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This research was funded by the Spanish Ministry of Science, Innovation and Universities Ref RTI2018-095793-B-I00 and Comunidad Autonoma de Madrid Ref. B2017/BMD-3827 to MGL. ETN PURINESDX Research and Innovation Agreement N degrees 766124. Program under the Marie Sklodowska-Curie and Proyectos Santander-Universidad Autonoma de Madrid 2017, to MFCA.

Analysis of institutional authors

Lopez, Manuela GAuthorCano-Abad MfCorresponding Author

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

Publicated to:Cells. 9 (3): - 2020-03-01 9(3), DOI: 10.3390/cells9030664

Authors: Garrosa J, Paredes I, Marambaud P, López MG, Cano-Abad MF

Affiliations

Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain. - Author
Hosp Univ la Princesa, Inst Invest Biomed, Diego Leon 62, Madrid 28006, Spain - Author
Instituto de Investigaciones Biomédicas del Hospital Universitario de la Princesa, Diego de León 62, 28006 Madrid, Spain. - Author
Instituto Teofilo Hernando, Facultad de Medicina, Universidad Autonoma de Madrid, 28029 Madrid, Spain. - Author
Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY 11030 USA - Author
The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA. - Author
Univ Autonoma Madrid, Fac Med, Dept Farmacol, Madrid 28029, Spain - Author
Univ Autonoma Madrid, Fac Med, Inst Teofilo Hernando, Madrid 28029, Spain - Author
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Abstract

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.

Keywords

Benzothiazepine cgp37157CalciumCalhm1Cgp37157Ion-channelIschemiaIschemic-strokeNeuroprotection

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cells due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.24, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-15, the following number of citations:

  • WoS: 9
  • Scopus: 9
  • Europe PMC: 6
  • Google Scholar: 12
  • OpenCitations: 11

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-15:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/693480

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Garrosa J) and Last Author (CANO ABAD, MARIA FRANCISCA).

the author responsible for correspondence tasks has been CANO ABAD, MARIA FRANCISCA.