Cortexin Research & Studies

Biomarkers such as Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor κ-B (RANK), its ligand RANKL, and Transient Receptor Potential Canonical 1 (TRPC1) have been implicated in the neuroprotective response to neuronal injury, with their expression potentially influenced by antioxidant treatments. The objective of this study was to investigate the effects of Cortexin on the expression of these biomarkers in brain tissue following cerebral ischemia-reperfusion (I/R) injury.

To evaluate the efficacy, safety, and dose-dependent effects of Cortexin in the comprehensive therapy of alcoholic encephalopathy (EA).

Study of the therapeutic equivalence of forms for intramuscular and intravenous administration of the drug Cortexin in patients in the acute and early recovery periods of ischemic stroke (IS).

To evaluate the effectiveness of complex rehabilitation measures using the drug Cortexin in children with neuropsychiatric pathology during a one-year follow-up.

The aim of this study was to investigate whether Cortexin®, a brain peptide-containing agent, has any mitigating effect on high glucose-induced neuropathy, using primary cultured rat sensory neurons.

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.

To study the possibility of using the polypeptide drug cortexin for the treatment of cognitive, emotional and behavioral disorders in children and adolescents with epilepsy and to assess the efficacy and safety of the drug in this group of patients.

To study an effect of cortexin on neurological symptoms and oxidative stress as part of the ischemic cascade in chronic cerebral ischemia (CCI), I-II stages.

The aim of this report is to evaluate whether cortexin provides any protective activity against ototoxicity of cisplatin.

The goal of treatment of brain pathologies may be regarded as re-establishment of optimal brain plasticity. Disturbances in neuroplasticity are associated with the appearance of multiple targets that should be subjects for pharmacological correction. Peptide hydrolysates derived from animal brain became a basis for multi-component organ-specific drugs which are widely used for treatment of cerebral pathologies. Potentially, the presence of many components in such drugs may be beneficial for simultaneous effects on different targets. In this article, new data are analyzed related to relevant molecular mechanisms underlying neuroprotective properties of cortexin. On a model of accelerated aging in rats, cortexin restored the ratio of pro- and antioxidative systems and demonstrated a significant anti-inflammatory effect both in the brain and at the systemic level. In in vitro experiments cortexin effectively and tissue-specifically inhibited brain caspase-8. Neuron-specific proteins β5-tubulin, creatine kinase B and protein 14-3-3 α/β were shown to be molecular partners of cortexin peptides in the brain. Thus, potential molecular mechanisms of cortexin neuroprotective effects are various and associated with key processes underlying neuroplasticity: signal transduction, energy metabolism, proteolytic protein modification, cell structure, as well as neuroinflammation. The pleiotropicity of mechanisms of cortexin action is based on the composition of the drug containing a variety of neuropeptides. The tissue specificity of these mechanisms determines to a significant degree the efficacy of the drug in treatment of cerebral pathologies.

Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent.

To study the efficacy and tolerability of cortexin in the treatment of cognitive dysfunction in children.

Cortexin, a drug containing hydrolyzed brain peptides, has long been used in clinics, but the mechanisms of its action remain obscure. We have hypothesized that cortexin-related neuroprotection is associated with the ability of the drug to inhibit brain proteases. Cortexin effectively inhibited brain caspase-8, while its effects on caspase-1, -3, -9, cathepsin B and calpain were much less pronounced or absent. In addition, we isolated a peptide fraction from cortexin holding all the inhibitory capacity of the original drug, but with a much more simple composition. Both cortexin and its fraction prevented neuronal damage in a culture model of glutamate-induced cell death. Neuroprotective effect of Cortexin may be mediated by inhibition of the initiator caspase-8 in the brain.

To study the effectiveness and sustained effects of early appointment of a repeated course of low-dose drug cortexin neuroprotection in patients in acute and recovery period of hemispheric ischemic stroke.

The aim was to investigate the efficacy of cortexin and methylprednisolone on recovery in cases of traumatic facial nerve paralysis occurring after facial nerve trauma.

Neurotrophic drug cortexin, a lyophilized extraction of animal cortex, comprises neuropeptides, amino acids and trace elements. The nucleoprotein complexes of the cerebral cortex can also retain elements of chromatin with DNA fragments. All of these components of cortexin have a specific range of "targets" for the specific correction of the molecular and cellular processes at various stages of the pathological process. A modern concept of neurosignaling considers the associated processes - from the synaptic level to the epigenetic patterns of neuron nucleus, in which an important place belongs to corrective peptide molecules. Peptide components of cortexin derived from the animal brain, which interact with cellular and molecular "targets", provide a new view on mechanisms of neuroprotection.

The authors present the review of works devoted to one of peptide bioregulators (the biologically active agent) known as cortexin, which is used in memory and attention recovery. The cerebral cortex drug cortexin was created in Military Medical Academy in 1986. The cortexin favourable effect on cerebral mnestic and cognitive functions in different patient groups was noted. The possible mechanisms involved in recovery of these higher nervous activity functions are discussed.

Nucleotide sequence analysis of a cDNA clone of a rat cortex-enriched mRNA identifies a novel integral membrane protein of 82 amino acids. The encoded protein is named cortexin to reflect its enriched expression in cortex. The amino acid sequence of rat cortexin and its mouse homologue are nearly identical (98% similarity), and both contain a conserved single membrane-spanning region in the middle of each sequence. Northern blot analysis shows that cortexin mRNA is brain-specific, cortex-enriched, and present at significant levels in fetal brain, with peak expression in postnatal rodent brain. In situ hybridization studies detect cortexin mRNA primarily in neurons of rodent cerebral cortex, but not in cells of the hindbrain or white matter regions. The function of cortexin may be particularly important to neurons of both the developing and adult cerebral cortex.