Aging is Neuroprotective During Global Ischemia but Leads to Increased Caspase-3 and Apoptotic Activity in Hippocampal Neurons

2006 ◽  
Vol 3 (3) ◽  
pp. 181-186 ◽  
Author(s):  
Zhen He ◽  
James Meschia ◽  
Thomas Brott ◽  
Dennis Dickson ◽  
Michael Mckinney
Keyword(s):  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Global Ischemia ◽  
Apoptotic Activity

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.

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.

Survivin expression in correlation with apoptotic activity in canine lymphomas

2017 ◽  
Vol 20 (2) ◽  
pp. 329-338 ◽  
Author(s):  
J. Sokołowska ◽  
K. Urbańska
Keyword(s):  
Cell Cycle ◽  
Caspase 3 ◽  
Survivin Expression ◽  
Human Tumor ◽  
Apoptotic Index ◽  
Dual Function ◽  
Mean Values ◽  
Apoptotic Markers ◽  
Apoptotic Activity ◽  
Hodgkin's Lymphomas

AbstractSurvivin regulates cell cycle and mitosis and has antiapoptotic properties. Because of its dual function survivin has been the subject of much research focusing on its role in tumorigenesis and the relationship between survivin expression and apoptotic and/or proliferative activity in many types of human tumor including non-Hodgkin’s Lymphomas. Such studies have not been conducted in canine lymphomas. The aim of this study was to evaluate the expression of survivin in canine lymphomas of low (5/25) and high (20/25) grades in relation to apoptotic markers (apoptotic index and index of caspase-3). Survivin was found in all examined lymphomas. Most tumors (18/25) showed survivin expression in 10%-25% of positive cells. Only in single cases was lower (0-10% positive cells, 1/25) or higher (25%-50% and >50% positive cells, 5/25 and 1/25, respectively) survivin expression. No significant differences between mean values of either index of survivin or apoptotic index was found between low and high grade lymphomas. However, such a difference among lymphoma grades was shown regarding the caspase-3 index. No correlation between the survivin index and either the apoptotic index or caspase-3 index was found, irrespective of the method of quantification: in whole specimens or in areas of low and high survivin expression. Positive correlation was consistently noted only between both apoptotic markers. The results indicate that survivin is commonly expressed in canine lymphomas. It seems that survivin does not exhibit anti-apoptotic activity in canine lymphomas. Lack of correlation between survivin expression and apoptotic markers could indicate its potential role in cell cycle activation in lymphoma cells.

scholarly journals Global ischemia induces lysosomal-mediated degradation of mTOR and activation of autophagy in hippocampal neurons destined to die

2016 ◽  
Vol 24 (2) ◽  
pp. 317-329 ◽  
Author(s):  
Jee-Yeon Hwang ◽  
Michael Gertner ◽  
Fabrizio Pontarelli ◽  
Brenda Court-Vazquez ◽  
Michael Vander Laan Bennett ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Global Ischemia

Postischemic hypothermia induced by eugenol protects hippocampal neurons from global ischemia in gerbils

1998 ◽  
Vol 254 (2) ◽  
pp. 101-104 ◽  
Author(s):  
Moo Ho Won ◽  
Jae Chul Lee ◽  
Yung Hi Kim ◽  
Dong Keun Song ◽  
Hong Won Suh ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Global Ischemia

scholarly journals Key Role of Cytochrome C for Apoptosis Detection Using Raman Microimaging in an Animal Model of Brain Ischemia with Insulin Treatment

2019 ◽  
Vol 73 (10) ◽  
pp. 1208-1217 ◽  
Author(s):  
Vanessa Russo ◽  
Patrizio Candeloro ◽  
Natalia Malara ◽  
Gerardo Perozziello ◽  
Michelangelo Iannone ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Brain Ischemia ◽  
Hippocampal Neurons ◽  
Apoptotic Cell ◽  
Resonant Scattering ◽  
Global Ischemia ◽  
Alternative Mechanism ◽  
Mongolian Gerbils ◽  
Incident Wavelength

Brain ischemia represents a leading cause of death and disability in industrialized countries. To date, therapeutic intervention is largely unsatisfactory and novel strategies are required for getting better protection of neurons injured by cerebral blood flow restriction. Recent evidence suggests that brain insulin leads to protection of neuronal population undergoing apoptotic cell death via modulation of oxidative stress and mitochondrial cytochrome c (CytC), an effect to be better clarified. In this work, we investigate on the effect of insulin given intracerebroventricular (ICV) before inducing a transient global ischemia by bilateral occlusion of the common carotid arteries (BCCO) in Mongolian gerbils (MG). The transient (3 min) global ischemia in MG is observed to produce neurodegenerative effect mainly into CA3 hippocampal region, 72 h after cerebral blood restriction. Intracerebroventricular microinfusion of insulin significantly prevents the apoptosis of CA3 hippocampal neurons. Histological observation, after hematoxylin and eosin staining, puts in evidence the neuroprotective role of insulin, but Raman microimaging provides a clearer insight in the CytC mechanism underlying the apoptotic process. Above all, CytC has been revealed to be an outstanding, innate Raman marker for monitoring the cells status, thanks to its resonant scattering at 530 nm of incident wavelength and to its crucial role in the early stages of cells apoptosis. These data support the hypothesis of an insulin-dependent neuroprotection and antiapoptotic mechanism occurring in the brain of MG undergoing transient brain ischemia. The observed effects occurred without any peripheral change on serum glucose levels, suggesting an alternative mechanism of insulin-induced neuroprotection.

Spontaneous tumor apoptosis, caspase 3 and the survival outcome in medulloblastoma patients treated by postoperative radiotherapy and chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14136-14136
Author(s):  
F. Santek ◽  
L. Markulin-Grgic ◽  
R. Kusec
Keyword(s):  
Mitotic Index ◽  
Caspase 3 ◽  
Postoperative Radiotherapy ◽  
Apoptotic Index ◽  
Treatment Modalities ◽  
Rank Test ◽  
Spontaneous Tumor ◽  
The Mean ◽  
Apoptotic Activity ◽  
Index Ratio

14136 Background: The role of apoptosis in neurooncology is still an unexplored area. Only a small number of studies which have combined clinically relevant data and treatment modalities, with the apoptotic activity have been published. Methods: The influence of spontaneous tumor apoptosis and its potential regulators caspase 3, BAX, p53 and bcl-2 was analyzed in 30 medulloblastoma patients with a long follow-up period, after the treatment at the Clinic of Oncology and Radiotherapy by postoperative radiotherapy with or without postirradiational chemotherapy. The mean apoptotic and mitotic index ratio (AI/MI) was measured in all tumor samples obtained by the initial neurosurgical procedure. Results: Significantly different survival groups of adequately treated patients were found only if the apoptotic indexes measured by the morphometrical analyzes (AIM) had been correlated with the TUNEL-essay results (AIT) in the same tumor sample, (log rank test=2.0287, p=0.04). The mean apoptotic index measured in the described combined way had slightly higher values AIM+T=38.2±20.3 (median=32.0), than when measured only by morphometrical analysis AM=23.9±24.9 (median=15.0). In the multivariate analysis according, the most relevant variables were the disease free interval (p<0.001) and the number of CT cycles (0.005<p<0.01). Further parameters of significance were the modality of postoperative radiotherapy, and the general condition of patients measured according to the WHO grading system at the end of treatment (p<0.001) as well as on the late controls, ater completion of the treatment (p<0.001) Conclusions: Our expirience in evaluating the metodology of apoptotic index measurement has confirmed the advantage of combined method of detection of the apoptotic index AIM+T over the use of each of the described methods alone. The apoptotic index has shown a significant influence on survival of the medulloblastoma patients only when divided with the mitotic index MI. Using clinical data of our medulloblastoma patients, the index of apoptosis alone as a prognostic factor has not appeared to be of significant relevance. No significant financial relationships to disclose.

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