scholarly journals Programmed Cell Death in Cerebral Ischemia

2001 ◽  
Vol 21 (2) ◽  
pp. 99-109 ◽  
Author(s):  
Steven H. Graham ◽  
Jun Chen
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Programmed Cell Death ◽  
Viral Vector ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
Morphologic Change ◽  
Altered Expression ◽  
Ischemic Brain

Programmed cell death (PCD) is an ordered and tightly controlled set of changes in gene expression and protein activity that results in neuronal cell death during brain development. This article reviews the molecular pathways by which PCD is executed in mammalian cells and the potential relation of these pathways to pathologic neuronal cell death. Whereas the classical patterns of apoptotic morphologic change often do not appear in the brain after ischemia, there is emerging biochemical and pharmacologic evidence suggesting a role for PCD in ischemic brain injury. The most convincing evidence for the induction of PCD after ischemia includes the altered expression and activity in the ischemic brain of deduced key death-regulatory genes. Furthermore, studies have shown that alterations in the activity of these gene products by peptide inhibitors, viral vector-mediated gene transfer, antisense oligonucleotides, or transgenic mouse techniques determine, at least in part, whether ischemic neurons live or die after stroke. These studies provide strong support for the hypothesis that PCD contributes to neuronal cell death caused by ischemic injury. However, many questions remain regarding the precise pathways that initiate, sense, and transmit cell death signals in ischemic neurons and the molecular mechanisms by which neuronal cell death is executed at different stages of ischemic injury. Elucidation of these pathways and mechanisms may lead to the development of novel therapeutic strategies for brain injury after stroke and related neurologic disorders.

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

Upregulated miR-29b promotes neuronal cell death by inhibiting Bcl2L2 after ischemic brain injury

2011 ◽  
Vol 216 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Guodong Shi ◽  
Yang Liu ◽  
Tielong Liu ◽  
Wangjun Yan ◽  
Xiaowei Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals Dipyrone Inhibits Neuronal Cell Death and Diminishes Hypoxic/Ischemic Brain Injury

Neurosurgery ◽  
2011 ◽  
Vol 69 (4) ◽  
pp. 942-956 ◽  
Author(s):  
Yi Zhang ◽  
Xin Wang ◽  
Sergei V Baranov ◽  
Shan Zhu ◽  
Zhihong Huang ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

The LPA-CDK5-Tau Pathway Mediates Neuronal Injury in an In Vitro Model of Ischemia-Reperfusion Insult

2021 ◽  
Author(s):  
Yaya Wang ◽  
Jie Zhang ◽  
Liqin Huang ◽  
Yanhong Mo ◽  
Changyu Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain ◽  
Pathophysiological Process ◽  
Vitro Model

Abstract Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

scholarly journals Disruption of Bax Protein Prevents Neuronal Cell Death but Produces Cognitive Impairment in Mice following Traumatic Brain Injury

2008 ◽  
Vol 25 (7) ◽  
pp. 755-767 ◽  
Author(s):  
Roya Tehranian ◽  
Marie E. Rose ◽  
Vincent Vagni ◽  
Alicia M. Pickrell ◽  
Raymond P. Griffith ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Death ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Bax Protein

Abstract W P210: Plasma Kallikrein Induces Ischemic Brain Damage Through Cleavage-Dependent Activation of NMDA Receptors

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Gongxiong wu ◽  
Long-Jun Wu ◽  
David E. Clapham ◽  
Edward P. Feener
Keyword(s):  
Cell Culture ◽  
Cell Death ◽  
Ischemic Stroke ◽  
Nmda Receptor ◽  
Brain Damage ◽  
Infarct Volume ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Plasma Kallikrein ◽  
Ischemic Brain

Background and Purpose: Ischemic stroke ultimately leads to brain dysfunction and neurological deficits. However, the mechanisms that contribute to neuronal injury and dysfunction in ischemic stroke are not fully understood. Recent studies have shown that pharmacological inhibition of the serine protease plasma kallikrein (PK) reduced neuron death and neurological impairment in ischemic brain in mice. In this study, we examine the effects of PK on the neuronal cell death and brain damage in mice and investigate the molecular mechanism of PK-induced neuronal cell death in ischemic stroke. Methods: Ischemia was produced in wild-type (WT) and PK knockout mice by permanent middle cerebral artery occlusion (pMCAO). Infarct volume was quantified by TTC staining and brain function was evaluated by neurological scoring. The effect of PK on neuron cell death in cell culture was determined by lactate dehydrogenase (LDH) release. NMDA receptor function was measured by patch clamp and Ca2+ imaging. NR1 cleavage was detected by western blot. The effect of systemic PK inhibition on pMCAO-induced infarct volume was evaluated in mice treated with the PK inhibitor (BPCCB) or vehicle alone delivered using subcutaneously implanted osmotic pumps. Results: We show that PK deficiency in mice decreased MCAO-induced infarct volume by 39.8% (P<0.01) and improved neurological function compared responses in WT mice. Addition of PK to cell culture media enhanced NMDA-induced cell death of cortical neurons. We further show that PK induced cleavage of NR1 and identify the cleavage site in the extracellular N-terminal domain of NR1. The truncated form of NR1 displayed enhanced NMDA-stimulated current and calcium influx. Treatment of mice with a PK inhibitor reduced MCAO-induced brain damage and neuronal injury. Conclusions: PK enhances NMDA receptor-mediated excitotoxicity and ischemic neuronal death. These findings suggest that PK may serve as a potential therapeutic target for treatment of ischemic stroke.

Su.54. Programmed Cell Death-1 Regulates Neuronal Cell Death in the Developing Mouse Retina

2008 ◽  
Vol 127 ◽  
pp. S141-S142
Author(s):  
Caroline Sham ◽  
Ling Chen ◽  
Yin Wu ◽  
Arlene Sharpe ◽  
Gordon Freeman ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Mouse Retina ◽  
Programmed Cell Death 1
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