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Neuroprotective Effect of Acupuncture on Cerebral Ischemic Injury and its


 

Acupuncture therapy is an effective method in the treatment of ischemic stroke, but its mechanism is not fully understood. Since l992 in our laboratory using several kinds of cerebral ischemic animal models, we have studied the acupuncture effect on the acute cerebra ischemia and its mechanisms. Using power spectrum analysis for EEG and record of somatesthesia evoked potentials (SEP) we studied the effect of acupuncture on the models of gerbil and rat transient cerebral ischemia/reperfusion. It was observed that during cerebral ischemia the amplitude of EEG/SEP was severely inhibited, and after reperfusion the recovery was slow in comparison with the control group, acupuncture remarkably improved the recovery of EEG/SEP after ischemia and reperfusion.
By neurological examination and CT imaging on 120 patients with acute ischemic stoke the changes of nervous functional defects and cerebral infarct areas were investigated. The data showed that the number of the patients with reduced nervous functional defects and cerebral infarct areas after treatment in acupuncture plus drug group was more than that of the drug group. Morphological observation (TTC and H&E staining) showed that after cerebral ischemia, severe ischemic neuronal damage was confined mainly to the hippocampus, striatum and cortex. Acupuncture reduced the neuronal damage.
To clarity the effect of acupuncture on extracellular excitatory amino acids (EAA) changes during cerebral ischemia the middle cerebral artery occlusion (MCAO) model and HPLC-fluorescence detection were used. It was observed that the extracellular glutamate (Glu) and aspartate (Asp) greatly increased. Electro-acupuncture (EA) resulted in significant attenuation in both glutamate and aspartate. But the inhibitory amino acids, especially taurine elevated during ischemia were increased by acupuncture to an advanced level.

The excitatory amino acid inhibitor (DM) and taurine have been proposed to have antiexcitotoxic and antihypoxia activity so the neuroprotective effect of acupuncture against cerebral ischemia might be partially related to its ability to decrease the extracellular level of excitatory amino acids and to increase that of taurine. To explore whether taurine could influence neuronal calcium overload provoked by glutamate or hypoxia, we employed Fluo-3 imaging of intracellular calcium ([Ca2+]i) in confocal laser scanning microscope to measure real-time changes of [Ca2+]i arisen from glutamate/2,4-dinitrophenol (DNP, mimic hypoxia) and taurine in cultured hippocampal neurons. We found that taurine could inhibit [Ca2+]i elevation ascribed to glutamate or DNP.

By immuno-histochemical method we also studied the c-fos protein expression in neurons of gerbil hippocampus 10 minutes after cerebral ischemia. The results indicated that acupuncture remarkably increased the induction of c-fos protein in neurons of varied regions in hippocampus following transient cerebral ischemia, especially in the CA1 sector.

By using nitric oxide (NO) sensitive electrode with electrochemical detector, we recorded the concentration of NO in the brain. Besides, the nitric oxide syntheses (NOS) mRNA level was determined by Northern blot and RT-PCR methods. It was found that the NO concentration greatly increased after cerebral ischemia and reperfusion. EA decreased the NO level. Gene expression of three isoforms of brain NOS studied by RT-PCR demonstrated that the nNOSMA markdly increased and rmOSmRNA significantly emerged during ischemia, whereas no significant change of eNOSmRNA was observed. EA inhibited correspondingly decreased the ANOS and iNOSmMA levels, but had no effect on eNOSmRNA.
Acupuncture applied during ischemia and reperfusion could evidently alleviate cerebral lesion extent, notably upregulate the expression of bFGF, NGF, BDNF and GDNF.

These results suggest that the neuro-protective effect of acupuncture against cerebral ischemia may be related to a bi-directional regulation of neurotransmitters, intracellular factors and genes.

By Cheng Jieshi

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