Neuroimmunomodulation With Nerve Injury-related Signals

Anatomical structures and signal transduction of Neuroendocrin-immune network are the basic theory of Neuroendocrine-immune regulatory network, the afferent pathways and the functional signals of the afferent signal transduction of this network have been considered the most controversial field,our research work of afferent pathways and signal transduction would contribute to establish the well-defined mechanisms of interaction between the central neural system and the immune system.There are two controversial theories of afferent pathways and signal transduction,"the humoral afferent pathway"and "the neural afferent pathway".The former theory sustained, cytokines were expressed and secreted by activated immunocytes, they can get through the BBB(Blood-Brain Barrier)to initiate the activation of the brain regions related to neuroimmune regulation function while they play a role in regulation in peripheral immune system;the later theory corroborated,cytokines were expressed and secreted by activated immunocytes can act directly on neural sensor in the perpherial tissue,then initiate the functional activation of relative brain regions of neuroimmune regulation through neural afferent pathway. Some experimental evidence of our lab study supported functional signals of immune system could initiate the activation of the neurons of relative brain regions.In order to identify the cell source of functional signals in the peripheral immune system,our study used different immunized methods of Balb/c and Balb/c-nu mice to induce different immunized status and applied immunohistochemistry technique to observe the differential expression of functional IL-1 of brain regions LH,AA; for the purpose of distinguishing injury signals from regulatory signals,our study utilized middle artery cerebral occlusion model to cause focal ischemia and reperfusion of rat brain and employed injection of human IgG at rats' root to stimulate peripheral immune response,then applied SELDI-TOF-MS technique to analyse expressed proteins of rat serum of injured and immunized model.Innate immune cells such as dendritic cells could recognize and process the invading pathogenic microorganisms, then present the antigen peptide to T help cells to launch the specific immune response. Due to lack of T cells, dendritic cells of Balb/c-nu cannot present the antigen signal to T cells. If the neuroimmune regulatory activated signals were all expressed by dendritic cells,then the function activation of central brain regions related to neuroimmune regulatoion couldn't been influenced of peripherally immunized Balb/c-nu rats compared to Balb/c mice;if the neuroimmune regulatory activated signals were all expressed by Th cells,then the function activation of central neuro-immune brain regions would disappear of peripherally immunized Balb/c-nu mice;if the the neuro-immune regulatory activated signals were expressed by dendritic cells and Th cells jointly,then the function activation of central neuro-immune brain regions can be changed partially compared to Balb/c mice.Two different models of immune regulation and immune injury play a part in immune respose.The process of activated immune cells and molecules of immune injury mechanism seems similar among different diseases,but immune regulation is complicate and continuously active during whole immune response.Pathological mechanism of focal cerebral ischemia and reperfusion injury model was tightly related to injured-injury repair process but not immune response and immune regulation;immunized rats models included immune injury and immune regulation,we detected the expressed proteins in serum of different models to ascertain the immune regulatory relative signals,especially early signals of immune regulation.Our experimental results demonstrated that:1.We injected human IgG at root of Balb/c and Balb/c-nu mice to induce different immunized status,applied immunohistochemistry technique to observe the expression level of IL-1βof brian regions related to neuroimmue regulation.The results proved expression level of IL-1 of immunized Balb/c and Balb/c-nu mice were significantly higher than the control group;the result of different immunized group of Balb/c mice showed that brain regions of immunized 2 days expression level began to increase,immunized 4 days reached the peak,immunized 6 days began to decrease,and immunized 8 days got the baseline of physiological level,the expression trend of the Balb/c-nu mice was similar to the Balb/c mice.These results suggested that the function of neuroimmune regulation of Balb/c-nu have already been activated,and the relative model of function is similar to Balb/c mice.2.The result of differential expression of Il-1βof brain regions between Balb/c and Balb/c-nu mice showed that,the expression level of Il-1βof brain regions of Balb/c-nu mice are all lower than Balb/c mice at different time points,but the difference are not significant after statistic analysis.Above all,our study demonstrated the initial functional signals of neuroimmune regulation were expressed by dendritic cells and T help cells conjointly,then the information of peripheral immune system were signaled to the central neural system through neural transduction pathway,furthermore, expression of IL-1 of functional brain regions were down-regulated under the status of lacking T cells of Balb/c-nu mice3.We established the MCAO model and rats root injection of human IgG model and applied SELDI-TOF-MS technique to observe the change of serum proteins of Injured groups at 12hr,24hr,48hr,72hr,96hr,and 144hr six time points and immunized groups at 12hr,24hr and 48hr three time points.The results indicated that serum of all injured groups had 425 differential peaks totally(M/Z range:1000-50000u), there were 64,94,82,68,68,49 differential peaks at 12hr,24hr,48hr,72hr,96hr,144hr time points respectively; all immunized groups had 204 differential peaks(M/Z range:1000-50000u),there were 57,98,49 differential peaks at 12hr,24hr,48hr time points respectively.The experimental results concluded that immunized and injured groups were significantly different from the control,and the difference among the control group and immunized,injured groups were most noticeable at 24hr time points.4.Utilizing SELDI-TOF-MS technique to exam the difference between injured and immunized group at 24hr time point revealed that there were 55 differential peaks including 22 opposite expressed peaks,15 simultaneously increased peaks,18 simultaneously decreased peaks.22 opposite expressed peaks included 15 injured 24hr group increased expression peaks while immunized 24hr group decreased expression;5 immunized 24hr group increased expression peaks while injured 24hr group decreased expression;2 injured 24hr group nearly didn't change but immunized 24hr group increased or decreased expression.From the results of our study,we concluded expression of injured signals of injured and immunized groups coincided with the basic rule of functional regulation network,they implied that combination of simple signals could transduce complicate regulatory physiological information.Our next task will distinguish the regulatory from the injured signals and identify these specific functional signals.