Objective: To investigate the roles of cation-chloride cotransporters-Na, K, 2Cl(-) cotransporter-1 (NKCC1) and K(+)-Cl(-) cotransporter-2 (KCC(2)) in the epileptogenesis of cortical dysplasia.
Methods: Six pregnant SD rats were given intraperitoneal injection of 1-3-bis-chloroethyl-nitrosourea (BCNU) on the embryonic day 17 (E17) and gave birth of 56 pups (experimental group) on the day P21. Five pregnant SD rats were given intraperitoneal injection of normal saline and gave birth of 48 pups (control group) on the day E21. Sixty days after birth the brains of 24 male pups in the experimental group and 22 male pups in the control group selected randomly were taken out to isolate the hippocampus. Cresyl-violet staining was applied to observe the histological alterations in the hippocampus. RT-PCR was used to detect the mRNA expression of NKCC1 and KCC2.
Results: Cresyl-violet staining revealed heterotopic cell clusters within the hippocampus. RT-PCR showed that the ratio of NKCC1 to beta-actin of the experimental group was 0.70 +/- 0.13, significantly higher than that of the control group (0.48 +/- 0.09, P < 0.01); while the ratio of KCC2 to beta-actin of the experimental group was 0.54 +/- 0.10, significantly lower than that of the control group (0.80 +/- 0.15, P < 0.01).
Conclusion: The upregulation of NKCC1 mRNA and the concomitant downregulation of KCC2 mRNA may be deeply related to the mechanism of epileptogenicity in cortical dysplasias.