scholarly journals Methane-Rich Saline Alleviates CA/CPR Brain Injury by Inhibiting Oxidative Stress, Microglial Activation-Induced Inflammatory Responses, and ER Stress-Mediated Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ruixia Cui ◽  
Sinan Liu ◽  
Cong Wang ◽  
Tong Liu ◽  
Jie Ren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Brain Injury ◽  
Er Stress ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Brain injury induced by cardiac arrest/cardiopulmonary resuscitation (CA/CPR) is the leading cause of death among patients who have recovery of spontaneous circulation (ROSC). Inflammatory response, apoptosis, and oxidative stress are proven pathological mechanisms implicated in neuronal damage. Methane-rich saline (MRS) has been proven that exerts a beneficial protectiveness impact in several models of ischemia-reperfusion injury. The goal of this paper is to ascertain the role of MRS in CA/CPR-induced brain injury and its potential mechanisms. The tracheal intubation of Sprague-Dawley (SD) rats was clamped for 6 min to establish an asphyxiating cardiac arrest model. After that, chest compressions were applied; then, MRS or saline was administered immediately post-ROSC, the rats were sacrificed, and brain tissue was collected at the end of 6 hours. We observed that MRS treatment attenuated neuronal damage in the hippocampal CA1 region by inhibiting microglial activation, leading to a decrease in the overexpression of proinflammatory cytokines such as TNF-α, IL-6, and iNOS. The results also illustrated that MRS treatment diminished apoptosis in the hippocampal CA1 region , reduced the expression of apoptosis-associated proteins Bax and cleaved caspase9, and increased Bcl-2 expression, as well as inhibited the expression of endoplasmic reticulum (ER) stress pathway-related proteins GRP78, ATF4, and CHOP. Further findings showed that MRS treatment significantly attenuated hippocampal ROS and MDA levels and increased GSH and SOD antioxidant factor levels, which indicated that MRS treatment could inhibit oxidative stress. Our results suggest that MRS exerts a protective effect against CA/CPR brain injury, by inhibiting oxidative stress, microglial activation-induced inflammatory responses, and ER stress-mediated apoptosis.

scholarly journals Postischemic Administration of Idazoxan, an α-2 Adrenergic Receptor Antagonist, Decreases Neuronal Damage in the Rat Brain

1989 ◽  
Vol 9 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Ingvar Gustafson ◽  
Yoshitoyo Miyauchi ◽  
Tadeusz W. Wieloch
Keyword(s):  
Cardiac Arrest ◽  
Receptor Antagonist ◽  
Adrenergic Receptor ◽  
Neuronal Damage ◽  
Dorsal Hippocampus ◽  
Histopathological Examination ◽  
Forebrain Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

The effect of an α-2 receptor antagonist, idazoxan, on ischemic neuronal damage in the hippocampus and neocortex was studied in rats following 10 min of forebrain ischemia. Idazoxan was given 0.1 mg/kg i. v. immediately after recirculation, followed by 48 h of continuous infusion at a rate of 10 μg/kg/min. A histopathological examination of the CA1 region of the dorsal hippocampus and neocortex from each hemisphere was made on paraffin-embedded sections following 7 days of survival. In ischemic animals receiving an infusion of saline, 71% of the neurons in the hippocampal CA1 region were degenerated. In contrast, in the idazoxan-treated animals only 31% of the neurons were irreversibly damaged (p < 0.01). We conclude that postischemic administration of the α-2 antagonist idazoxan protects neurons against damage following cerebral ischemia. Rapid postischemic administration of α-2 adrenergic receptor antagonists could be an effective treatment after stroke and cardiac arrest.

scholarly journals Probucol Attenuates Oxidative Stress, Energy Starvation, and Nitric Acid Production Following Transient Forebrain Ischemia in the Rat Hippocampus

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Abdulhakeem A. Al-Majed
Keyword(s):  
Oxidative Stress ◽  
Neuronal Damage ◽  
Lipid Lowering ◽  
Albino Rats ◽  
Forebrain Ischemia ◽  
Energy Depletion ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Oxidative stress and energy depletion are believed to participate in hippocampal neuronal damage after forebrain ischemia. This study has been initiated to investigate the potential neuroprotective effects of probucol, a lipid-lowering drug with strong antioxidant properties, against transient forebrain ischemia-induced neuronal damage and biochemical abnormalities in rat hippocampal CA1 region. Adult male Wistar albino rats were subjected to forebrain ischemia and injected with probucol for the next 7 successive days, and compared to controls. Forebrain ischemia resulted in a significant decrease in the number of intact neurons (77%), glutathione (GSH), and adenosine triphosphate (ATP), and a significant increase in thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite, (NOx) production in hippocampal tissues. The administration of probucol attenuated forebrain ischemia-induced neuronal damage, manifested as a complete reversal of the decrease in the number of intact neurons, ATP and GSH and the increase in TBARS and NOxin hippocampal tissues. This study demonstrates that probucol treatment abates forebrain ischemia-induced hippocampal neuronal loss, energy depletion, and oxidative stress in hippocampal CA1 region. Thus, probucol could be a promising neuroprotective agent in the treatment of forebrain ischemia.

High intrinsic oxidative stress may underlie selective vulnerability of the hippocampal CA1 region

2005 ◽  
Vol 140 (1-2) ◽  
pp. 120-126 ◽  
Author(s):  
Xinkun Wang ◽  
Ranu Pal ◽  
Xue-wen Chen ◽  
Nanteetip Limpeanchob ◽  
Keshava N. Kumar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Selective Vulnerability ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

scholarly journals P27 Protects Neurons from Ischemic Damage by Suppressing Oxidative Stress and Increasing Autophagy in the Hippocampus

2020 ◽  
Vol 21 (24) ◽  
pp. 9496
Author(s):  
Woosuk Kim ◽  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Yeo Sung Yoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Ht22 Cells ◽  
H2o2 Treatment ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 μM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 μM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.

scholarly journals Protective Effect of a Prosaposin-Derived, 18-Mer Peptide on Slowly Progressive Neuronal Degeneration after Brief Ischemia

2001 ◽  
Vol 21 (11) ◽  
pp. 1295-1302 ◽  
Author(s):  
Fumio Morita ◽  
Tong-Chun Wen ◽  
Junya Tanaka ◽  
Ryuji Hata ◽  
Junzo Desaki ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Avoidance Task ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 Neurons ◽  
Saposin C ◽  
Hippocampal Ca1

Slowly progressive degeneration of the hippocampal CA1 neurons was induced by 3-minute transient global ischemia in gerbils. Sustained degeneration of hippocampal CA1 neurons was evident 1 month after ischemia. To investigate the effects of an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain (18MP) on this sustained neuronal degeneration, an intracerebroventricular 18MP infusion was initiated 3 days after ischemia. Histopathologic and behavior evaluations were conducted 1 week and 1 month after induction of ischemia. When compared with the vehicle infusion, 18MP treatment significantly increased the response latency time in a passive avoidance task. Increased neuronal density was also evident, as was the number of intact synapses in the hippocampal CA1 region at 1 week and 1 month after ischemia. 18MP treatment also significantly decreased the number of TUNEL-positive CA1 neurons 1 week after ischemia. Subsequent in vitro experiments using cultured neurons demonstrated that the 18MP at optimal extracellular concentrations of 1 to 100 fg/mL prevented nitric oxide–induced neuronal damage as expected and significantly up-regulated the expressions of bcl-xL mRNA and its translated protein. These results suggest that the gerbil model of 3-minute ischemia is useful in studying the pathogenesis of slowly progressive neuronal degeneration after stroke and in evaluating effects of novel therapeutic agents. It is likely that the 18MP at low extracellular concentrations prevents neuronal apoptosis possibly through up-regulation of the mitochondrial antiapoptotic factor Bcl-xL.

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