RT Journal Article
T1 Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke.
A1 Martínez-Alonso, Emma
A1 Escobar-Peso, Alejandro
A1 Ayuso, Maria I
A1 Gonzalo-Gobernado, Rafael
A1 Chioua, Mourad
A1 Montoya, Juan J
A1 Montaner, Joan
A1 Fernández, Israel
A1 Marco-Contelles, José
A1 Alcázar, Alberto
K1 antioxidant
K1 brain ischemia
K1 hydroxyl radical
K1 ischemic stroke
K1 neuroprotection
K1 nitrones
K1 reactive oxygen species
K1 steroids
AB Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.
SN 2076-3921
YR 2020
FD 2020-03-31
LK https://hdl.handle.net/10668/26800
UL https://hdl.handle.net/10668/26800
LA en
DS RISalud
RD Apr 17, 2025