The Change Of NOS In The Corpus Striatum Of ICH Rabbit Model And The Neuroprotection Roles Of NOS Inhibitor L-NNA And Xuesaitong In ICH Model

The animal model of intracererebral hemorrhage (ICH) was established with rabbits inthis paper, and then Xuesaitong and NOS inhibitor L-NNA were respectively used to treat thesuccessful animal model. To study the relationship between the pathologic mechanism of ICHand NO, and the effect of NOS inhibitor L-NNA on NO, NOS and dopaminergic neuron inthe main diseased region, the content of NO, the activity of NOS and the expression of NOSpositive neurons in frontal lobe, Substantia Nigra, Corpus Striatum were determined in everygroup of rabbits.The method of modeling intracererebral hemorrhage (ICH) by injecting autologousblood into right side of rabbit corpus striatum with cerebral stereotaxis and microinjectiontechnique was used in this study, and then behavior test and Immunohistochemical methodwere used to detect the ICH rabbit model. The result of behavior test showed there were80%of rabbits achieving the standard of success. TH immunohistochemical staining showed thatthe TH positive neurons were seen within the nigral in normal control group, sham surgerygroup, and the unlesioned side of model group. They had the hyperchromic cytoplasm, theclear tubers, numerous positive cells and the long axons, which had no noble change in abovethree groups. While in the opposite area of the model group TH positive neuron stainingbecame lighter, cell body and tuber got blurrier, especially, the number and the axons`lengthof the TH-positive neurons decreased and got shorter dramatically than that in the unlesionedside of the model group and the other two groups. The ICH rabbit model’s reliability wasconfirmed by the performance test result.The level of NO in the serum, the content of NO, the activity of NOS and the expressionof NOS positive neurons in frontal lobe, Substantia Nigra, Corpus Striatum were determinedin every group of rabbits by the method of nitric acid reductase and metabolic chemistralmethod. Results: there was a significant increase of NO levels in the serum and every brain tissue of model group and madopar therapy group compared with control group and shamsurgery group, while there was no noble difference between L-NNA therapy group andcontrol groups. The order of TNOS activity in frontal lobe, Substantia Nigra, Corpus Striatumof all groups were: the lesioned side of model group> the lesioned side of madopar therapygroup> the unlesioned side of model group> the lesioned side of L-NNA therapygroup>normal group and sham surgery group. In addition, the order of activity of iNOS andnNOS in frontal lobe, cNOS in the Corpus Striatum, iNOS in the midbrain (including theSubstantia Nigra) was as the same as the activity of TNOS. Nevertheless, the iNOS activityin Corpus Striatum and nNOS in midbrain (including the Substantia Nigra) were low in everygroup. Besides, there was no noble difference in all groups.TH-positive neuron in Substantia Nigra and nNOS, iNOS positive neurons in frontallobe, Substantia Nigra, Corpus Striatum were observed with immunohistochemical staining.Results: there were the contrary trend between the expression of nNOS and iNOS in frontallobe, iNOS in Substantia Nigra, nNOS in Corpus Striatum and TH-positive neuron inSubstantia Nigra. Compared with the madopar therapy group, NOS positive neurons inL-NNA therapy group rabbits were close to the level of control group rabbits. Finally, therewas no nNOS positive neurons observed in Substantia Nigra, and no iNOS positive neuronsin Corpus Striatum.The results indicated that the missing and death of dopaminergic neurons in the lesionedside of model group rabbits were accompanied by increases of NO content in chief braintissue and the expression of nNOS and iNOS in frontal lobe, iNOS in Substantia Nigra, nNOSin Corpus Striatum. They suggested NO may be involved in the pathogenesis of ICH rabbitmodel, and there were different isoforms of NOS playing a major role in different brain tissue.Moreover, the protection of NOS inhibitor L-NNA in dopaminergic neurons was good. Inview of the similarity between the model and ICH patient, NO may be involved inpathogenesis of ICH, which provides a new thread of ICH Pharmaprojects.