前庭代偿的中枢神经化学机制研究

Vestibular compensation after unilateral labyrinthectomy(UL) is one of the ideal plasticity experimental model induced by importation loss. Many studies have demonstrated that the mechanism of compensation is differentiated in the different period after UL. Our previous study have observed that expression of c-Fos protein and phosphorylated extracellular signalregulated kinase (pERK) 1/2 shows significant differcence between ipsilateral and contralaterlal MVN to the lesion side in the acute state of UL conscious rats. In the 14 days after UL group, glutamate release and expression of c-Fos protein did not change in the bilateral MVN in conscious rats. Glutamate release and expression of c-Fos protein increased in the MVN contralateral to the lesion, but did not change in the ipsilateral MVN following acute hypotension 14 days after UL in conscious rats. And after intracerebroventricular microinjection of MK-801 or CNQX, little c-Fos protein was expressed in the bilateral MVN of these rats following acute hypotension. However, the detailed role of various kinds of neurotransmitter in the different period of vestibular compensation has not been investigated systematically in conscious rats. .Therefore, in order to investigate neurochemical mechanism underlying vestibular compensation, changes of some neurotransmitter (amino acids, monoamine, bilineurine) will be measured in the MVN of conscious rats using microdialysis and high performance liquid chromatography (HPLC).

外周前庭器官破坏后前庭代偿是一个理想的失传入诱导可塑性实验模型。已经发现，外周前庭器官损伤不同时期代偿机制有所区别。申请人前期研究发现，前庭代偿急性期清醒大鼠双侧前庭内侧核区c-Fos蛋白和pERK不对称表达；前庭代偿慢性期，双侧前庭内侧核区兴奋性氨基酸谷氨酸含量和c-Fos蛋白表达均未见明显区别，而硝普钠诱发急性低血压时双侧前庭内侧核区谷氨酸含量和c-Fos蛋白表达不对称，损伤对侧明显多于损伤侧，同时谷氨酸的受体阻断剂MK-801和CNQX可阻断此效应。但是，尚无关于前庭代偿不同时期前庭神经核区各种神经递质含量变化的系统研究报道，更无在清醒状态下的相关研究。.本研究拟在清醒动物利用核团微量透析、高效液相分析等方法，系统观察破坏外周前庭器官后不同时期，前庭神经核内氨基酸类、单胺类和胆碱能神经递质含量的动态变化，探讨前庭代偿过程中前庭神经核区的神经化学机制。

外周前庭器官破坏后前庭代偿是一个理想的失传入诱导可塑性实验模型。已经发现，外周前庭器官损伤不同时期代偿机制有所区别。申请人前期研究发现，前庭代偿急性期清醒大鼠双侧前庭内侧核区c-Fos蛋白和pERK不对称表达；前庭代偿慢性期，双侧前庭内侧核区兴奋性氨基酸谷氨酸含量和c-Fos蛋白表达均未见明显区别，而硝普钠诱发急性低血压时双侧前庭内侧核区谷氨酸含量和c-Fos蛋白表达不对称，损伤对侧明显多于损伤侧，同时谷氨酸的受体阻断剂MK-801和CNQX可阻断此效应。但是，尚无关于前庭代偿不同时期前庭神经核区各种神经递质含量变化的系统研究报道，更无在清醒状态下的相关研究。本研究拟在清醒动物利用核团微量透析、高效液相分析等方法，系统观察破坏外周前庭器官后不同时期，前庭神经核内氨基酸类、单胺类和胆碱能神经递质含量的动态变化，探讨前庭代偿过程中前庭神经核区的神经化学机制。. 研究发现：（1）UL和BL急性期清醒大鼠前庭内侧核区氨基酸类、单胺类和胆碱能神经递质含量失衡。（2）UL和BL慢性期双侧前庭内侧核区神经递质含量对称。（3）前庭代偿急性期清醒大鼠前庭内侧核区c-Fos免疫阳性神经元和c-Fos蛋白不对称表达。（4）前庭代偿急性期诱发急性低血压可使MVN区Glu含量增加，MK-801和CNQX可阻断其效应。以上结果提示，前庭代偿可塑性过程中可能有氨基酸类、单胺类和胆碱能类神经递质的参与。