Non-invasive remote limb ischemic postconditioning protects rats against focal cerebral ischemia by upregulating STAT3 and reducing apoptosis

Abstract

The signal transducer and activator of transcription 3 (STAT3) signaling pathway has been implicated in cell apoptosis and inflammatory processes. Ischemic preconditioning (IPC) and ischemic postconditioning (IPTC) inhibit both of these processes. In the present study, we investigated the role of phosphorylated STAT3 (p-STAT3)-mediated apoptosis and inflammation following non-invasive remote limb IPTC (NRIPoC) using a classic rat model of focal cerebral ischemia. Forty-five adult male Sprague-Dawley rats were divided randomly into 3 groups (n=15 per group): the sham-operated, ischemia/reperfusion (I/R) and NRIPoC groups. NRIPoC was implemented at the beginning of reperfusion. At 24 h after cerebral reperfusion, we evaluated the neurological deficit score (NDS), assessed the cerebral infarct size and tissue morphology, and evaluated neuronal apoptosis. The protein expression levels of Bcl-2, Bax, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α) and p-STAT3 in the penumbra region were assessed by western blot analysis. The cerebral infarct volume, the number of apoptotic cells and the protein expression levels of Bcl-2, Bax, NF-κB and TNF-α were all found to be increased in the I/R group compared with the sham-operated group. However, these levels were decreased in the NRIPoC group compared with the I/R group. The number of apoptotic cells in the penumbra in the I/R group was increased compared with that in the NRIPoC and sham-operated groups. The protein expression of p-STAT3 was increased in the NRIPoC group compared with the sham-operated and I/R groups. These results indicate that the protective effects of NRIPoC against cerebral I/R injury may be related to the attenuation of neuronal apoptosis and inflammation through the activation of STAT3.

Inhibition of miR‐337‐3p involved in the protection of CoCl2‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

“…Besides, the JAK2/STAT3 signaling pathway can also be activated to reduce the apoptosis of neurons, thereby, improving the brain dysfunction . Furthermore, the improved cerebral ischemia/reperfusion injury presented by Cheng et al may be associated with the reduced neuronal apoptosis via activating STAT3 . Mechanically, the JAK2/STAT3 pathway is activated by the cytokines or the phosphorylation of JAK2 and STAT3 promoted by the activation of receptors on the membrane by hormones, and the activated JAK2/STAT3 further activate the target genes ( Bcl‐2 and Bcl‐XL ) inside the nuclei to antagonize the cell apoptosis …”

Electroacupuncture at GV20 and ST36 Exerts Neuroprotective Effects via the EPO‐Mediated JAK2/STAT3 Pathway in Cerebral Ischemic Rats

“…JAK2, in turn, phosphorylates STAT3, and STAT3 subsequently dimerizes and accumulates in the nucleus where it binds to target genes with specific sites to elicit mitogenic signals. The physiological and pathological processes of inflammation, cell survival, proliferation, and cell angiogenesis were regulated by JAK2/STAT3 signaling after CIRI in animal models [ 37 , 38 ]. Several downstream target gene products, such as Bcl-2, Bcl-XL, and the Caspase and Bax protein families, were activated after JAK2/STAT3 binding to specific gene promoters [ 39 , 40 ].…”

The role of p38MAPK signal pathway in the neuroprotective mechanism of limb postconditioning against rat cerebral ischemia/reperfusion injury

“…Based on recent studies on the experiments in the brain, remote ischemic postconditioning probably trigger endogenous neuroprotective mechanisms by acting on different proteins involved in ionic transport, G protein-coupled receptors and kinase signaling pathways, reducing apoptosis and free radical products, eliciting ischemic tolerance, and ultimately attenuate neuronal damage [12,13].…”