scholarly journals Molecular and Pharmacological Modulation of CALHM1 Promote Neuroprotection against Oxygen and Glucose Deprivation in a Model of Hippocampal Slices

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 664 ◽  
Author(s):  
Javier Garrosa ◽  
Iñigo Paredes ◽  
Philippe Marambaud ◽  
Manuela G. López ◽  
María F. Cano-Abad
Keyword(s):  
Neuroprotective Effect ◽  
Hippocampal Slices ◽  
Glucose Deprivation ◽  
Point Of View ◽  
Oxygen And Glucose Deprivation ◽  
Molecular Events ◽  
Vitro Model ◽  
Species Production ◽  
Reperfusion Phase

Calcium homeostasis modulator 1 (CALHM1) is a calcium channel involved in the regulation of cytosolic Ca2+ levels. From a physiological point of view, the open state of CALHM1 depends not only on voltage but also on the extracellular concentration of calcium ([Ca2+]) ions. At low [Ca2+]e or depolarization, the channel is opened, allowing Ca2+ influx; however, high extracellular [Ca2+]e or hyperpolarization promote its resting state. The unique Ca2+ permeation of CALHM1 relates to the molecular events that take place in brain ischemia, such as depolarization and extracellular changes in [Ca2+]e, particularly during the reperfusion phase after the ischemic insult. In this study, we attempted to understand its role in an in vitro model of ischemia, namely oxygen and glucose deprivation, followed by reoxygenation (OGD/Reox). To this end, hippocampal slices from wild-type Calhm1+/+, Calhm1+/−, and Calhm1−/− mice were subjected to OGD/Reox. Our results point out to a neuroprotective effect when CALHM1 is partially or totally absent. Pharmacological manipulation of CALHM1 with CGP37157 reduced cell death in Calhm1+/+ slices but not in that of Calhm1−/− mice after exposure to the OGD/Reox protocol. This ionic protection was also verified by measuring reactive oxygen species production upon OGD/Reox in Calhm1+/+ and Calhm1−/− mice, resulting in a downregulation of ROS production in Calhm1−/− hippocampal slices and increased expression of HIF-1α. Taken together, we can conclude that genetic or pharmacological inhibition of CALHM1 results in a neuroprotective effect against ischemia, due to an attenuation of the neuronal calcium overload and downregulation of oxygen reactive species production.

Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid

2006 ◽  
Vol 24 (4) ◽  
pp. 285-291 ◽  
Author(s):  
Bárbara Tagliari ◽  
Lauren L. Zamin ◽  
Christianne G. Salbego ◽  
Carlos Alexandre Netto ◽  
Angela T.S. Wyse
Keyword(s):  
Folic Acid ◽  
In Vitro Model ◽  
Brain Slices ◽  
Glucose Deprivation ◽  
Oxygen And Glucose Deprivation ◽  
Vitro Model

scholarly journals Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

2020 ◽  
Vol 21 (23) ◽  
pp. 8921
Author(s):  
Jonas Ort ◽  
Benedikt Kremer ◽  
Linda Grüßer ◽  
Romy Blaumeiser-Debarry ◽  
Hans Clusmann ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Cell Damage ◽  
Neuroprotective Effect ◽  
Hippocampal Slices ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Modern Medicine ◽  
Technical Note

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.

scholarly journals L-α-Aminoadipate Reduces Glutamate Release from Brain Tissue Exposed to Combined Oxygen and Glucose Deprivation

1997 ◽  
Vol 17 (5) ◽  
pp. 567-570 ◽  
Author(s):  
Tor S. Haugstad ◽  
Iver A. Langmoen
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Glucose Deprivation ◽  
Gaba Release ◽  
Dependent Manner ◽  
Oxygen And Glucose Deprivation ◽  
Energy Deprivation ◽  
Dose Dependent ◽  
The Brain

The effect of the glutamate analogue L- α-aminoadipate ( αAA) on the release of glutamate and γ-aminobutyric acid (GABA) from rat hippocampal slices was investigated in vitro. Oxygen/glucose deprivation caused a large release of glutamate and GABA. αAA added during energy deprivation reduced the glutamate release in a dose-dependent manner (56% reduction at 5 m M), whereas GABA release was unchanged. We speculate that ischemic glutamate release from the brain is mediated by a low affinity transport mechanism that is blocked by αAA.

Size Does Matter: Generation of Intrinsic Network Rhythms in Thick Mouse Hippocampal Slices

2005 ◽  
Vol 93 (4) ◽  
pp. 2302-2317 ◽  
Author(s):  
Chiping Wu ◽  
Wah Ping Luk ◽  
Jesse Gillis ◽  
Frances Skinner ◽  
Liang Zhang
Keyword(s):  
In Vitro Model ◽  
Adult Mouse ◽  
Hippocampal Slices ◽  
Network Connectivity ◽  
Slice Preparation ◽  
Fundamental Properties ◽  
Mouse Hippocampus ◽  
Hippocampal Network ◽  
Vitro Model

Rodent hippocampal slices of ≤0.5 mm thickness have been widely used as a convenient in vitro model since the 1970s. However, spontaneous population rhythmic activities do not consistently occur in this preparation due to limited network connectivity. To overcome this limitation, we develop a novel slice preparation of 1 mm thickness from adult mouse hippocampus by separating dentate gyrus from CA3/CA1 areas but preserving dentate–CA3-CA1 connectivity. While superfused in vitro at 32 or 37°C, the thick slice exhibits robust spontaneous network rhythms of 1–4 Hz that originate from the CA3 area. Via assessing tissue O2, K+, pH, synaptic, and single-cell activities of superfused thick slices, we verify that these spontaneous rhythms are not a consequence of hypoxia and nonspecific experimental artifacts. We suggest that the thick slice contains a unitary circuitry sufficient to generate intrinsic hippocampal network rhythms and this preparation is suitable for exploring the fundamental properties and plasticity of a functionally defined hippocampal “lamella” in vitro.

Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis

2016 ◽  
Vol 340 (1) ◽  
pp. 150-158 ◽  
Author(s):  
Roberta Bonafede ◽  
Ilaria Scambi ◽  
Daniele Peroni ◽  
Valentina Potrich ◽  
Federico Boschi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stromal Cells ◽  
In Vitro Model ◽  
Neuroprotective Effect ◽  
Adipose Derived Stromal Cells ◽  
Vitro Model ◽  
Lateral Sclerosis

scholarly journals The Anti-Apoptotic Effect of ASC-Exosomes in an In Vitro ALS Model and Their Proteomic Analysis

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1087 ◽  
Author(s):  
Bonafede ◽  
Brandi ◽  
Manfredi ◽  
Scambi ◽  
Schiaffino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Beneficial Effect ◽  
Proteomic Analysis ◽  
In Vitro Model ◽  
Neuroprotective Effect ◽  
Protein Profile ◽  
Cell Based Therapy ◽  
Apoptotic Effect ◽  
Vitro Model

Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 α, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases.

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