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

Li Yan; Li Yun-Lin; Liu Yong-Ling; Zhang Wei-Wei; Piao Yue-Shan

doi:10.1016/j.eplepsyres.2023.107180

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

Epilepsy Res. 2023 Aug:194:107180. doi: 10.1016/j.eplepsyres.2023.107180. Epub 2023 Jun 15.

Authors

Li Yan¹, Li Yun-Lin², Liu Yong-Ling¹, Zhang Wei-Wei³, Piao Yue-Shan⁴

Affiliations

¹ Department of Pathology, Haidian Hospital, Haidian District of Peking University Third Hospital, Beijing, China.
² Department of Neurosurgery, Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
³ Department of Pathology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.
⁴ Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Clinical Research Center for Epilepsy, Capital Medical University, Beijing 100053, China; National Center for Neurological Disorders, Beijing 100053, China. Electronic address: yueshanpiao@126.com.

PMID: 37352729
DOI: 10.1016/j.eplepsyres.2023.107180

Abstract

Background: The 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.

Methods: The 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.

Results: The 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.

Conclusions: The 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.

Keywords: Focal cortical dysplasia type II; GABAergic neurons; NKCC1/KCC2.

MeSH terms

Epilepsy* / etiology
Focal Cortical Dysplasia*
GABAergic Neurons / metabolism
Humans
Symporters* / metabolism

Substances

Symporters

Supplementary concepts

Focal cortical dysplasia of Taylor