Use of Succinates for Correction of Metabolic Impairments in the Ischemic Penumbra Zone in Stroke Patients

Abstract

Vascular brain diseases resulting from acute ischemia or chronic hypoxia are a serious problem in current healthcare provision. Thus, there has been no decrease in the incidence of ischemic stroke. Gradually progressing chronic cerebral ischemia is also associated with increased disability. The sequelae of acute cerebral ischemia in the form of pareses and paralyses or those of chronic ischemia in the form of intellectual-memory impairments and dementia lead to the imposition of financial and moral costs on the working population. There is a good evidence base for several current approaches to the treatment of stroke patients, used either in the first hours of the development of cerebral catastrophe -thrombolytic therapy -or treatment associated with the prophylaxis of stroke. Another potential direction in the treatment of stroke consists of antioxidant protection of the brain in the most acute period of stroke, which requires grounding in evidence using contemporary methods of paraclinical monitoring, particularly neuroimaging.The use of antioxidants and antihypoxic agents in patients with vascular brain diseases has attracted focused attention over recent decades. The biochemical and pathophysiological grounds for the use of these agents are well known. Hypoxia accompanies many diseases which in turn are risk factors for cerebrovascular pathology. In a number of cases, hypoxia initiates whole cascades of pathophysiological reactions which elicit direct damage to brain tissue. Thus, when the content of peroxide compounds is excesThe aim of the present work was to use MR spectroscopy to assess the quantitative contents and ratios of different metabolites in the infarct nucleus, ischemic penumbra, and unaltered tissue in the opposite hemisphere in patients in the acute period of ischemic stroke. A total of 72 patients were studied, of whom 37 (the study group) received the antioxidant Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) in addition to basal treatment, while 35 patients received only standard treatment without use of antioxidants. Stroke severity was assessed on the NIHSS scale and functional outcomes on day 30 were evaluated using the Bartel index and modified Rankin scale. MR proton spectroscopy was performed twice: during the first 24 h of disease onset and on day 5. Use of the succinate-containing antioxidant Mexidol (500 mg i.v. for 14 days) during the acute period of ischemic stroke significantly decreased the intracellular lactate (p = 0.002) and inositol contents (p = 0.005) from the levels in the control group, which helped restore the balance between the aerobic and anaerobic mechanisms of oxidation and had favorable influences on the rehabilitation potentials of the patients. A positive correlation was found between the lactate content in the ischemic penumbra zone and values on the NIHSS (r = 0.5786, p = 0.049), along with a negative correlation between the lactate content in the ischemic penumbra zone and the level of functional recovery assessed on the Bartel index (r = -0.6305, p ...

The role of somatic factors in early childhood and adolescent psychosomatic disorders

“…After birth, the child's nervous system must meet and deal directly with all environmental signals. 26 Thus, the onset of extrauterine development starts with a stress shock, which can serve as a basis for future pathologies. In subsequent periods of a child's psychological development, the body is exposed to adverse environmental factors.…”

Mitochondrial dysfunctions and antihypoxants

“…Mexidol is used mainly for secondary MD in neurodegenerative diseases, acute and chronic cerebrovascular accidents, traumatic brain injury, heart failure [1,44,73]. However, despite the experimental and clinical advantages of mexidol over other succinate-containing drugs, ethylmethylhydroxypyridine succinate is not included in the international guidelines for the treatment of cerebrovascular accidents due to methodological reasons (small patient samples in clinical trials, the inclusion and exclusion criteria, etc.)…”