Role of microRNA-155 in modifying neuroinflammation and γ-aminobutyric acid transporters in specific central regions after post-ischaemic seizures.

In the central nervous system, interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha have a regulatory role in pathophysiological processes of epilepsy. In addition, gamma-aminobutyric acid (GABA) transporter type 1 and type 3 (GAT-1 and GAT-3) modulate the levels of extracellular GABA in involvement in the neuroinflammation on epileptogenesis. Thus, in the current report we examined the effects of inhibiting microRNA-155 (miR-155) on the levels of IL-1 beta, IL-6 and TNF-alpha, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala of rats with non-convulsive seizure (NCS) following cerebral ischaemia. Real time RT-PCR, ELISA and Western blot analysis were used to examine the miR-155, proinflammatory cytokines (PICs) and GAT-1/GAT-3 respectively. With induction of NCS, the levels of miR-155 were amplified in the parietal cortex, hippocampus and amygdala and this was accompanied with increases of IL-1 beta, IL-6 and TNF-alpha. In those central areas, expression of GAT-1 and GAT-3 was upregulated; and GABA was reduced in rats following NCS. Intracerebroventricular infusion of miR-155 inhibitor attenuated the elevation of PICs, amplification of GAT-1 and GAT-3 and impairment of GABA. Furthermore, inhibition of miR-155 decreased the number of NCS events following cerebral ischaemia. Inhibition of miR-155 further improved post-ischaemia-evoked NCS by altering neuroinflammation-GABA signal pathways in the parietal cortex, hippocampus and amygdala. Results suggest the role of miR-155 in regulating post-ischaemic seizures via PICs-GABA mechanisms.