scholarly journals Neuroprotection against Focal Ischemic Brain Injury by Inhibition of c-Jun N-Terminal Kinase and Attenuation of the Mitochondrial Apoptosis-Signaling Pathway

2005 ◽  
Vol 25 (6) ◽  
pp. 694-712 ◽  
Author(s):  
Yanqin Gao ◽  
Armando P. Signore ◽  
Wei Yin ◽  
Guodong Cao ◽  
Xiao-Ming Yin ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Strong Support ◽  
Serine Phosphorylation ◽  
Ischemic Brain Injury ◽  
Mitochondrial Apoptosis ◽  
Ischemic Brain ◽  
Jnk Activation

c-Jun N-terminal kinase (JNK) is an important stress-responsive kinase that is activated by various forms of brain insults. In this study, we have examined the role of JNK activation in neuronal cell death in a murine model of focal ischemia and reperfusion; furthermore, we investigated the mechanism of JNK in apoptosis signaling, focusing on the mitochondrial-signaling pathway. We show here that JNK activity was induced in the brain 0.5 to 24 h after ischemia. Systemic administration of SP600125, a small molecule JNK-specific inhibitor, diminished JNK activity after ischemia and dose-dependently reduced infarct volume. c-Jun N-terminal kinase inhibition also attenuated ischemia-induced expression of Bim, Hrk/DP5, and Fas, but not the expression of Bcl-2 or FasL. In strong support of a role for JNK in promoting the mitochondrial apoptosis-signaling pathway, JNK inhibition prevented ischemia-induced mitochondrial translocation of Bax and Bim, release of cytochrome c and Smac, and activation of caspase-9 and caspase-3. The potential mechanism by which JNK promoted Bax translocation after ischemia was further studied using coimmunoprecipitation, and the results revealed that JNK activation caused serine phosphorylation of 14-3-3, a cytoplasmic sequestration protein of Bax, leading to Bax disassociation from 14-3-3 and subsequent translocation to mitochondria. These results confirm the role of JNK as a critical cell death mediator in ischemic brain injury, and suggest that one of the mechanisms by which JNK triggers the mitochondrial apoptosis-signaling pathway is via promoting Bax and Bim translocation.

scholarly journals Features of pathogenesis and early diagnostic criteria of hypoxic-ischemic brain injury in newborns (part 2)

2021 ◽  
Vol 16 (8) ◽  
pp. 5-14
Author(s):  
V.Yu. Martyniuk ◽  
V.B. Shveikina ◽  
T.K. Znamenska ◽  
L.I. Nikulina
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Injury ◽  
Early Diagnosis ◽  
Intercellular Adhesion ◽  
Developing Brain ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

The article deals with the current problem of neonatology and pediatric neurology — the issues of early diagnosis of perinatal hypoxic-ischemic brain injury in newborns, particularly, in prematurely born children. The work considers modern literature data on the mechanisms of hypoxic-ischemic perinatal brain damage. New data on the functioning, injury, as well as the mechanism of cell death of neuronal and glial origin in the developing brain are presented. It was shown that excitotoxicity (glutamatergic system), oxidative stress and aseptic inflammation are involved in the realization of this mechanism, the final result of which is cell death by necrosis and pathological apoptosis. It was emphasized that in immature neuronal tissue, the death of neurons occurs not only by the above paths, but also due to the combined necrotic-apoptotic (necroptotic) mechanism. The ambiguous role of glutamate receptors in the developing brain is analyzed. Literature data are presented that excitotoxicity, oxidative stress and inflammation against the background of peculiarities mitochondrial functioning in the brain lead to the onset of pathological apoptosis. It has been determined that the most promising in the early diagnosis of hypoxic-ischemic damage to the central nervous system in newborns, in particular premature babies, is the study of the level of neuron-specific proteins and antibodies to them, as well as proteins associated with the plasma membrane — intercellular adhesion molecules. The article analyzes the role of neuronal and glial markers, in particular glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1, myelin basic protein, as well as the role of pro-inflammatory cytokines in the mechanisms of damage to cells of the developing brain. The role of the membrane protein of cerebral capillary endotheliocytes, an intercellular adhesion molecule 1, as one of the markers of damage to the blood-brain barrier cells in various pathological processes, in particular hypoxia and ischemia, was determined.

scholarly journals Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel

2017 ◽  
Vol 14 (4) ◽  
pp. 2937-2942 ◽  
Author(s):  
Lixiao Pan ◽  
Fengyun Yang ◽  
Caixia Lu ◽  
Changxin Jia ◽  
Qing Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals p53-mediated neuronal cell death in ischemic brain injury

2010 ◽  
Vol 26 (3) ◽  
pp. 232-240 ◽  
Author(s):  
Li-Zhi Hong ◽  
Xiao-Yuan Zhao ◽  
Hui-Ling Zhang
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals Hsp70 Overexpression Sequesters AIF and Reduces Neonatal Hypoxic/Ischemic Brain Injury

2005 ◽  
Vol 25 (7) ◽  
pp. 899-910 ◽  
Author(s):  
Yasuhiko Matsumori ◽  
Shwuhuey M Hong ◽  
Koji Aoyama ◽  
Yang Fan ◽  
Takamasa Kayama ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Wild Type ◽  
Hsp 70 ◽  
Artery Ligation ◽  
Ischemic Brain ◽  
Carotid Artery Ligation ◽  
High Level ◽  
Apoptosis Inducing Factor

Apoptosis is implicated in neonatal hypoxic/ischemic (H/I) brain injury among various forms of cell death. Here we investigate whether overexpression of heat shock protein (Hsp) 70, an antiapoptotic protein, protects the neonatal brain from H/I injury and the pathways involved in the protection. Postnatal day 7 (P7) transgenic mice overexpressing rat Hsp70 (Tg) and their wild-type littermates (Wt) underwent unilateral common carotid artery ligation followed by 30 mins exposure to 8% O2. Significant neuroprotection was observed in Tg versus Wt mice on both P12 and P21, correlating with a high level of constitutive but not inducible Hsp70 in the Tg. More prominent injury was observed in Wt and Tg mice on P21, suggesting its continuous evolution after P12. Western blot analysis showed that translocation of cytochrome c, but not the second mitochondria-derived activator of caspase (Smac)/DIABLO and apoptosis-inducing factor (AIF), from mitochondria into cytosol was significantly reduced in Tg 24 h after H/I compared with Wt mice. Coimmunoprecipitation detected more Hsp70 bound to AIF in Tg than Wt mice 24 h after H/I, inversely correlating with the amount of nuclear, but not cytosolic, AIF translocation. Our results suggest that interaction between Hsp70 and AIF might have reduced downstream events leading to cell death, including the reduction of nuclear AIF translocation in the neonatal brains of Hsp70 Tg mice after H/I.

scholarly journals Pathophysiological role of zinc in ischemic brain injury

Oncotarget ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 5670-5671
Author(s):  
Zhifeng Qi ◽  
Ke Jian Liu
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Pathophysiological Role
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