Title:The TLR9 Antagonist iCpG-ODN at Different Dosages Inhibits Cerebral Ischemia/Reperfusion Injury in Mice
Volume: 16
Issue: 5
Author(s): Ying Zhou, Jingrui Pan, Qingxia Peng, Zhaofei Dong, Lingna Deng and Yidong Wang*
Affiliation:
- Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yan Jiang Xi Road, Guangzhou 510120, Guangdong Province,China
Keywords:
Brain injury, cerebral ischemia/reperfusion, inflammatory responses, inhibitory oligodeoxynucleotide, toll-like receptor
9, pathology.
Abstract: Background: Inflammatory responses are important mechanisms that are involved in cerebral
ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate
immune system, takes part in the inflammatory responses following cerebral I/R remains unclear.
Method: This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide
(iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral
artery occlusion. Neurological function, infarct size, splenocytes and the expression of TLR9 and the
downstream products of the TLR9 pathways were determined after cerebral I/R for up to 72 hours.
Results: The Clark's focal symptom scoring showed iCpG-ODN improved neurological deficits following
focal cerebral I/R. The iCpG-ODN administration significantly decreased the infarct size in a
dose-dependent manner. RT-PCR showed that iCpG-ODN attenuated the I/R-induced RNA expression
of TLR9. Immunoblot showed that iCpG-ODN prevented I/R-induced increases in NFκB and IRF7
levels and that it further downregulated the levels of IL-1β, TNF-α, and INF-β in the brain. iCpG-ODN
did not alter the levels of TNF-α or INF-β in the peripheral blood or affect stroke-induced changes in
the number of splenocytes.
Conclusion: These findings suggest that iCpG-ODN induced protection against cerebral I/R via inhibiting
inflammatory responses in a dose-dependent manner and may be useful in therapy for stroke patients.
