Peroxisome proliferator-activated receptor-γ doesn't modify altered electrophysiological properties of the CA1 pyramidal neurons in a rat model of hepatic cirrhosis.

Regarding the low quality of life due to the cognitive complications in the patients with hepatic cirrhosis (HC), the goal of this study was to examine the possible neuroprotective effect of pioglitazone (PIO) on the electrophysiological alterations of hippocampus, a major area of cognition, in the experimental model of bile duct ligation (BDL). We used adult male Wistar rats in the present study to perform BDL or sham surgery. Pioglitazone was administered in BDL rats two weeks after the surgery for the next continuous four weeks. The effects of pioglitazone on BDL-induced electrophysiological alterations of the CA1 pyramidal neurons in the hippocampus were evaluated by whole-cell patch clamp recordings. Our findings demonstrated that chronic administration of PIO could not reverse the electrophysiological changes in the CA1 pyramidal neurons of the hippocampus in BDL rats but could improve the hepatic dysfunction.Together, the results of this study suggest that PIO administration cannot counteract altered intrinsic properties of the hippocampal neurons which has been shown recently as an involved mechanism of the cognitive impairments in hepatic encephalopathy (HE).

The effects of minocycline on proliferation, differentiation and migration of neural stem/progenitor cells.

Purpose: There are several attempts to enhance the capacities of neural stem/progenitor cells (NS/PCs) as a probable source of stem cell therapy for neurodegerative diseases. The evidence shows that minocycline has several non-antibacterial effects in neurodegenerative diseases. We aimed to investigate the effect of minocycline on proliferation, differentiation and migration of embryonic NS/PCs.Materials and methods: NS/PCs extracted from ganglionic eminence of 13.5-day embryonic mice were cultured according to neurosphere protocol. After second passage they were exposed to different doses of minocycline for 7 days. The number and diameter of neurospheres were assessed to evaluate their proliferation. Migration was estimated based on the distances traveled by the cells. Because of the importance of NS/PCs behaviors in 3-dimentional environment, all assessments were done in 3-dimentional and 2-dimentional cultures. Moreover, the fate of NS/PCs to neuron or glial cells was studied.Results: NS/PCs exposed to 1 µg/ml and 10 µg/ml of minocycline and those in untreated group traveled significantly longer distances compared to those treated with 50 µg/ml and 100 µg/ml of minocycline. In addition, higher doses of minocycline reduced the NS/PCs proliferation remarkably compared to control condition just in 2-D culture. However, the differentiation capacity of cells was not significantly affected by 1 and 10 µg/ml of minocycline.Conclusion: The behavior of NS/PCs depends on minocycline dose as well as the characteristics of environment.

Ischemic Postconditioning Attenuates Bilateral Renal Ischemia-induced Cognitive Impairments.

Introduction: Acute Kidney Injury (AKI) is a frequent complication of kidney failure with high mortality, leading to brain dysfunction. This study aimed to investigate the possible protective effect of Ischemic Postconditioning (IPo) against brain dysfunction induced by Bilateral Renal Ischemia (BRI). Methods: Male Wistar rats underwent BRI, sham, or IPo surgery 24h and 1w after reperfusion. The rats' explorative behaviors and motor function were evaluated by an open field, rotarod, and wire grip tests. The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Western blotting was performed to evaluate hippocampal Brain-Derived Neurotrophic Factor (BDNF) expression. Results: The impairment of balance function induced by BRI was not reversed; however, passive avoidance learning impairment was reversed by postconditioning 24h after reperfusion. IPo increased muscle strength compared to the BRI group; however, explorative behaviors and balance function had no difference 1w after reperfusion. BRI significantly decreased the BDNF protein expression in the hippocampus, and postconditioning increased 24h after reperfusion. Conclusion: The obtained results demonstrated the deleterious effect of BRI on cognitive and balance function 24h after reperfusion. IPo indicated a curative effect against cognitive dysfunction probably by enhancing BDNF protein expression in the hippocampus. Highlights: IPo improved passive avoidance learning impairment induced by BRI.IPo increased muscle strength compared to the BRI group.BRI significantly decreased the BDNF protein expression in the hippocampus.IPo increased BDNF protein expression 24h after reperfusion. Plain Language Summary: Acute kidney injury may be associated with numerous complications in different regions of brain, as it may alter the permeability of the blood-brain barrier, accumulate the toxins, decreased blood flow to the brain, increased risk of encephalopathy, higher mental dysfunctions like delirium, stroke, memory and thinking problems (dementia) in people with kidney failure. It has been demonstrated that the most common causes of mortality in acute kidney injury is brain dysfunction. Therefore, discovering new treatments can decrease the brain injuries and help the patients with kidney dysfunction to have a higher quality of life. Ischemic postconditioning, which refers to a series of brief ischemia and reperfusion cycles applied immediately at the site of the ischemic organ after reperfusion, results in reduced injuries induced by ischemia. The purpose of the current study was designed to investigate whether ischemic postconditioning exerts neuroprotective effects against brain dysfunctions induced by renal ischemia in rats. Results of this study demonstrated that acute kidney injury triggers distant organ dysfunction and leads to cognitive and balance dysfunction 24h after induction of renal ischemia and ischemic postconditioning protects the brain as a remote organ against cognitive dysfunction from the injury induced by renal ischemia.