TGF-β1 Protects Hippocampal Neurons Against Degeneration Caused by Transient Global Ischemia

Stroke ◽  
1996 ◽  
Vol 27 (9) ◽  
pp. 1609-1615 ◽  
Author(s):  
P. Henrich-Noack ◽  
J.H.M. Prehn ◽  
J. Krieglstein
Keyword(s):  
Hippocampal Neurons ◽  
Global Ischemia ◽  
Transient Global Ischemia ◽  
Tgf Β1

scholarly journals Cloning and Characterization of Rat Caspase-9: Implications for a Role in Mediating Caspase-3 Activation and Hippocampal Cell Death after Transient Cerebral Ischemia

2002 ◽  
Vol 22 (5) ◽  
pp. 534-546 ◽  
Author(s):  
Guodong Cao ◽  
Yumin Luo ◽  
Tetsuya Nagayama ◽  
Wei Pei ◽  
R. Anne Stetler ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Neuronal Survival ◽  
Global Ischemia ◽  
Adult Brain ◽  
Caspase 8 ◽  
Intrinsic Pathway ◽  
Caspase 9 ◽  
Transient Global Ischemia

Delayed hippocampal neurodegeneration after transient global ischemia is mediated, at least in part, through the activation of terminal caspases, particularly caspase-3, and the subsequent proteolytic degradation of critical cellular proteins. Caspase-3 may be activated by the membrane receptor-initiated caspase-8–dependent extrinsic pathway and the mitochondria-initiated caspase-9–dependent intrinsic pathway; however, the precise role of these deduced apoptosis-signaling pathways in activating caspase-3 in ischemic neurons remains elusive. The authors cloned the caspase-9 gene from the rat brain and investigated its potential role in mediating ischemic neuronal death in a rat model of transient global ischemia. Caspase-9 gene expression and protease activity were extremely low in the adult brain, whereas they were developmentally upregulated in newborn rats, especially at postnatal 12 weeks, a finding consistent with the theory of an essential role for caspase-9 in neuronal apoptosis during brain development. After 15-minute transient global ischemia, caspase-9 was overexpressed and proteolytically activated in the hippocampal CA1 neurons at 8 to 72 hours of reperfusion. The temporal profile of caspase-9 activation coincided with that of cytochrome c release and caspase-3 activation, but preceded CA1 neuronal death. Immunoprecipitation experiments revealed that there was enhanced formation of Apaf-1/caspase-9 complex in the hippocampus 8 and 24 hours after ischemia. Furthermore, intracerebral ventricular infusion of the relatively specific caspase-9 inhibitor N-benzyloxycarbonyl-Leu-Glu-His-Asp-fluoro-methylketone before ischemia attenuated caspase-3–like activity and significantly enhanced neuronal survival in the CA1 sector. In contrast, inhibition of caspase-8 activity had no significant effect on caspase-3 activation or neuronal survival. These results suggest that the caspase-9–dependent intrinsic pathway may be the primary mechanism responsible for the activation of caspase-3 in ischemic hippocampal neurons.

Fos-like immunoreactivity in rat hippocampal neurons following transient global ischemia

1997 ◽  
Vol 19 (1) ◽  
pp. 89-91 ◽  
Author(s):  
Michael Tseng ◽  
Shyue-An Chan ◽  
Kenneth Reid ◽  
Vasudeva Iyer
Keyword(s):  
Hippocampal Neurons ◽  
Global Ischemia ◽  
Transient Global Ischemia

scholarly journals Mild Hypothermia Reduces Zinc Translocation, Neuronal Cell Death, and Mortality after Transient Global Ischemia in Mice

2002 ◽  
Vol 22 (10) ◽  
pp. 1231-1238 ◽  
Author(s):  
Daisuke Tsuchiya ◽  
Shwuhuey Hong ◽  
Sang Won Suh ◽  
Takamasa Kayama ◽  
S. Scott Panter ◽  
...  
Keyword(s):  
Cell Death ◽  
Hippocampal Neurons ◽  
Mild Hypothermia ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Global Ischemia ◽  
Doppler Flowmetry ◽  
Transient Global Ischemia ◽  
Hematoxylin Eosin ◽  
Cortical Perfusion

The authors sought to determine whether Zn2+ translocation associated with neuronal cell death occurs after transient global ischemia (TGI) in mice, as has been previously shown in rats, and to determine the effect of mild hypothermia on this reaction. To validate the TGI model, carbon-black injection and laser-Doppler flowmetry were compared in three strains of mice (C57BL/6, SV129, and HSP70 transgenic mice) to assess posterior communicating artery (PcomA) development and cortical perfusion. In C57BL/6 mice, optimal results were obtained when subjected to 20-minute TGI. Brain and rectal temperature measurements were compared to monitor hypothermia. Results of TGI were compared in normothermia (NT; 37°C) and mild hypothermia groups (HT; 33°C) by staining with Zn2+-specific fluorescent dye, N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) and hematoxylin– eosin 72 hours after reperfusion. The Zn2+ translocation observed in hippocampus CA1, CA2, and Hilus 72 hours after 20 minutes of TGI was significantly reduced by mild hypothermia. The number of degenerating neurons in the HT group was significantly less than in the NT group. Mild hypothermia reduced mortality significantly (7.1% in HT, 42.9% in NT). Results suggest that mild hypothermia may reduce presynaptic Zn2+ release in mice, which protects vulnerable hippocampal neurons from ischemic necrosis. Future studies may further elucidate mechanisms of Zn2+-induced ischemic injury.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal

2019 ◽  
Vol 19 (8) ◽  
pp. 597-604
Author(s):  
Li Pang ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Caspase 3 ◽  
Global Ischemia ◽  
Neurological Deficits ◽  
Global Cerebral Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Transient Global Ischemia

Background: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride. Methods: CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study. Results: CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats. Conclusion: Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.

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