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The TLR9 Antagonist iCpG-ODN at Different Dosages Inhibits Cerebral Ischemia/Reperfusion Injury in Mice

[ Vol. 16 , Issue. 5 ]

Author(s):

Ying Zhou, Jingrui Pan, Qingxia Peng, Zhaofei Dong, Lingna Deng and Yidong Wang   Pages 624 - 633 ( 10 )

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.

Keywords:

Brain injury, cerebral ischemia/reperfusion, inflammatory responses, inhibitory oligodeoxynucleotide, toll-like receptor 9, pathology.

Affiliation:

Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yan Jiang Xi Road, Guangzhou 510120, Guangdong Province

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