DhHP-6 attenuates cerebral ischemia-reperfusion injury in rats through the inhibition of apoptosis

Abstract

As a novel reactive oxygen species (ROS) scavenger, deuterohemin His peptide-6 (DhHP-6) has been demonstrated to prolong the lifespan of Caenorhabditis elegans and has also exhibited protective effects in myocardial ischemia-reperfusion injury. Whether similar effects occur during cerebral ischemia-reperfusion (CIR) injury remains to be elucidated. The present study evaluated the function of DhHP-6 and its underlying mechanisms in a middle cerebral artery occlusion (MCAO) model in rats. The focal transient MCAO model was implemented using the Longa method of ischemia for 2 h followed by reperfusion for 22 h in male Wistar rats. DhHP-6 was administered at the onset of reperfusion via intraperitoneal injection. The infarct volume, brain edema, brain apoptosis and neurological function were evaluated 24 h following stroke. To further determine the role of DhHP-6 in CIR injury, the levels of ROS and malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the protein expression levels of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), cleaved caspase-3, cytochrome c, Bcl-2 and phosphorylated-Akt/Akt were measured in ischemic cortex tissues. The results demonstrated that DhHP-6 significantly improved infarct volume, brain edema and neurological deficits, and reduced the percentage of TUNEL-positive cells. The levels of ROS and MDA were decreased, whereas no significant changes in the activities of SOD, CAT and GSH-Px were observed. The levels of Bax, cleaved caspase-3, and cytochrome c were downregulated, whereas the levels of Bcl-2 and p-Akt/Akt were upregulated. The results of the present study indicated that DhHP-6 may offer therapeutic potential for cerebral ischemia. The neuroprotective effects of DhHP-6 maybe mediated by its anti-oxidative properties, anti-apoptotic activities, or activation of the phosphoinositide 3-kinase/Akt survival pathway.

Cannabidiol alleviates hemorrhagic shock‐induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway

“…Neuro‐apoptosis is the key process associated with the pathogenesis of brain injury [30‐32]. The autophagy inducer rapamycin prevented ischemia reperfusion‐induced brain injury by regulating apoptosis by upregulating autophagy in the rat penumbra [33].…”

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

“…283,284 It is reported that inhibition of NF-κB pathway activation is involved in breaking cellular redox homeostasis and triggers ROS production and accumulation through the JNK-mitogen-activated protein kinase (MAPK) axis. 285,286 Due to high specificity and the power to cross the BBB, exosome-and nanovesicle-mediated delivery [287][288][289] of peptides, [290][291][292][293] small molecules, miRNA, [294][295][296] and other drugs in Fig. 3 Steps of focal cerebral ischemia development…”

The Effects of Electroacupuncture in a Rat Model of Cerebral Ischemia-Reperfusion Injury Following Middle Cerebral Artery Occlusion Involves MicroRNA-223 and the PTEN Signaling Pathway

“…Neuronal apoptosis occurs during cerebral ischemia and reperfusion injury, as well as glial cells and vascular endothelial cells. Recent studies have shown that the pathways that regulate apoptosis mainly include the mitochondrial, the death receptor, and the endoplasmic reticulum pathways [35,36]. In this study, in the rat model of CIRI induced by MCAO, EA had a protective role through the miR-223/PTEN pathway.…”

“…CIRI results in necrosis or apoptosis of nerve cells, which plays a crucial role in neurological deficits caused by cerebral infarction [35]. Neuronal apoptosis occurs during cerebral ischemia and reperfusion injury, as well as glial cells and vascular endothelial cells.…”