Activation of nucleotide-binding oligomerization domain-containing protein 1 by diaminopimelic acid contributes to cerebral ischemia-induced cognitive impairment

Cerebral ischemia-reperfusion (I/R)-induced brain tissue injury is a major obstacle for acute stroke management. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is reported to play a critical role in the regulation of myocardial or hepatic I/R injury. However, its role in cerebral I/R remains elusive. The mouse model of middle cerebral artery occlusion (MCAO) was applied in the study. The cerebral I/R mice were received either PBS or diaminopimelic acid (DAP)-pretreatment. All sham, MCAO, and MCAO + DAP mice were subject to the neurological behavior tests. The proinflammatory cytokines and autophagy-related proteins were determined by ELISA, RT-qPCR, and Western blot analysis, respectively. We found that NOD1 was substantially upregulated in the hippocampus of MCAO mice. DAP treatment significantly enhanced proinflammatory cytokine production and autophagy-related protein expression, leading to enlarged cerebral infarction size and poor neurological performance in MCAO + DAP mice compared to MCAO mice. We concluded that activation of NOD1 promotes cerebral I/R injury suggesting that NOD1 may serve as a promising target for alleviating the adverse effects of cerebral I/R.