Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition

D’aes, Tine; Marlier, Quentin; Verteneuil, Sébastien; Quatresooz, Pascale; Vandenbosch, Renaud; Malgrange, Brigitte

doi:10.3390/ijms24087009

Open AccessArticle

Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition

by

Tine D’aes

¹,

Quentin Marlier

^1,2,

Sébastien Verteneuil

^1,3,

Pascale Quatresooz

³,

Renaud Vandenbosch

^1,3,† and

Brigitte Malgrange

^1,*,†

¹

Laboratory of Developmental Neurobiology, GIGA-Stem Cells & GIGA-Neurosciences, University of Liège, 4000 Liège, Belgium

²

Dendrogenix, Avenue de l’Hôpital, 1—B34 +3, 4000 Liège, Belgium

³

Division of Histology, Department of Biomedical and Preclinical Sciences, University of Liège, 4000 Liège, Belgium

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(8), 7009; https://doi.org/10.3390/ijms24087009

Submission received: 16 March 2023 / Revised: 3 April 2023 / Accepted: 6 April 2023 / Published: 10 April 2023

(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Acute Stroke 2.0)

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Abstract

Previous research has shown that cyclin-dependent kinases (Cdks) that play physiological roles in cell cycle regulation become activated in post-mitotic neurons after ischemic stroke, resulting in apoptotic neuronal death. In this article, we report our results using the widely used oxygen–glucose deprivation (OGD) in vitro model of ischemic stroke on primary mouse cortical neurons to investigate whether Cdk7, as part of the Cdk-activating kinase (CAK) complex that activates cell cycle Cdks, might be a regulator of ischemic neuronal death and may potentially constitute a therapeutic target for neuroprotection. We found no evidence of neuroprotection with either pharmacological or genetic invalidation of Cdk7. Despite the well-established idea that apoptosis contributes to cell death in the ischemic penumbra, we also found no evidence of apoptosis in the OGD model. This could explain the absence of neuroprotection following Cdk7 invalidation in this model. Neurons exposed to OGD seem predisposed to die in an NMDA receptor-dependent manner that could not be prevented further downstream. Given the direct exposure of neurons to anoxia or severe hypoxia, it is questionable how relevant OGD is for modeling the ischemic penumbra. Due to remaining uncertainties about cell death after OGD, caution is warranted when using this in vitro model to identify new stroke therapies.

Keywords: neurons; cell culture; OGD; cortex; mouse; cell culture

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MDPI and ACS Style

D’aes, T.; Marlier, Q.; Verteneuil, S.; Quatresooz, P.; Vandenbosch, R.; Malgrange, B. Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition. Int. J. Mol. Sci. 2023, 24, 7009. https://doi.org/10.3390/ijms24087009

AMA Style

D’aes T, Marlier Q, Verteneuil S, Quatresooz P, Vandenbosch R, Malgrange B. Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition. International Journal of Molecular Sciences. 2023; 24(8):7009. https://doi.org/10.3390/ijms24087009

Chicago/Turabian Style

D’aes, Tine, Quentin Marlier, Sébastien Verteneuil, Pascale Quatresooz, Renaud Vandenbosch, and Brigitte Malgrange. 2023. "Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition" International Journal of Molecular Sciences 24, no. 8: 7009. https://doi.org/10.3390/ijms24087009

APA Style

D’aes, T., Marlier, Q., Verteneuil, S., Quatresooz, P., Vandenbosch, R., & Malgrange, B. (2023). Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition. International Journal of Molecular Sciences, 24(8), 7009. https://doi.org/10.3390/ijms24087009

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Re-Evaluating the Relevance of the Oxygen–Glucose Deprivation Model in Ischemic Stroke: The Example of Cdk Inhibition

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