Abstract
In the central nervous system, interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α have a regulatory role in pathophysiological processes of epilepsy. In addition, γ‐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‐1β, IL‐6 and TNF‐α, and expression of GAT‐1 and GAT‐3 in the parietal cortex, hippocampus and amygdala of rats with nonconvulsive 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‐1β, IL‐6 and TNF‐α. 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.
Highlights
Cerebral ischaemia is considered as one of the great risk factors for progress of seizures and the incidence of seizures induced by post‐ischaemia presently tends to increase.[1]
In order to determine the basic role of central GABAergic transmission in the process of epileptic activity following cerebral ischaemia,[11,12] in the current study, we performed the middle cerebral artery occlusion (MCAO) in rats to induce post‐ ischaemic nonconvulsive seizure (NCS) and further determined the protein levels of GAT‐1 and GAT‐3 in the parietal cortex, hippocam‐ pus and amygdala
We showed that inhibition of miR‐155 decreases ischaemia‐activated proinflammatory cytokines (PICs), and this attenuates upregulation of GABA transporters and thereby stabilizes GABA in the parietal cortex, hippocampus and amygdala
Summary
Cerebral ischaemia is considered as one of the great risk factors for progress of seizures and the incidence of seizures induced by post‐ischaemia presently tends to increase.[1]. Among various miRNAs, microRNA‐155 (miR‐155) plays a role in various physiological and pathological processes.[22,23,24,25] MicroRNA‐155 is involved in chronic immune response by amplifying the prolifera‐ tive response of T cells via the downregulation of lymphocyte‐asso‐ ciated antigens.[26] In autoimmune disorders, a higher expression of miR‐155 is observed in patients' tissues and synovial fibroblasts.[24] In multiple sclerosis, upregulation of miR‐155 has been observed in peripheral nerve and CNS‐resident myeloid cells, blood monocytes in the circulation and stimulated microglia.[27] a prior study has suggested that miR‐155 is involved in inflammation and upregulation of miR‐155 results in chronic inflammation in human beings.[25] It remains unknown for the role of miR‐155 in engagement of post‐ischaemic seizures. We hypothesized that inhibition of miRNA‐155 improves NCS following MCAO through PIC‐GABA mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
