Optimization of choline administration regimen for correction of cognitive functions in rats after brain injury.

Choline diet promotes improvement of the brain cognitive functions in rats with moderate-to-severe traumatic brain injury. In previous studies, the rats received choline being standard (0.2%) or choline-supplemented (2%) diet for 2 weeks prior to and 2 weeks after experimental brain injury. To the end of the experiments (in 4 weeks), the post-traumatic disturbances in the cognitive functions were observed in both groups, although they were less pronounced than in the rats kept on the choline-supplemented diet. Based on original mathematical model, this paper proposes a method to calculate the most efficient use of choline to correct the brain cognitive functions. In addition to evaluating the cognitive functions, the study assessed expression of α7 nicotinic acetylcholine receptors, the amount of consumed food and water, and the dynamics of body weight.

Dynamics of the response to variations in dietary choline content in rats.

A mathematical model was developed based on the analysis of body response to variations in choline content in the ration of growing rats. The peculiarities of choline metabolism and the expression of α7-nicotinic receptors in the brain were studied. The information obtained can be useful for comparative analysis of choline administration for correction of certain cerebral pathologies.

An autoradiographic analysis of rat brain nicotinic receptor plasticity following dietary choline modification.

Choline is known to be involved with numerous physiological functions of the nervous system and also acts as a direct acting agonist of alpha7 nicotinic acetylcholine receptors (nAChRs). The purpose of this study was to conduct a brain region-specific evaluation of changes in nAChR subtype expression following dietary choline modification. In addition, we assessed changes in body weight, food/water intake, as well as changes in spatial learning (Morris Water Maze) in response to dietary choline modification. Male Sprague-Dawley rats were exposed to standard, choline supplemented or choline deficient diets for periods of 14 or 28 days. Choline supplemented animals gained significantly less weight over the course of the experiment, in spite of the fact that there were minimal differences in food consumption between the dietary regimens. Spatial memory did not differ between animals maintained on a standard rat diet, and the choline supplemented food. Brains of the animals kept on the diets for 14 and 28 days were used for quantitative autoradiographic analysis of nicotinic receptor subtypes using 125I-Bungarotoxin (alpha7) and 125I-Epibatidine (non-alpha7). There were no significant differences in nicotinic receptor binding or physiologic parameters measured between animals fed standard and choline deficient diets. However 2 weeks of dietary choline supplementation caused significant up-regulation of alpha7 receptors without significant effect on the density of non-alpha7 nAChRs. Increases in BTX binding predominantly occurred in cortical and hippocampal brain regions and ranged between 14 and 30% depending on the brain region. The results of our study suggest that choline acts as a selective agonist at alpha7 nicotinic cholinergic receptors in the rat central nervous system.

Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease.

Despite the well-known adverse health effects of tobacco smoking, numerous studies have shown that nicotine, the principal pharmacologically active alkaloid in tobacco smoke, exerts neuroprotective properties in several animal models of neurodegeneration. Furthermore, cigarette smoking appears to significantly reduce the risk of developing Parkinson's disease in human subjects. We review the animal and human studies that investigated possible neuroprotective actions of nicotine and other nicotinic receptor agonists and antagonists. We demonstrate that nicotine is not neuroprotective in all animal models of neurodegenerative disease. In fact, C57Bl/6 mice pretreated with nicotine have an increased sensitivity to 3-nitropropionic acid, a neurotoxin used in mice to mimic some aspects of Huntington's disease. The actions of nicotine on dopamine release may explain the variable effects of nicotine in animal models of Parkinson's and Huntington's diseases. Finally, we focus on some future directions for studies that evaluate neuroprotective properties of nicotinic agonists and antagonists.

[The formation of a test system for assessing the safety of different types of pertussis preparations: their cytotoxic action on mouse thymocytes in vitro]. / K formirovaniiu sistemy testov otsenki bezopasnosti kokliushnykh preparatov razlichnogo tipa: tsitotoksicheskoe deistvie na timotsity myshei in vitro.

The test for the evaluation of the toxicity of different types of pertussis preparations as manifested by their in vitro influence on mouse thymic cells (T test) has been finally worked out. The use of the T test has made it possible to reveal the nonstandard character of the production lots of adsorbed diphtheria-pertussis-tetanus vaccines, both whole-cell vaccine and Japanese acellular vaccine. The degree of the in vitro damaging action of pertussis preparations on mouse thymic cells greatly depends on the residual content of Bordetella pertussis nontoxoidized toxin which, in contrast to B. pertussis lipopolysaccharide and filamentous hemagglutinin, produces pronounced cytotoxic action on mouse thymic cells.