The Expression Of D-serine And N-methyl-D-aspartate Receptor 1 In The Central Nervous System And Their Roles In Refractory Epilepsy

Objective:To discuss the roles of D-serine and NMDA receptors in the pathogenesis of refractory epilepsy.Methods:D-serine differential expression is detected in temporal lobe brain tissue of 20 patients with refractory epilepsy and 6 cases of traumatic brain injury by Immunohistochemistry, while NMDAR1 is detected by western blot.Results:1.Comparison of clinical characteristics:refractory epilepsy group are 20 temporal lobe brain tissues of patients with refractory epilepsy, while 11 cases were male and 9 were females; they aged 17-58 years and mean 27.7±11.13 (x±S)years old; The duration of disease were 2-29 years, and mean 9.45±7.65 (x±S) years; 14 patients (70%) had a history of seizure for more than 5 years,7 patients (35%) had a more than 10 years history. Seizure types mainly represent complex partial seizure, eneralized tonic-clonic seizure and simple partial seizure. Neuropathology (HE staining) are mainly neuronal degeneration, gliosis and neuron loss. In 20 patients with refractory epilepsy of head MRI,4 cases were no obvious abnormality, and the other 16 cases can be seen the abnormal signal corresponding abnormal discharge; abnormal signals mainly were reduced hippocampal volume, the high Signal of T2 and FLAIR sequences in temporal lobe, disorded the internal structure of the hippocampus, ill-defined grey matter, increased lateral ventricle temporal horn and so on. Long video EEG monitoring in Case group were abnormal discharge:3 patients with mild abnormalities and 17 patients with severe abnormalities. Control group were 6 cases temporal cortex brain tissue of brain trauma, while 4 cases were males and 2 cases were females. They aged 19-55 years and mean 36.83±16.31 years old. There was no significant difference in age, gender and the anatomical location of brain tissue between refractory epilepsy group and control group(P>0.05).2. Immunofluorescence staining:D-serine of IOD was 13.37±1.88 in temporal lobe brain tissue of refractory epilepsy group, while was 9.27±0.62 in control group. There was a significant difference between refractory epilepsy group and control group(P<0.05).3. Double immunofluorescence staining:D-serine were distributed in both neurons and glial cells in refractory epilepsy group and control group.4. Western blot:NR1 has a protein band in 105kDa. The relative gray values of patient group (0.4175±0.2321) was significantly higher than the relative gray values of control group(0.2402±0.1558) (P<0.05).Conclusion:D-serine and NMDAR1 expression increased in patients with refractory epilepsy; D-Serine which were released by astrocytes and Neurons possibly involved in the pathogenesis of epilepsy and recurrent through over-activation of NMDA receptors and excitotoxicity.