Cuprizone Affects Hypothermia-Induced Neuroprotection and Enhanced Neuroblast Differentiation in the Gerbil Hippocampus after Ischemia

Abstract

In the present study, we investigated the effects of cuprizone on cell death, glial activation, and neuronal plasticity induced by hypothermia after ischemia in gerbils. Food was supplemented with cuprizone at 0.2% ad libitum for eight weeks. At six weeks after diet feeing, gerbils received transient forebrain ischemia with or without hypothermic preconditioning. Cuprizone treatment for 8 weeks increased the number of astrocytes, microglia, and pro-inflammatory cytokine levels in the hippocampus. In addition, cuprizone treatment significantly decreased the number of proliferating cells and neuroblasts in the dentate gyrus. Brain ischemia caused cell death, disruption of myelin basic proteins, and reactive gliosis in CA1. In addition, ischemia significantly increased pro-inflammatory cytokines and the number of proliferating cells and differentiating neuroblasts in the dentate gyrus. In contrast, hypothermic conditioning attenuated these changes in CA1 and the dentate gyrus. However, cuprizone treatment decreased cell survival induced by hypothermic preconditioning after ischemia and increased the number of reactive microglia and astrocytes in CA1 as well as that of macrophages in the subcallosal zone. These changes occurred because the protective effect of hypothermia in ischemic damage was disrupted by cuprizone administration. Furthermore, cuprizone decreased ischemia-induced proliferating cells and neuroblasts in the dentate gyrus.

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

“…Animals were anesthetized with 2.5% isoflurane (Baxter, Deerfield, IL, USA) and then carotid arteries were isolated from adjacent tissue and occluded using aneurysm clips for 5 min as previously reported [ 57 ]. Blood flow through carotid arteries was monitored in the central artery of the retinae using an ophthalmoscope (HEINE K180 ® ; HEINE Optotechnik, Herrsching, Germany).…”

“…To show the morphological evidence of the changes in neurons, astrocytes, and microglia in the hippocampus, immunohistochemical staining was conducted for NeuN, GFAP, and Iba-1, respectively, as previously described [ 20 , 57 ]. In addition, proliferating cells and neuroblasts were visualized with the immunohistochemistry of Ki67 and DCX.…”

Tat-Endophilin A1 Fusion Protein Protects Neurons from Ischemic Damage in the Gerbil Hippocampus: A Possible Mechanism of Lipid Peroxidation and Neuroinflammation Mitigation as Well as Synaptic Plasticity

“…Interruption of blood supply rapidly depletes neuronal ATP, but subsequent reperfusion of blood flow markedly increases the formation of reactive oxygen species (ROS) and intracellular transport of Ca 2+ [ 6 , 7 ]. In addition, transient forebrain ischemia increases pro-inflammatory cytokine release from astrocytes and microglia to enhance neuronal damage in the hippocampus [ 8 , 9 ]. Several mechanisms have been proposed for the execution of neuronal damage upon ischemic insult [ 10 , 11 , 12 ]; however, there is a dearth of therapeutic agents owing to their limited ability to cross the blood–brain barrier as well as the cell membrane.…”