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

Abstract

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.

Identification of a glycolysis- and lactate-related gene signature for predicting prognosis, immune microenvironment, and drug candidates in colon adenocarcinoma

“…Inhibition of the Wnt/beta-catenin signaling pathway and epithelial-mesenchymal transition by CLCA1 can reduce CRC aggressiveness ( Li et al, 2017 ). In a chronic ischemia model, CTXN reduced the size of necrosis of brain tissue, improved the functioning of the antioxidant system and reduced neurodegenerative changes ( Kurkin et al, 2021 ). In CRC, FLNA induces epithelial-mesenchymal transition, which activates the smad2 pathway, increasing chemoresistance ( Cheng et al, 2020 ).…”

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program

“…Determination of the Prevalence of Postcovid Syndrome sion of leukocytes to the endothelium and their migration across the endothelium, decreases proinfl ammatory cytokine expression, and increases the density of the blood:brain barrier (BBB), which reduces its permeability [17]. Cytoskeletal proteins, interacting with Cortexin (actin, 14-3-3-α/β protein), form tight junctions in the vascular endothelium, promoting maintenance of BBB integrity, which is extremely important in conditions of viral infection [18]. The drug, acting on GABA receptors and ionotropic metabotropic glutamate receptors, prevents excitotoxicity and promotes optimization of excitation and inhibition processes, which is clinically important for patients with chronic cerebral ischemia (CCI) and cephalgic and vestibuloatactic syndromes [18].…”

“…Cytoskeletal proteins, interacting with Cortexin (actin, 14-3-3-α/β protein), form tight junctions in the vascular endothelium, promoting maintenance of BBB integrity, which is extremely important in conditions of viral infection [18]. The drug, acting on GABA receptors and ionotropic metabotropic glutamate receptors, prevents excitotoxicity and promotes optimization of excitation and inhibition processes, which is clinically important for patients with chronic cerebral ischemia (CCI) and cephalgic and vestibuloatactic syndromes [18]. All four identifi ed brain proteins interacting with Cortexin (tubulin β5, creatine kinase BB, 14-3-3-α/β protein, and actin) support the maturation and insertion of young neurons into neural networks, regulate enzyme activity, protect against protein dephosphorylation, and drive sequestration and neuroprotection processes in neurodegenerative diseases [18].…”

“…The drug, acting on GABA receptors and ionotropic metabotropic glutamate receptors, prevents excitotoxicity and promotes optimization of excitation and inhibition processes, which is clinically important for patients with chronic cerebral ischemia (CCI) and cephalgic and vestibuloatactic syndromes [18]. All four identifi ed brain proteins interacting with Cortexin (tubulin β5, creatine kinase BB, 14-3-3-α/β protein, and actin) support the maturation and insertion of young neurons into neural networks, regulate enzyme activity, protect against protein dephosphorylation, and drive sequestration and neuroprotection processes in neurodegenerative diseases [18]. The main mechanisms of these processes are based on changes in the expression of genes regulating the synthesis of neurotrophic factors BDNF and NGF [19].…”

“…The following results were obtained: treatment was followed in both groups by two-fold decreases in olfactory impairments (p < 0.001). Use of neurotrophic factors can probably "spare" degenerating neurons and stimulate axon and dendrite growth and form new connections after viral infection [18,24,25].…”