Edaravone Improves Intermittent Hypoxia-Induced Cognitive Impairment and Hippocampal Damage in Rats

Abstract

Oxidative stress plays an essential role in obstructive sleep apnea-hypopnea syndrome-induced cognitive dysfunction in children. This study investigated the effects of edaravone, a potent free radical scavenger, on intermittent hypoxia (IH)-induced oxidative damage and cognition impairment in a young rat model of IH. IH rats were treated with edaravone for 4 weeks. Behavioral testing was performed using the Morris water maze, and hippocampal tissues were harvested for further analyses. Edaravone attenuated IH-induced cognitive impairment, reduced morphological and structural abnormalities, and increased the number of mitochondria in the IH rats. Furthermore, edaravone significantly increased the inhibition of hydroxyl free radicals; reduced expressions of superoxide anion, malondialdehyde, and 8-hydroxy-2′-deoxyguanosine; and upregulated the expression of manganese superoxide dismutase, catalase, cAMP, protein kinase A, phosphorylated-cAMP response element-binding (p-CREB), B-cell lymphoma 2, and brain-derived neurotrophic factor in the hippocampal tissue of IH rats. Our findings suggest that edaravone attenuated IH-induced cognitive impairment and hippocampal damage by upregulating p-CREB in young rats.

Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study

“…Among the drugs used in the present study, edaravone was the most efficient in treating the hypoxia-related effects. Indeed, after using this drug, we observed a significant attenuation of hypoxia and oxygen–glucose deprivation effects, demonstrated by a significant increase in cell viability and by a decrease in ROS production, corroborating previous studies showing the efficacy of this drug in hypoxia in vitro [ 28 , 39 ] as well as in vivo models [ 40 , 41 , 42 ]. We believe that these results support the effects of edaravone on hippocampal HT-22 cells under hypoxic conditions, showing that this drug is very efficient in attenuating the impact of hypoxia in hippocampal cells.…”

Effects of the Edaravone, a Drug Approved for the Treatment of Amyotrophic Lateral Sclerosis, on Mitochondrial Function and Neuroprotection

“…Intermittent hypoxia-induced rats showed decreased antioxidant enzyme levels and increased apoptotic signaling from mitochondria, leading to impaired cognition and hippocampal function. Edaravone treatment reversed these impairments in intermittent hypoxia-induced rats [ 78 ]. Edaravone was also found to restore expression of PINK1/Parkin and mitochondrial dynamics-related proteins in cerebral ischemia-reperfusion in rats with middle cerebral artery occlusion.…”

Edaravone mitigates cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome via regulation of cAMP/PKACREB pathway

“…Activation of cAMP/PKA pathway led to increased mitochondrial activity, thereby reducing the release of ROS, indicating that edaravone not only eliminated ROS through single electron transfer, but also increased the ROS clearance intensity through activation of this pathway [17][18][19][20]. It is known that BDNF is a downstream molecule of phosphorylated CREB gene transcription, and its levels are highest in CNS, hippocampus and cortex.…”