Alteration of GABAergic neurons and abnormality of NKCC1/KCC2 in focal cortical dysplasia (FCD) type Ⅱ lesions

Abstract

BackgroundThe current conclusions of molecular genetics still cannot satisfactorily explain the pathogenesis of focal cortical dysplasia (FCD) and the reason for drug resistance. The interneurons of GABA deserve attention. To observe the distribution and changes of GABAergic neurons and to explore the expression of cation chloride cotransporter NKCC1/KCC2 in focal cortical dysplasia (FCD) type II lesions is a highly significant job. MethodsThe expressions of GAD67(a marker of active GABAergic neuron), NKCC1 and KCC2 were detected by immunohistochemistry and immunohistochemistry double staining in 10 cases of FCD Ⅱa and 10 cases of FCD Ⅱb. The number of GAD67 positive neurons was counted, and the average absorbance (IA) of NKCC1 positive expression was measured, using Image Pro-Plus7.0 software. The data were statistically analyzed. ResultsThe density of GABAergic neuron in focal dysplastic regions was significantly lower than that in the histologically “normal” cerebral cortex, regions from the same specimen (p < 0.0001, t-test). Compared to the NKCC1 staining intensity of neurons in the control group (measuring 1000 cells each), the IA value of dysmorphic neurons was significantly increased (p < 0.05, t′-test Cochran & Cox method). Intracytoplasmic concentration of KCC2 was evident in dysmorphic neurons but not in the other mature neurons. Most of the balloon cells were negative for NKCC1, except for few balloon cells showing sparse colored particles. The expression of KCC2 was negative in all balloon cells. ConclusionsThe changes in the expression of NKCC1 and KCC2 may indicate that dysmorphic neurons were in a state similar to that of immature neurons. This state may be related to the abnormal electrophysiology of epilepsy. The difference between the number of GAD67 positive cells in the lesion site and the remote site of the same case may be an evaluation index of the effectiveness of surgery.