scholarly journals Calsenilin Contributes to Neuronal Cell Death in Ischemic Stroke

2012 ◽  
Vol 23 (4) ◽  
pp. 402-412 ◽  
Author(s):  
Jong-Sung Park ◽  
Silvia Manzanero ◽  
Jae-Woong Chang ◽  
Yuri Choi ◽  
Sang-Ha Baik ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke

2016 ◽  
Vol Volume 12 ◽  
pp. 3083-3092 ◽  
Author(s):  
Shengtao Yao ◽  
Bo Tang ◽  
Gang Li ◽  
Ruiming Fan ◽  
Fang Cao
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

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.

scholarly journals Evidence that collaboration between HIF-1α and Notch-1 promotes neuronal cell death in ischemic stroke

2014 ◽  
Vol 62 ◽  
pp. 286-295 ◽  
Author(s):  
Yi-Lin Cheng ◽  
Jong-Sung Park ◽  
Silvia Manzanero ◽  
Yuri Choi ◽  
Sang-Ha Baik ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Notch 1

scholarly journals Calcium/Calmodulin–Dependent Protein Kinase II in Cerebrovascular Diseases

2021 ◽  
Author(s):  
Xuejing Zhang ◽  
Jaclyn Connelly ◽  
Edwin S. Levitan ◽  
Dandan Sun ◽  
Jane Q. Wang
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebrovascular Diseases ◽  
Biological Processes ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein ◽  
The Brain

AbstractCerebrovascular disease is the most common life-threatening and debilitating condition that often leads to stroke. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key Ca2+ sensor and an important signaling protein in a variety of biological systems within the brain, heart, and vasculature. In the brain, past stroke-related studies have been mainly focused on the role of CaMKII in ischemic stroke in neurons and established CaMKII as a major mediator of neuronal cell death induced by glutamate excitotoxicity and oxidative stress following ischemic stroke. However, with growing understanding of the importance of neurovascular interactions in cerebrovascular diseases, there are clearly gaps in our understanding of how CaMKII functions in the complex neurovascular biological processes and its contributions to cerebrovascular diseases. Additionally, emerging evidence demonstrates novel regulatory mechanisms of CaMKII and potential roles of the less-studied CaMKII isoforms in the ischemic brain, which has sparked renewed interests in this dynamic kinase family. This review discusses past findings and emerging evidence on CaMKII in several major cerebrovascular dysfunctions including ischemic stroke, hemorrhagic stroke, and vascular dementia, focusing on the unique roles played by CaMKII in the underlying biological processes of neuronal cell death, neuroinflammation, and endothelial barrier dysfunction triggered by stroke. We also highlight exciting new findings, promising therapeutic agents, and future perspectives for CaMKII in cerebrovascular systems.

scholarly journals miR-214 Alleviates Ischemic Stroke-Induced Neuronal Death by Targeting DAPK1 in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Yan Shi ◽  
Tian Tian ◽  
Er-Li Cai ◽  
Can Yang ◽  
Xin Yang
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Death ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neurological Deficits ◽  
Tunel Staining

BackgroundIschemic stroke induces neuronal cell death and causes brain dysfunction. Preventing neuronal cell death after stroke is key to protecting the brain from stroke damage. Nevertheless, preventative measures and treatment strategies for stroke damage are scarce. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathogenesis of central nervous system (CNS) disorders and may serve as potential therapeutic targets.MethodsA photochemically induced thrombosis (PIT) mouse model was used as an ischemic stroke model. qRT-PCR was employed to assess changes in miRNAs in ischemic lesions of PIT-stroke mice and primary cultured neurons subjected to oxygen-glucose deprivation (OGD). 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate brain infarction tissues in vivo. TUNEL staining was employed to assess neuronal death in vitro. Neurological scores and motor coordination were investigated to evaluate stroke damage, including neurological deficits and motor function.ResultsIn vivo and in vitro results demonstrated that levels of miR-124 were significantly decreased following stroke, whereas changes in death-associated protein kinase 1 (DAPK1) levels exhibited the converse pattern. DAPK1 was identified as a direct target of miR-124. N-methyl-D-aspartate (NMDA) and OGD-induced neuronal death was rescued by miR-124 overexpression. Upregulation of miR-124 levels significantly improved PIT-stroke damage, including the overall neurological function in mice.ConclusionWe demonstrate the involvement of the miR-124/DAPK1 pathway in ischemic neuronal death. Our results highlight the therapeutic potential of targeting this pathway for ischemic stroke.

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