Differential Effects of Pioglitazone in the Hippocampal CA1 Region Following Transient Forebrain Ischemia in Low- and High-Fat Diet-Fed Gerbils

Abstract

In the present study, we investigated the effects of pioglitazone (PGZ) in the hippocampal CA1 region of low- or high-fat diet (LFD or HFD) fed gerbils after transient forebrain ischemia. After 8 weeks of LFD or HFD feeding, PGZ (30 mg/kg) was intraperitoneally administered to the gerbils, following which ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. Administration of PGZ significantly reduced the ischemia-induced hyperactivity 1 day after ischemia/reperfusion in both LFD- and HFD-fed gerbils. At 4 days after ischemia/reperfusion, the neurons were significantly reduced and microglial activation was observed in the hippocampal CA1 region in LFD- and HFD-fed gerbils. The microglial activation was more prominent in the HFD-fed gerbils compared to the LFD-fed gerbils. Administration of PGZ ameliorated ischemia-induced neuronal death and microglial activation in the hippocampal CA1 region 4 days after ischemia/reperfusion in the LFD-fed gerbils, but not in the HFD-gerbils. At 6 h after ischemia/reperfusion, tumor necrosis factor-α (TNF-α) and interlukin-1β (IL-1β) levels were significantly increased in the hippocampal homogenates of LFD-fed group compared to control group, and HFD feeding further increased TNF-α and IL-1β levels. PGZ treatment significantly ameliorated the increase of TNF-α and IL-1β levels in LFD-fed gerbils, not in the HFD-fed gerbils. At 12 h after ischemia/reperfusion, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in hippocampal homogenates were significantly increased in the LFD-fed group compared to the control group, and HFD feeding significantly showed relatively reduction in SOD activity and increase in MDA level. PGZ administration significantly reduced the increase in MDA levels 12 h after ischemia/reperfusion in the LFD-fed gerbils, but not in the HFD-fed gerbils. These results suggest that PGZ ameliorates the neuronal damage induced by ischemia by maintaining the TNF-α, IL-1β, SOD and MDA levels in LFD-fed gerbils. In addition, HFD feeding affects the modulation of these parameters in the hippocampus after transient forebrain ischemia.

Pyridoxine Deficiency Exacerbates Neuronal Damage after Ischemia by Increasing Oxidative Stress and Reduces Proliferating Cells and Neuroblasts in the Gerbil Hippocampus

“…To elucidate the effects of pyridoxine deficiency on lipid peroxidation induced by ischemia, transient forebrain ischemia was induced with occlusion of common carotid arteries, and the animals ( n = 5 per group) were sacrificed at 3, 12, and 24 h after ischemia/reperfusion on the 56th day of diet feeding. Both hippocampi were quickly removed, and MDA levels were measured with a Bioxytech MDA-586 kit (Oxis Research, Portland, OR, USA) as described in the previous study [ 59 ]. MDA levels were normalized to the protein concentration and the assay was triplicated.…”

High fat diet accelerates and exacerbates microgliosis and neuronal damage/death in the somatosensory cortex after transient forebrain ischemia in gerbils

“…We recently reported that the level of blood glucose, triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels were significantly increased in this gerbil model of HFD [ 1 ]. In addition, it has been reported that, in gerbils fed HFD for 8 weeks, body weight, level of blood glucose, triglyceride and total cholesterol are significantly increased compared with gerbils fed ND [ 35 ]. The negative effect of obesity in gerbils was observed after 4–6 months of HFD feeding [ 36 ].…”

“…The negative effect of obesity in gerbils was observed after 4–6 months of HFD feeding [ 36 ]. Above-mentioned authors have reported that ischemia-reperfusion injury exacerbates neuronal damage in the striatum [ 1 ] and septum [ 35 ] of gerbils fed HFD. In the case of rats, HFD feeding for 3 months worsens the outcome of neuronal damage after endothelin-induced ischemia [ 14 ].…”

A 2-Min Transient Ischemia Confers Cerebral Ischemic Tolerance in Non-Obese Gerbils, but Results in Neuronal Death in Obese Gerbils by Increasing Abnormal mTOR Activation-Mediated Oxidative Stress and Neuroinflammation

“…Obesity is a condition characterized by an excessive accumulation of body fat that can lead to metabolic abnormalities, such as hyperlipidemia, hypercholesterolemia, and hyperglycemia, all of which can affect the pathophysiology of ischemic insults [33,34]. In this study, we set up a HFD-induced obese gerbil model to investigate effects of a 2-min TI on the neuronal damage in the hippocampus of HFD-induced obese gerbils.…”