Effects of Acute Potassium Chloride Administration on Ventricular Dysrhythmias after Myocardial Infarction in a Rat Model of Ischemia/Reperfusion.

Background: Acute myocardial infarction is an important cause of morbidity. This study aimed to investigate the effects of the administration of potassium chloride (KCl) on reperfusion-induced injuries in a rat model of myocardial ischemia/reperfusion. Methods: Thirty-six male Wistar rats, weighing 200 to 250 g, were randomly assigned to 3 experimental groups: control, K1 (10 µg/kg of KCl), and K2 (20 µg/kg of KCl). Twenty minutes before ischemia, a single dose of 10 and 20 µg/kg of KCl was intraperitoneally administered in the K1 and K2 groups, respectively. The coronary artery was occluded for 30 minutes (ischemia); thereafter, it was opened for 60 minutes (reperfusion) to measure hemodynamic parameters and ventricular arrhythmias. Blood sampling was performed after the reperfusion period to determine the serum levels of lactate dehydrogenase, troponin I, creatine kinase (CK)-MB, malondialdehyde, and pro-oxidant-antioxidant balance. Results: Serological parameters significantly decreased in the potassium groups compared with the control group. In particular, the decline was more pronounced for the serum levels of lactate dehydrogenase (1180.25±69.48 vs 1556.67±77.02 U/L; P=0.011), troponin I (21.98±0.61 vs 28.76±1.65 ng/mL; P=0.020), and pro-oxidant-antioxidant balance (15.51±0.72 vs 20.63±1.42 HK; P=0.041) in the K2 group compared with the K1 group. Moreover, the administration of 20 µg/kg of KCl significantly decreased the incidence of ventricular tachycardias and fibrillations compared with the control group (P=0.002). Additionally, no considerable differences were observed between the control group and the groups with 10 µg/kg and 20 µg/kg of KCl regarding the number of ventricular ectopic beats. Conclusion: The administration of KCl before ischemia could reduce ventricular arrhythmias and reperfusion-induced injuries by reducing oxidative stress.

Adipose-derived mesenchymal stem cells reduced transient cerebral ischemia injury by modulation of inflammatory factors and AMPK signaling.

Stem cell-based treatments have been recommended as a feasible therapy for stroke victims due to their potential for angiogenesis, neurogenesis, and synaptic plasticity. The intracellular mechanisms of stem cells against cerebral hypoperfusion are not well recognized. In this study, by releasing the clips, the reperfusion period was extended to 96 h, and two hours after cerebral ischemia, animals received adipose-derived MSCs. MSCs were isolated from the inguinal fat pads of rats and injected into two-vessel occlusion (2VO) rats 1 h after ischemia induction. Ninety-six hours after 2VO induction, behavioral and molecular tests were assessed. Adipose-derived MSCs treatment improves neurological scores, passive avoidance memory, and novel object recognition tests in the 2VO model compared to 2VO rats (P < 0.001). MSCs treatment decreased TNF-α (P < 0.01) and IL-6 (P < 0.01) and apoptotic factors (Bax/Bcl-2 ratio and caspase-3 level (P < 0.01)) compared with ischemic rats. MSCs treatment of ischemic rats could enhance Klotho-α and AMPK-α compared with ischemic rats (P < 0.001). The study disclosed that adipose-derived MSCs could improve neurological damage and memory deficits by reducing neuronal death in cerebral ischemia. Data proposed that adipose-derived MSCs inhibit pro-inflammatory factors such as IL-6 and TNF-α, consequently decreasing apoptosis in the hippocampus of CCAO rats. Besides, the Klotho-α and AMPK-α measurements found that MSCs might induce intracellular neuroprotective pathways via activation of Klotho-α/AMPK-α signaling.

Dimethyl fumarate protects the aged brain following chronic cerebral hypoperfusion-related ischemia in rats in Nrf2-dependent manner.

It has been stated that chronic cerebral hypoperfusion (CCH) markedly prompts neuronal damage and affects cognition. Dimethyl fumarate (DMF), a nuclear erythroid 2-related factor 2 (Nrf2) activator, represents a class of molecules exhibiting neuroprotection. We explored the effect of DMF on CCH using a model of permanent left common carotid occlusion. The left common carotid artery was occluded and then DMF (100mg.kg-1) was orally administrated three times per week for four consecutive weeks. Behavioral rests, PET imaging and Hematoxylin and Eosin staining, were examined and also, the hippocampal level of inflammatory, Nrf2 antioxidant, neuronal plasticity and apoptotic factors were determined using Western blot analysis and related ELISA kits. The neurological deficit scores were significantly reduced in the treatment group compared with the CCH group (P<0.001). DMF decreased the novel object recognition index (NOR) compared with the CCH group, while CCH + DMF increased the NOR compared with the CCH group (P<0.001). CCH + DMF reduces the ratio of Bax/Bcl2 and capase-3 activity in comparison to the CCH group (P<0.001). Treatment with DMF increased Nrf2, NAD(P)H dehydrogenase-1 and Heme oxygenase-1 and decreased Tumor necrosis factor α and Nuclear factor-κB density compared with the CCH group (P<0.001). A significant increase in brain-derived neurotrophic factor and c-fos was found in DMF-treated rats compared with the CCH group (P<0.001). Also, retinoic acid inhibits Nrf2 activation via DMF and increases inflammatory factors in hypoperfused rats' hippocampus compared with the CCH group (P<0.001). Long-term DMF treatment induces the Nrf2 pathway and has beneficial effects on memory and motility in CCH.

Tannic acid protects aged brain against cerebral hypoperfusion via modulation of Nrf2 and inflammatory pathways.

Current study purposed to investigate the neuroprotective effects of Tannic Acid (TA) on mild chronic cerebral hypoperfusion model in rats. Male Wistar rats were subjected to permanent Unilateral Common Carotid Artery Occlusion (UCCAO), followed by TA treatment (0.05% w/v) in drinking water for one month. Nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO-1), heme oxygenase-1 (HO-1), factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, blood triglyceride, blood glucose, and liver enzymes' activity were detected after the experimental period. Also, behavioral tests, hematoxylin and eosin (H&E) staining, and PET scan were performed after treatment. Post-treatment of TA improved locomotion and memory function (P < 0.001), and reduced neural cell death (P < 0.001) in the treatment group compared to UCCAO rats. Furthermore, long-term TA treatment significantly increased the levels of Nrf2 (P < 0.001), NQO-1 (P < 0.001), and HO-1 (P < 0.001) in the hippocampus of the treatment group compared to the UCCAO group. TA consumption in the treatment group applied its anti-inflammatory effects via reducing the activity of NF-κB and TNF-α in comparison with the UCCAO group (P < 0.001 for both). Blood triglyceride, blood glucose, and liver enzymes did not change considerably in the groups (P > 0.05). The current results indicate that long-term post-treatment of TA exhibits protective effects against memory deficit and motor dysfunction. The cellular mechanism of TA in hypoperfused rats might be associated with the activation of antioxidant pathways, especially the Nrf2 pathway, and suppressing inflammatory factors like NF-κB and TNF-α.