Neuroprotective action of Cortexin, Cerebrolysin and Actovegin in acute or chronic brain ischemia in rats

Autor: Maksim V. Shmidt, A. V. Smirnov, E. I. Morkovin, E.E. Abrosimova, D. V. Kurkin, Igor E. Makarenko, Artem Dorotenko, Dmitry V. Verkholyak, Ivan N. Tyurenkov, Nikolay S. Kovalev, Anna V. Kalatanova, D. A. Bakulin, Marina A. Dubrovina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Morris water navigation task
Pharmacology
Brain Ischemia
Brain ischemia
chemistry.chemical_compound
Mice
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Brain Damage
Amino Acids
Materials
Neurons
Cerebral Ischemia
Multidisciplinary
Pharmaceutics
Drugs
Neuroprotective Agents
Neurology
Cerebrolysin
Physical Sciences
Medicine
Intercellular Signaling Peptides and Proteins
medicine.symptom
Cellular Types
Research Article
Drug Administration
Science
Materials Science
Ischemia
Brain damage
Heme
Neuroprotection
Rotarod performance test
03 medical and health sciences
Necrosis
Signs and Symptoms
Drug Therapy
In vivo
Adhesives
medicine
Animals
business.industry
Biology and Life Sciences
Cell Biology
medicine.disease
Rats
030104 developmental biology
chemistry
Cellular Neuroscience
Clinical Medicine
business
Neuroprotectives
030217 neurology & neurosurgery
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 7, p e0254493 (2021)
ISSN: 1932-6203
Popis: This study was the first to compare the neuroprotective activity of Cerebrolysin®, Actovegin® and Cortexin® in rodent models of acute and chronic brain ischemia. The neuroprotective action was evaluated in animals with acute (middle cerebral artery occlusion) or chronic (common carotid artery stenosis) brain ischemia models in male rats. Cortexin® (1 or 3 mg/kg/day), Cerebrolysin® (538 or 1614 mg/kg/day) and Actovegin® (200 mg/kg/day) were administered for 10 days. To assess the neurological and motor impairments, open field test, adhesive removal test, rotarod performance test and Morris water maze test were performed. Brain damage was assessed macro- and microscopically, and antioxidant system activity was measured in brain homogenates. In separate experiments in vitro binding of Cortexin® to a wide panel of receptors was assessed, and blood-brain barrier permeability of Cortexin® was assessed in mice in vivo. Cortexin® or Cerebrolysin® and, to a lesser extent, Actovegin® improved the recovery of neurological functions, reduced the severity of sensorimotor and cognitive impairments in rats. Cortexin® reduced the size of necrosis of brain tissue in acute ischemia, improved functioning of the antioxidant system and prevented the development of severe neurodegenerative changes in chronic ischemia model. Radioactively labeled Cortexin® crossed the blood-brain barrier in mice in vivo with concentrations equal to 6–8% of concentrations found in whole blood. During in vitro binding assay Cortexin® (10 μg/ml) demonstrated high or moderate binding to AMPA-receptors (80.1%), kainate receptors (73.5%), mGluR1 (49.0%), GABAA1 (44.0%) and mGluR5 (39.7%), which means that effects observed in vivo could be related on the glutamatergic and GABAergic actions of Cortexin®. Thus, Cortexin, 1 or 3 mg/kg, or Cerebrolysin®, 538 or 1614 mg/kg, were effective in models acute and chronic brain ischemia in rats. Cortexin® contains compounds acting on AMPA, kainate, mGluR1, GABAA1 and mGluR5 receptors in vitro, and readily crosses the blood-brain barrier in mice.
Databáze: OpenAIRE
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