Brain Microdialysis / Depth Electrodes In The Rehabilitation Of Cerebral Ischemia

Ischemic stroke is a leading cause of death and disability worldwide, and it is related to extreme release of glutamate resulting from a transient or permanent reduction in cerebral blood flow,which leading to excitotoxicity. The current researches show that a lot of neuronal diseases including cerebral ischemia,epilepsy and Parkinson's Disease are related to the imbalance of neurotransmitters.The neuroelectrical signals show different patterns or characters of activity duing to the destruction to physilogical basis results from neurotransmission disorder.So the main task of this research is to investigate the changes and relationship between neuroelectrical and neurochemical signals under different physilogical and pathological conditions by combinating the brain microdialysis and deep brain electrode techniques.We first discuss several factors which influence the performance of probe such as construct,temperature,materials and dialysis time by using a serials of in vivo/vitro experiments.With the opmized probe,the usual methods for calibration and validation are investigated and discussed.We also establish a system platform for probe design,manufacture and validation.The self-made probe meets the requirement for in vivo experiment after comparition with international commercial products.Combining the high performance liquid chromatography technique,we set up a highly sensitive method for simulatneous detect the amino acids neurotransmitters and monoamine neurotransmitters and their metabolites. The method for sampling and storing monoanime was simplified with the self-made sampler.We also establish an experimental platform for deep brain stimulation(DBS)and deep brain record(DBR).Combinated with spectral evaluation method based on autoregressive model parameters, complexity analysis methods based on symbofic dynamics and approximate entropy,the signals from the injuried brain regions can recorded and analyzied.Using above neurochemical and neuroelectrical techniques,we acquire the changes of neurtransmitter and electrical signals from striatum and hippocampus in the model rat of middle cerebral artery occlusion(MCAo). The results show that during the ischemic periods the concentration of a few neurotransmitters and percentage of Delta components significantly increased the amplitude of local field potential and complexity of signals decreases.Based on above models and methods,we study the dynamic profile of neurotransmitter intervened by drugs on MCAo rats.The results show that puerarin and gastradin effectively inhibit the excitotoxity induced by cerebral ischemia.The peak value of glutamate in drugs group lower 24～48%than that of control group,the ratoi of glutamate and GABA is abouthe 44～4%. It demostrates the protective effects of both traditional chinese medicine on acute brain injuries in molecular way and the huge potentials of these techniques in research and development in medicine.The changes of amino acids neurotransmitters of stroke model animal were studied in this work when they recept the physical tremedies,such as functional electrical stimulation(FES)and exercises.Both FES and exercises upregulate the level of Glu in brain and intervene taurine and GABA.The similar results have never been reported.It shows that the physical rehabilitation is related to the plasticity of brain and that it plays a key role in chronic post-stroke rehabilitation.On the base of above works,we combine the brain microdialysis and DBR together to create a microdialysis/electrode combined apparatus to realize the bi-direction function of microdialysis and deep brain dectrode in the same site.We use it in there animal experiments for primary exploration for its application(1)microdialysis and deep brain recordings-to simultaneously detect the neurochemical and neurodectrical signal from the same region during cerebral ischemia period;(2)retro-microdialysis and deep brain recordings-to measure the basic levd of glutamate and local intervention of extrinsic glutamate in hippocampus;(3)microdialysis and deep brain stimulation-to investigate the changes of amino acids and monoamine neurotransmitters invoked by stimulation in VTA and provide a new tools for researches in mechanism underlying rewards and DBS.All above results show that the brain microdialysis,deep brain electrodes and combinated apparutus with synchronous,quantitative and neurochemical-neurodectrical multi-parameters analysis methods can play a key role in investiagting the pathological mechanism underlying neural system diseases,evaluation the effects of drugs.