An increase in AMPK/e-NOS signaling and attenuation of MMP-9 may contribute to remote ischemic perconditioning associated neuroprotection in rat model of focal ischemia

Immune Modulation as a Key Mechanism for the Protective Effects of Remote Ischemic Conditioning After Stroke

“…Under low energy conditions, higher activation of AMPK signaling pathway contributes to elevated glucose uptake and utilization in neurons. We have recently shown that RIPerC-mediated neuroprotection and collateral flow enhancement in a rat model of focal ischemia is associated with an increase in pAMPK/eNOS activity ( 86 ). AMPK is considered to be a direct activator of eNOS/NO system.…”

Remote but not Distant: a Review on Experimental Models and Clinical Trials in Remote Ischemic Conditioning as Potential Therapy in Ischemic Stroke

“…Ischemic stroke and RIC also affect expression of matrix metalloproteinases (MMPs) in the brain, which may be linked to changes in tissue and/or vessel remodeling. Ischemic stroke modeled in rat by itself increases expression of MMP-2 and MMP-9 [ 42 ], while per-RIC, immediately after 1-h MCAO, significantly reduced MMP-9 but not MMP-2 expression and activity in ipsilateral ischemic hemisphere after 24 h [ 42 ].…”

“…AMPK is activated when AMP/ATP or ADP/ATP ratios in cells rise due to physiological stresses, including ischemia. In rat, AMPK protein in whole brain [ 30 ] and p-AMPK in ischemic ipsilateral hemisphere [ 42 ] were increased 24 h after MCAO alone, and increased further in pre-RIC performed 1 h before MCAO [ 30 ] or after per-RIC [ 42 ]. Inhibition of AMPK reversed the neuroprotective effects of pre-RIC, namely, the better neurological deficit scores, lower brain water content, and increase HSP70 protein expression observed after pre-RIC [ 30 ].…”

“…In a post-RIC mouse model of IS, AMPK pathway was also activated in the cerebral cortex, 12 h after RF, as witnessed by increased p-AMPK, p-ACC, and p-ULK1 and decreased p-mTOR [ 64 ]. In per-RIC performed immediately after 1-h MCAO in rat, p-AMPK was increased more than twofold after 24-h reperfusion [ 42 ].…”

“…In rat, experimental ischemic stroke alone does not change endothelial nitric oxide synthase (eNOS) expression in ischemic ipsilateral hemisphere compared to contralateral hemisphere, but per-RIC performed immediately after 1-h MCAO, resulted in eNOS increase after 24-h reperfusion in ischemic hemisphere compared to MCAO alone [ 42 ]. In another rat model using 8-min global cerebral ischemia, limb pre-RIC increased NO and NOS activity following a double peak pattern in both serum (0 h and 48 h) and CA1 hippocampal region (6 h and 48 h) [ 77 ].…”