ABSTRACT
OBJECTIVE: Investigation of the neuroprotective properties of lithium ascorbate on the stress models in vivo and in vitro. MATERIAL AND METHODS: Neurocytological and behavioral studies on nerve cell culture and animal stress models. RESULTS: Significant neuroprotective effect of lithium ascorbate in neuronal cultures exposed to glutamate toxicity and adaptogenic effect of this drug in stress model in rats were shown. CONCLUSION: The results suggest lithium ascorbate has a high neuroprotective potential in stress models in vivo and in vitro.
Subject(s)
Adaptation, Physiological/drug effects , Lithium Compounds/therapeutic use , Neuroprotective Agents/therapeutic use , Stress, Psychological/drug therapy , Animals , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Cells, Cultured , Disease Models, Animal , Glutamic Acid/pharmacology , Lithium Compounds/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Rats , Rats, WistarABSTRACT
Using the model of bilateral photothrombosis of the blood vessels in the prefrontal cortex we have shown that new hybrid proteins derived from recombinant human erythropoietin, carbamylated EPO-Fc and EPO-TR fusion proteins, injected intraperitoneally 1 h after ischemic injury contribute to restoration of passive avoidance response formed before photothrombotic injury and reduction in the volume of the ischemic focus. These data attest to nootropic and neuroprotective activities of these hybrid proteins. Carbamylated glycopeptide derivative ÐPO-TR exhibited prolonged neuroprotective properties.
Subject(s)
Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Erythropoietin/chemistry , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Animals , Humans , Male , Neuroprotective Agents/therapeutic use , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Rats , Stroke/drug therapyABSTRACT
Neuroprotective and antiamnesic effects of human nerve growth factor (HNGF) synthetic dipeptide mimetic bis-(N-monosuccinyl-glycyl-lysine)hexamethylenediamide (GK-2h) has been studied on a model of bilateral photochemically induced focal ischemical brain injury in prefrontal cortex of rats. It is established that a single intraperitoneal injection of GK-2h (0.1 mg/kg) 1 h or 4 h after operation, followed by injections on the 2nd, 4th and 8th days after operation, results (on the 9th day) in reduction of the cortical infarction volume by 47 or 65%, and leads to restoration of the passive avoidance reflex (acquired before experimental ischemic insult) by 42 and 60%, respectively. It is concluded that GK-2h possesses significant neuroprotective properties.
Subject(s)
Brain Ischemia/drug therapy , Dipeptides/pharmacology , Nerve Growth Factor/pharmacology , Neuroprotective Agents/pharmacology , Peptidomimetics/pharmacology , Stroke/drug therapy , Animals , Avoidance Learning/drug effects , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Dipeptides/chemistry , Humans , Male , Nerve Growth Factor/chemistry , Neuroprotective Agents/chemistry , Peptidomimetics/chemistry , Prefrontal Cortex/pathology , Prefrontal Cortex/physiopathology , Rats , Stroke/pathology , Stroke/physiopathologyABSTRACT
The neuroprotective activity of recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been observed in rats with model intracerebral post-traumatic hematoma (hemorrhagic stroke). It is established that rhEPO-loaded PLGA nanoparticles produce a neuroprotective effect in rats with hemorrhagic stroke, which is manifested by reduced number of lethal outcomes and animals with neurological disorders. Treatment with rhEPO-loaded PLGA prevented amnesia of passive avoidance reflex (PAR), which was produced by the hemorrhagic stroke, and reduced the area of brain damage caused by the intracerebral hematoma. These effects were recorded during one-week observation period. Native rhEPO exhibited a similar, but much less pronounced effect on the major disorders caused by the model hemorrhagic stroke in rats.
Subject(s)
Amnesia/prevention & control , Cerebral Hemorrhage, Traumatic/drug therapy , Erythropoietin/therapeutic use , Neuroprotective Agents/therapeutic use , Animals , Avoidance Learning/drug effects , Cerebral Hemorrhage, Traumatic/mortality , Cerebral Hemorrhage, Traumatic/physiopathology , Disease Models, Animal , Drug Carriers/chemistry , Erythropoietin/administration & dosage , Humans , Lactic Acid/chemistry , Male , Nanoparticles/chemistry , Neuroprotective Agents/administration & dosage , Particle Size , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Survival RateABSTRACT
The effect of the new original drug celleks on the functional CNS activity and volume of ischemic damage has been studied in the experimental model of photochemically induced bilateral thrombosis of the prefrontal cortex. The chronic (once a day during 4 days) and even single (one hour after the operation) treatment of rats with celleks (intraperitoneal, 3 mg/kg) after the cortical photothrombosis resulted in the restoration of passive avoidance and diminishing of the volume of ischemic damage.
Subject(s)
Brain Ischemia/drug therapy , Nerve Growth Factors/therapeutic use , Neuroprotective Agents/therapeutic use , Prefrontal Cortex/drug effects , Animals , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Conditioning, Classical/drug effects , Disease Models, Animal , Drug Administration Schedule , Injections, Intraperitoneal , Male , Nerve Growth Factors/administration & dosage , Neuroprotective Agents/administration & dosage , Prefrontal Cortex/pathology , Prefrontal Cortex/physiopathology , Rats , Treatment OutcomeABSTRACT
Data on intracellular processes induced by a low glucose level in nerve tissue are presented. The involvement of glutamate and adenosine receptors, mitochondria, reactive oxygen species (ROS), and calcium ions in the development of hypoglycemia-induced damage of neurons is considered. Hypoglycemia-induced calcium overload of neuronal mitochondria is suggested to be responsible for the increased ROS production by mitochondria.
Subject(s)
Brain/metabolism , Hypoglycemia/metabolism , Neurons/metabolism , Animals , Brain/pathology , Calcium/metabolism , Glutamates/metabolism , Humans , Hypoglycemia/physiopathology , Mitochondria/metabolism , Models, Biological , Neurons/pathology , Reactive Oxygen Species/metabolismABSTRACT
Current data on glutamate-induced functional and morphological changes in mitochondria correlating with or being a result of their membrane potential changes are reviewed. The important role of Ca2+, Na+, and H+ in the potentiation of such changes is considered. It is assumed that glutamate-induced loss of mitochondrial potential is mediated by Ca2+ overload resulting in the induction of nonspecific permeability of the inner mitochondrial membrane.
Subject(s)
Excitatory Amino Acids/physiology , Glutamic Acid/toxicity , Mitochondria/drug effects , Calcium/metabolism , Cytoplasm/metabolism , Homeostasis , Membrane Potentials/drug effects , Mitochondria/metabolism , Mitochondria/ultrastructure , Neurons/drug effects , Neurons/metabolism , Permeability , Receptors, Glutamate/drug effects , Receptors, Glutamate/metabolismABSTRACT
Treatment of cultured rat cerebellar granular cells with calmodulin antagonist bifonazole (10 mM) during oxygen-glucose deprivation or exposure to glutamate (75 mM) prevented neuronal death. However, addition of bifonazole after glutamate treatment promoted neuronal death. Calmodulin antagonists trifluoperazine and thioridazine had no protective effects, while thioridazine even potentiated the toxic effect of glutamate.
Subject(s)
Antifungal Agents/pharmacology , Cerebellum/drug effects , Glucose/pharmacology , Glutamic Acid/metabolism , Imidazoles/pharmacology , Oxygen/pharmacology , Animals , Calcium/metabolism , Calmodulin/antagonists & inhibitors , Cell Death , Cells, Cultured , Cerebellum/cytology , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Glucose/metabolism , Glutamates/pharmacology , Oxygen/metabolism , Rats , Rats, Wistar , Thioridazine/pharmacology , Time Factors , Trifluoperazine/pharmacologySubject(s)
Cerebellum/cytology , Mitochondria/physiology , Neurons/physiology , Sodium/deficiency , 2-Amino-5-phosphonovalerate/analogs & derivatives , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Calcium/pharmacology , Cells, Cultured , Cerebellum/ultrastructure , Cobalt/pharmacology , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Membrane Potentials , Mitochondria/drug effects , Neurons/drug effects , Neurons/ultrastructure , Osmosis , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Solutions , Sucrose/pharmacologyABSTRACT
Argon anoxia and glucose deprivation were used for modeling of ischemic damage in the cultures of cerebellar granule cells. Protective effect of peptide piracetam analogue GVS-111 was demonstrated. GVS-111 prevented neurodegeneration induced by glutamate and oxidative stress. In contrast to GVS-111, piracetam did not attenuate neurocytotoxic effect of glutamate.
