Caffeine Releasable Stores of Ca2+ Show Depletion Prior to the Final Steps in Delayed CA1 Neuronal Death

2004 ◽  
Vol 92 (5) ◽  
pp. 2960-2967 ◽  
Author(s):  
Hong Xing ◽  
Aryan Azimi-Zonooz ◽  
C. William Shuttleworth ◽  
John A. Connor
Keyword(s):  
Endoplasmic Reticulum ◽  
Neuronal Death ◽  
Carotid Arteries ◽  
Cell Function ◽  
Mean Amplitude ◽  
Delayed Neuronal Death ◽  
Ischemic Insult ◽  
Cell Degeneration ◽  
Ca1 Neurons ◽  
The Mean

In addition to their role in signaling, Ca2+ ions in the endoplasmic reticulum also regulate important steps in protein processing and trafficking that are critical for normal cell function. Chronic depletion of Ca2+ in the endoplasmic reticulum has been shown to lead to cell degeneration and has been proposed as a mechanism underlying delayed neuronal death following ischemic insults to the CNS. Experiments here have assessed the relative content of ryanodine receptor-gated stores in CA1 neurons by measuring cytoplasmic Ca2+ increases induced by caffeine. These measurements were performed on CA1 neurons, in slice, from normal gerbils, and compared with responses from this same population of neurons 54–60 h after animals had undergone a standard ischemic insult: 5-min bilateral occlusion of the carotid arteries. The mean amplitude of responses in the postischemic population were less than one-third of those in control or sham-operated animals, and 35% of the neurons from postischemic animals showed very small responses that were ∼10% of the control population mean. Refilling of these stores after caffeine challenges was also impaired in postischemic neurons. These observations are consistent with our earlier finding that voltage-gated influx is sharply reduced in postischemic in CA1 neurons and the hypothesis that the resulting depletion in endosomal Ca2+ is an important cause of delayed neuronal death.

scholarly journals DNA Fragmentation Follows Delayed Neuronal Death in CA1 Neurons Exposed to Transient Global Ischemia in the Rat

1997 ◽  
Vol 17 (9) ◽  
pp. 967-976 ◽  
Author(s):  
Carol K. Petito ◽  
Jorge Torres-Munoz ◽  
Brenda Roberts ◽  
John-Paul Olarte ◽  
Thaddeus S. Nowak ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Neuronal Death ◽  
Nuclear Dna ◽  
P53 Protein ◽  
Global Ischemia ◽  
Delayed Neuronal Death ◽  
Ca1 Neurons ◽  
Morphological Studies ◽  
Eosinophilic Cytoplasm

Apoptosis is an active, gene-directed process of cell death in which early fragmentation of nuclear DNA precedes morphological changes in the nucleus and, later, in the cytoplasm. In ischemia, biochemical studies have detected oligonucleosomes of apoptosis whereas sequential morphological studies show changes consistent with necrosis rather than apoptosis. To resolve this apparent discrepancy, we subjected rats to 10 minutes of transient forebrain ischemia followed by 1 to 14 days of reperfusion. Parameters evaluated in the CA1 region of the hippocampus included morphology, in situ end labeling (ISEL) of fragmented DNA, and expression of p53. Neurons were indistinguishable from controls at postischemic day 1 but displayed cytoplasmic basophilia or focal condensations at day 2; some neurons were slightly swollen and a few appeared normal. In situ end labeling was absent. At days 3 and 5, approximately 40 to 60% of CA1 neurons had shrunken eosinophilic cytoplasm and pyknotic nuclei, but only half of these were ISEL. By day 14, many of the necrotic neurons had been removed by phagocytes; those remaining retained mild ISEL. Neither p53 protein nor mRNA were identified in control or postischemic brain by in situ hybridization with riboprobes or by northern blot analysis. These results show that DNA fragmentation occurs after the development of delayed neuronal death in CA1 neurons subjected to 10 minutes of global ischemia. They suggest that mechanisms other than apoptosis may mediate the irreversible changes in the CA1 neurons in this model.

Delayed Neuronal Death is Induced without Postischemic Hyperexcitability: Continuous Multiple-Unit Recording from Ischemic CA1 Neurons

1991 ◽  
Vol 11 (5) ◽  
pp. 819-823 ◽  
Author(s):  
Hitoshi Imon ◽  
Akira Mitani ◽  
Yasushi Andou ◽  
Tatsuru Arai ◽  
Kiyoshi Kataoka
Keyword(s):  
Mongolian Gerbil ◽  
Neuronal Death ◽  
Delayed Neuronal Death ◽  
Unit Recording ◽  
Ca1 Neurons ◽  
Chronic Stage ◽  
Neuronal Hyperexcitability ◽  
Multiple Unit ◽  
Complex Spikes ◽  
Unit Spike

It has been proposed that neuronal hyperexcitability during postischemic chronic stage mediates delayed neuronal death in the hippocampal CA1 region. In the present study, multiple-unit spike discharges were continuously recorded from hippocampal CA1 neurons of the awake Mongolian gerbil for 5 days after 5 min of ischemia. Before ischemia, CA1 neurons showed burst-like spike discharges (so-called complex spikes). Spike discharges disappeared 8–40 s after the onset of 5-min ischemia and reappeared 5–30 min after recirculation. The frequency of discharges gradually increased but did not return to the preischemic level. The amplitude of the spike discharges was smaller than that recorded before ischemia and the number of spikes composing the burst-like discharges diminished. CA1 neurons did not show any hyperexcitability for 5 days. However, histological examinations revealed widespread neuronal death in the CA1 region. These results indicate that the delayed neuronal death in the hippocampal CA1 region is induced without postischemic neuronal hyperexcitability.

scholarly journals The Translational Repressor eIF4E-Binding Protein 2 (4E-BP2) Correlates with Selective Delayed Neuronal Death after Ischemia

2013 ◽  
Vol 33 (8) ◽  
pp. 1173-1181 ◽  
Author(s):  
María Irene Ayuso ◽  
Emma Martínez-Alonso ◽  
Cristina Cid ◽  
Maria Alonso de Leciñana ◽  
Alberto Alcázar
Keyword(s):  
Neuronal Death ◽  
Neuronal Apoptosis ◽  
Binding Protein ◽  
Ischemia Reperfusion ◽  
Initiation Factor ◽  
Delayed Neuronal Death ◽  
Ca1 Neurons ◽  
Translation Inhibition ◽  
Translational Repressor ◽  
Ca1 Region

Transient brain ischemia induces an inhibition of translational rates and causes delayed neuronal death in selective regions and cognitive deficits, whereas these effects do not occur in resistant areas. The translational repressor eukaryotic initiation factor (elF) 4E-binding protein-2 (4E-BP2) specifically binds to eIF4E and is critical in the control of protein synthesis. To link neuronal death to translation inhibition, we study the eIF4E association with 4E-BP2 under ischemia reperfusion in a rat model of transient forebrain ischemia. Upon reperfusion, a selective neuronal apoptosis in the hippocampal cornu ammonis 1 (CA1) region was induced, while it did not occur in the cerebral cortex. Confocal microscopy analysis showed a decrease in 4E-BP2/eIF4E colocalization in resistant cortical neurons after reperfusion. In contrast, in vulnerable CA1 neurons, 4E-BP2 remains associated to eIF4E with a higher degree of 4E-BP2/eIF4E colocalization and translation inhibition. Furthermore, the binding of a 4E-BP2 peptide to eIF4E induced neuronal apoptosis in the CA1 region. Finally, pharmacological-induced protection of CA1 neurons inhibited neuronal apoptosis, decreased 4E-BP2/eIF4E association, and recovered translation. These findings documented specific changes in 4E-BP2/eIF4E association during ischemic reperfusion, linking the translation inhibition to selective neuronal death, and identifying 4E-BP2 as a novel target for protection of vulnerable neurons in ischemic injury.

scholarly journals Delayed Neuronal Death by Transient Ligations of Bilateral Carotid Arteries in SHRSR, SHRSP and WKY

1989 ◽  
Vol 30 (4) ◽  
pp. 582-582 ◽  
Author(s):  
Wei-guo Qiang ◽  
Katsumi Ikeda ◽  
Yasuo Nara ◽  
Ryoichi Horie ◽  
Yukio Yamori
Keyword(s):  
Neuronal Death ◽  
Carotid Arteries ◽  
Delayed Neuronal Death ◽  
Bilateral Carotid

scholarly journals The Upregulation of Glial Glutamate Transporter-1 Participates in the Induction of Brain Ischemic Tolerance in Rats

2007 ◽  
Vol 27 (7) ◽  
pp. 1352-1368 ◽  
Author(s):  
Min Zhang ◽  
Wen-Bin Li ◽  
Jin-Xia Geng ◽  
Qing-Jun Li ◽  
Xiao-Cai Sun ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Pyramidal Neurons ◽  
Glutamate Transporter ◽  
Protective Role ◽  
Ischemic Tolerance ◽  
Delayed Neuronal Death ◽  
Ischemic Insult ◽  
Glial Glutamate Transporter ◽  
Glutamate Transporter 1

Glial glutamate transporter-1 (GLT-1) plays an essential role in removing glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), the present study was undertaken to observe in vivo changes in the expression of GLT-1 and glial fibrillary acidic protein (GFAP) in the CA1 hippocampus during the induction of BIT, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of BIT in rats. Immunohistochemistry for GFAP showed that the processes of astrocytes were prolonged after a CIP 2 days before the lethal ischemic insult, which could protect pyramidal neurons in the CA1 hippocampus against delayed neuronal death induced normally by lethal ischemic insult. The prolonged processes extended into the area between the pyramidal neurons and tightly surrounded them. These changes made the pyramidal layer look like a ‘shape grid’. Simultaneously, the prolonged and extended processes showed a great deal of GLT-1. Western blotting analysis showed significant upregulation of GLT-1 expression after the CIP, especially when it was administered 2 days before the subsequent lethal ischemic insult. Neuropathological evaluation by thionin staining showed that DHK dose-dependently blocked the protective role of CIP against delayed neuronal death induced normally by lethal brain ischemia. It might be concluded that the surrounding of pyramidal neurons by astrocytes and upregulation of GLT-1 induced by CIP played an important role in the acquisition of the BIT induced by CIP.

Bradykinin Postconditioning Protects Pyramidal CA1 Neurons Against Delayed Neuronal Death in Rat Hippocampus

2009 ◽  
Vol 29 (6-7) ◽  
pp. 871-878 ◽  
Author(s):  
Viera Danielisová ◽  
Miroslav Gottlieb ◽  
Miroslava Némethová ◽  
Petra Kravčuková ◽  
Iveta Domoráková ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Rat Hippocampus ◽  
Delayed Neuronal Death ◽  
Ca1 Neurons

scholarly journals Interleukin 3 Prevents Delayed Neuronal Death in the Hippocampal CA1 Field

1998 ◽  
Vol 188 (4) ◽  
pp. 635-649 ◽  
Author(s):  
Tong-Chun Wen ◽  
Junya Tanaka ◽  
Hui Peng ◽  
Junzo Desaki ◽  
Seiji Matsuda ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Delayed Neuronal Death ◽  
Α Subunit ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Field

In the central nervous system, interleukin (IL)-3 has been shown to exert a trophic action only on septal cholinergic neurons in vitro and in vivo, but a widespread distribution of IL-3 receptor (IL-3R) in the brain does not conform to such a selective central action of the ligand. Moreover, the mechanism(s) underlying the neurotrophic action of IL-3 has not been elucidated, although an erythroleukemic cell line is known to enter apoptosis after IL-3 starvation possibly due to a rapid decrease in Bcl-2 expression. This in vivo study focused on whether IL-3 rescued noncholinergic hippocampal neurons from lethal ischemic damage by modulating the expression of Bcl-xL, a Bcl-2 family protein produced in the mature brain. 7-d IL-3 infusion into the lateral ventricle of gerbils with transient forebrain ischemia prevented significantly hippocampal CA1 neuron death and ischemia-induced learning disability. TUNEL (terminal deoxynucleotidyltransferase–mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling) staining revealed that IL-3 infusion caused a significant reduction in the number of CA1 neurons exhibiting DNA fragmentation 7 d after ischemia. The neuroprotective action of IL-3 appeared to be mediated by a postischemic transient upregulation of the IL-3R α subunit in the hippocampal CA1 field where IL-3Rα was barely detectable under normal conditions. In situ hybridization histochemistry and immunoblot analysis demonstrated that Bcl-xL mRNA expression, even though upregulated transiently in CA1 pyramidal neurons after ischemia, did not lead to the production of Bcl-xL protein in ischemic gerbils infused with vehicle. However, IL-3 infusion prevented the decrease in Bcl-xL protein expression in the CA1 field of ischemic gerbils. Subsequent in vitro experiments showed that IL-3 induced the expression of Bcl-xL mRNA and protein in cultured neurons with IL-3Rα and attenuated neuronal damage caused by a free radical–producing agent FeSO4. These findings suggest that IL-3 prevents delayed neuronal death in the hippocampal CA1 field through a receptor-mediated expression of Bcl-xL protein, which is known to facilitate neuron survival. Since IL-3Rα in the hippocampal CA1 region, even though upregulated in response to ischemic insult, is much less intensely expressed than that in the CA3 region tolerant to ischemia, the paucity of IL-3R interacting with the ligand may account for the vulnerability of CA1 neurons to ischemia.

Sign in / Sign up

Export Citation Format

Share Document