Objective: To investigate the effect of focal cerebral ischemic preconditioning on the expression of nuclear factor kappa B (NF-κB) and its target gene inducible nitric oxide synthase (iNOS) and to explore its role in ischemic tolerance in rats.
Methods: A total of 32 SD rats were divided into 4 groups. The control group received sham surgery (SS) twice only. The IPC + SS group received 10 minutes of ischemic preconditioning (IPC) followed by SS 3 days later. And the other two groups received 2 hours of middle cerebral artery occlusion (MCAO) followed by 22 hours of reperfusion with or without IPC 3 days before. The ultrastructure, NF-κB activation and iNOS mRNA transcription were evaluated in each group by electron microscope, immunohistochemistry staining and reverse transcriptase polymerase chain reaction (RT-PCR) respectively.
Results: (1) In contrast with the SS + SS group, there was a lower NF-κB immunoreactivity (57.3 ± 6.3) and iNOS mRNA level (29.1% ± 3.1%) in the IPC + SS group while no ultrastructural abnormality was identified. (2) The expression of NF-κB/iNOS was down-regulated in the IPC + MCAO group (81.2% ± 7.3%/89.0% ± 5.3%) than in the SS + MCAO group (98.9% ± 9.4%/132.8% ± 7.9%, P < 0.01) with minor ultrastructure abnormality.
Conclusion: A down-regulated expression of NF-κB/iNOS is a key event in the molecular mechanism of cerebral ischemic tolerance. And the NF-κB/iNOS pathway might play a dual role in endogenous neuroprotection induced by focal IPC.