The role of oxidative stress in acute experimental hemorrhagic stroke and therapeutic effects of Mexidol

Authors:
VORONINA T.A., KRAYNEVA V.A., ZOLOTOV N.N., KOTELNIKOVA S.O., VALDMAN E.A.

FGBNU "Research Institute of Pharmacology named after V.V. Zakusova ”, Moscow, Russia

Place of publication:
S.S. KORSAKOV JOURNAL OF NEUROLOGY AND PSYCHIATRY, 2022, Vol. 122, No. 8, Issue 2

Abstract:
Objective of the study. To study the role of oxidative stress in the development of disorders occurring in hemorrhagic stroke (HS) and to evaluate the effect of Mexidol on neurological and cognitive impairment in HS with an analysis of the relationship between the therapeutic effects of the drug and its antioxidant action. Material and methods. The study was conducted on sexually mature outbred male rats weighing 260-280 g. The HS model was created by destroying brain tissue in the capsula interna area with the introduction of blood into the damaged area. On days 1, 7 and 14 after the HS modeling, death, neurological deficit (McGrow scale, rotarod test, RRT), seizures, and cognitive impairment were recorded in rats. In parallel, a quantitative analysis of oxidative stress parameters was performed with an assessment of TBA-active (thiobarbituric acid - TBA) products in the blood plasma and homogenates of the cerebral cortex of rats. Mexidol was administered intraperitoneally at a dose of 150 mg/kg during the first 3 days after surgery, then orally (from the 4th to the 14th day) at a dose of 75 mg/kg. Results. In rats with HI, Mexidol significantly increases survival, reduces the severity of neurological deficit according to the McGrow scale (circle movements, paresis of 1-4 limbs, paralysis of the lower limbs, lateral position), eliminates seizures, restores motor coordination disorder (MCD), and improves learning and memory processes. Mexidol normalizes the concentrations of TBA-active products in the blood of animals and in rat cerebral cortex homogenates 1 and 7 days after HI. Conclusion. The obtained data indicate the role of oxidative stress in the development of disorders in HI and the ability of Mexidol to attenuate neurological deficit, seizure manifestations, and cognitive impairment in HI, which limits the manifestations of oxidative stress. All of this substantiates the importance of Mexidol in patients with hemorrhagic stroke and determines the specific features of its therapeutic effects. Key words: hemorrhagic stroke, intracerebral hematoma, oxidative stress, Mexidol, neurological deficit, seizures, cognitive impairment.