Remote ischemic postconditioning protects ischemic brain from injury in rats with focal cerebral ischemia/reperfusion associated with suppression of TLR4 and NF-кB expression

Abstract

Remote ischemic postconditioning (RIPC) has been proven to be a promising protective method for brain damage caused by transient focal ischemia/reperfusion (I/R) injury. However, the underlying mechanism of RIPC remains elusive. To address whether RIPC protects against brain damage by regulating TLR4 and the NF-κB pathway, focal I/R rat (SD) model induced by 1 h transient middle cerebral artery occlusion was used in this study. RIPC treatment was generated by three cycles of 10 min occlusion and 10 min release of the bilateral hind femoral arteries. The Garcia JH score was used to evaluate neurobehavioral function and triphenyltetrazolium chloride staining was used to estimate the infarct size of the brain. The expression levels of TLR4 and NF-κB were determined by quantitative PCR and immunohistochemistry. The results showed that RIPC treatment significantly improved neurological deficits and decreased infarct volume. Furthermore, it also inhibited the overexpression of TLR4 and NF-κB induced by middle cerebral artery occlusion reperfusion. Thus, we suggested that RIPC might protect ischemic brain against I/R injury in rats by suppressing the TLR4/NF-кB pathway.

Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

“…A recent study revealed that remote IPC might protect against cerebral I/RI by suppressing the TLR4/NF-кB signaling pathway [15]. Previous studies have demonstrated that ALA could significantly suppress inflammation via reduce TLR4 and NF-κB activation [16,17].…”

Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke

“…Remote ischemic post-conditioning (RIPC) constitutes an alternative noninvasive neuroprotective approach which has been purported to suppress AQP4 expression, and thus limit edema formation in models of focal cerebral ischemia [ 62 , 81 , 82 ]. RIPC proposes that recurrent, rapid exposures to brief ischemia in the early phase of reperfusion can induce tolerance to a more severe long-term ischemic insult, in the same or even a remote organ.…”

“…RIPC proposes that recurrent, rapid exposures to brief ischemia in the early phase of reperfusion can induce tolerance to a more severe long-term ischemic insult, in the same or even a remote organ. Employing hindlimb clamping to occlude blood flow post-MCAO resulted in a decreased number of AQP4-positive cells and reduced AQP4 mRNA levels at 24 h in comparison to MCAO controls [ 81 , 82 ]. Additionally, RIPC suppressed activation of the transcription factor nuclear factor-κB (NF-κB), a known activator of AQP4, suggesting that the therapy may modulate AQP4 expression by downregulating the NF-κB pathway [ 82 ].…”

“…Employing hindlimb clamping to occlude blood flow post-MCAO resulted in a decreased number of AQP4-positive cells and reduced AQP4 mRNA levels at 24 h in comparison to MCAO controls [ 81 , 82 ]. Additionally, RIPC suppressed activation of the transcription factor nuclear factor-κB (NF-κB), a known activator of AQP4, suggesting that the therapy may modulate AQP4 expression by downregulating the NF-κB pathway [ 82 ]. RIPC also limited parenchyma water content, attenuated the swelling of astrocytic foot process, decreased infarct volumes, and precluded BBB disruption [ 62 , 82 ].…”

“…Additionally, RIPC suppressed activation of the transcription factor nuclear factor-κB (NF-κB), a known activator of AQP4, suggesting that the therapy may modulate AQP4 expression by downregulating the NF-κB pathway [ 82 ]. RIPC also limited parenchyma water content, attenuated the swelling of astrocytic foot process, decreased infarct volumes, and precluded BBB disruption [ 62 , 82 ]. Although RIPC has shown promise in experimental models of cerebral ischemia, it failed to have any influence on AQP4 expression levels and did not confer any significant beneficial effects in an ICH rat model at either 24 or 72 h post-surgery [ 83 ].…”