Frontiers in stroke · 2026
Beneficial effects of the novel first-in-class compound DX243 on ischemic outcomes following in vitro and in vivo models of stroke.
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Marlier Quentin, Boreux Alexia, Rives Arnaud, Mosca Dario, Michaux Helene, Schmitz Louisa, Attali Pierre, Silvente Stéphane, Lefebvre Philippe, Malgrange Brigitte, Caron Nicolas
Аннотация
INTRODUCTION: New therapeutic strategies to mitigate the devastating consequences of stroke are urgently needed, as restoration of blood flow is currently the only and limited available treatment.
METHODS: In our study, we employed a comprehensive combination of in vitro and in vivo stroke models to investigate the therapeutic potential of the DX243. Specifically, we used glutamate and oxygen-glucose deprivation/reoxygenation (OGD) treatment models to mimic ischemic conditions in vitro. To transpose these data in vivo, we used the middle cerebral artery occlusion (MCAO) model to induce an ischemic stroke in male C57BL/6J mice.
RESULTS: Our results demonstrated that DX243 significantly increased ATP production following glutamate treatment and neuronal viability following OGD.Forty-eight hours after 1 h of MCAO, mice that received one subcutaneous injection of DX243 presented a reduced infarct volume and preserved motor coordination on the rotarod, while effects on open field locomotion were not statistically significant.
CONCLUSION: These results highlight the promising neurorestorative properties of this new molecule and suggest its potential as a therapeutic agent for stroke patients. Further investigations in preclinical and clinical settings are warranted to elucidate its full therapeutic potential.
METHODS: In our study, we employed a comprehensive combination of in vitro and in vivo stroke models to investigate the therapeutic potential of the DX243. Specifically, we used glutamate and oxygen-glucose deprivation/reoxygenation (OGD) treatment models to mimic ischemic conditions in vitro. To transpose these data in vivo, we used the middle cerebral artery occlusion (MCAO) model to induce an ischemic stroke in male C57BL/6J mice.
RESULTS: Our results demonstrated that DX243 significantly increased ATP production following glutamate treatment and neuronal viability following OGD.Forty-eight hours after 1 h of MCAO, mice that received one subcutaneous injection of DX243 presented a reduced infarct volume and preserved motor coordination on the rotarod, while effects on open field locomotion were not statistically significant.
CONCLUSION: These results highlight the promising neurorestorative properties of this new molecule and suggest its potential as a therapeutic agent for stroke patients. Further investigations in preclinical and clinical settings are warranted to elucidate its full therapeutic potential.