test was employed to assess spatial discriminative ability per group respectively and to analyze the protective effects of EA,the damaged and surviving neurons in hippocampus were observed by TUNEL and DAPI staining, and the expression of Caspases and Bcl-2 family proteins were detected with immunofluoresence. We provided evidence that EA pretreatment can improve cognitive impairment in epilepsy rats through reducing hippocampus neuronal apoptosis.This study showed:1) SE significantly increased the TUNEL positive neurons in CA1/CA3 region of hippocampus, and induced cognitive impairment of rats (P<0.01, n=5).2) EA pretreatment at Baihui and Dazhui acupoints decreased the total number of apoptotic neuronal death in CA1/CA3 region of hippocampus, and improved SE induced cognitive impairment (P< 0.05, n=5).3) EA pretreatment at Baihui and Dazhui acupoints suppressed the SE induced over-expression of pro-apoptotic protein Bim, Bid, and Bax (P<0.05, n=5).4) The expression of anti-apoptotic protein Bcl-w and Bcl-2 increased significantly in the hippocampus of rats following SE (P<0.01, n=5), and EA pretreatment at Baihui and Dazhui acupoints didn't affect the expression of them (P≧0.05,n=5).5) EA stimulation at two non-acupoints (located in close vicinity to the Baihui and Dazhui acupoints) had no effect on the cognitive impairment induce by SE, and didn't alter the expression of Bcl-2 family proteins, either (P≧0.05, n=5). To sum up, the primary data in this study have provided evidence for the first time that EA pretreatment,especially at the Dazhui and Baihui acupoints, has neuron protection effects during epilepsy, and improved the cognitive impairment induced by seizures. Its mechanisms include down regulating the expression of pro-apoptotic Blc-2 family protein Bim, Bid and Bax. The over expression of anti-apoptotic protein Bcl-2 and Bcl-w is a self-protection pathway of neurons following seizures. The present study affords a novel insight into the protection of the brain from epilepsy injury,and offers a helpful method to prevent the cognitive impairment of epilepsy patients. |
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