[A study of the neuroprotective effect of mexidol on the cell model of glutamate stress]. / Izuchenie neiroprotektivnogo deistviia meksidola nakletochnoi modeli glutamatnogo stressa.

AIM: To study a neuroprotective effect of mexidol on the cell model of glutamate stress. MATERIAL AND METHODS: Cytological studies of an effect of glutamate stress on cerebellar granule cells were carried out. RESULTS: Mexidol increased neuronal survival after the addition of glutamate by 8-10% (p<0.05). The effect of mexidol was more pronounced at the stage of neuron culture growth (5 days), cell survivability increased on average by 20%. CONCLUSION: The results of the study confirmed the neuroprotective effect of mexidol in the neuronal culture in glutamate toxicity model.

[Pharmacokinetic and pharmacodynamic synergism between neuropeptides and lithium in the neurotrophic and neuroprotective action of cerebrolysin].

OBJECTIVE: To study the synergism between neuropeptides and lithium ions. MATERIAL AND METHODS: An experimental model of stroke (chronic bilateral occlusion of the common carotid arteries in rats), neuronal culture studies, histomorphological analyses, determination of micronutrient profile of brain substrates were used. RESULTS: A complex of experimental studies revealed that the effect of cerebrolysin is influenced by the synergism between lithium ions and the neuropeptide contentof this drug. Pharmacokinetic synergism promotes the accumulation of lithium in brain tissues during cerebrolysin treatment. The existence of the pharmacokinetic synergism is evident from the potentiation of neuroprotective effects of the drug under the action of lithium ions established in the model of stroke. CONCLUSION: Lithium ions potentiate neuroprotective effects of cerebrolysin.

The lack of extracellular Na+ exacerbates Ca2+-dependent damage of cultured cerebellar granule cells.

Rhodamine 123 staining, light and electron microscopy were used to evaluate the ultrastructural and functional state of cultured cerebellar granule cells after short treatment with the solution where NaCl was substituted by sucrose (sucrose balance salt medium, SBSM). Cell exposure to SBSM for 20 min resulted in the fact that mitochondria in the neurons lost their ability to sequester rhodamine 123. This effect could be prevented by: (i) non-competitive N-methyl-D-aspartate (NMDA) receptor channel blocker, 10(-5) M MK-801; (ii) a competitive specific antagonist of NMDA glutamate receptors, 0.25 x 10(-3) M D,L-2-amino-7-phosphonoheptanoate (APH); (iii) 10(-3) M cobalt chloride; (iv) removal of Ca2+ from the medium. Low Na+ in the Ca2+-containing medium caused considerable mitochondrial swelling in granule cells. However, the same treatment in the absence of calcium ions in the medium abolished the deleterious effect of SBSM on the neuronal mitochondrial structure and functions. It is suggested that (i) the exposure of cultured cerebellar granule cells to SBSM leads to a release of endogenous glutamate from cells; (ii) Ca2+ ions potentially de-energizing neuronal mitochondria enter the neuron preferentially through the NMDA channels rather than through the Na+/Ca2+ exchanger; (iii) mitochondrial swelling in granule cells is highly Ca2+-dependent; (iv) cellular overload with sodium ions can activate mitochondrial Na+/Ca2+ exchanger and thus prevent permeability transition pore opening in mitochondria.