[Neurotransmission mechanism of movement disorders in multiple sclerosis].

A significant elevation of blood levels of exciting amino acids aspartate and glutamate as well as taurine was found. There was a strong association between the levels of these mediator amino acids and neurological deficit severity, progressive course of the disease and predominant damage of supraspinal and spinal descending motor systems. The data obtained suggest an important role of excitotoxicity in the mechanisms of autoimmune demyelinisation and development of progressive neurodegenerative changes. The results of the study emphasize the significance of neurotransmitters in development of motor functions, first of all spastic paresis. In this connection, the normalization of functional activity of neurotransmitter systems involved in the nerve tissue damage and responsible, along with immunomodulation and activation of remyelination, for motor behavior is considered as an important approach to multiple sclerosis treatment and reduction of disability caused by the disease progression.

[A relationship between clinical and biological disturbances in atherosclerotic lesions of the carotid arteries].

A study of the functional state of cerebral hemodynamics using transcranial dopplerography and blood excitotoxic amino acids, playing an important role in the pathogenesis of ischemic brain damage, has been carried out in 43 patients with atherosclerotic lesions of the carotid arteries. Neurological deficit that developed as a result of ischemic stroke was related to the changes of cerebral hemodynamics (a decrease of hemodynamic reserve and blood flow velocity in the middle cerebral artery) and an increase of the level of blood amino acids involved in excitotoxic mechanisms of the nerve tissue lesions in brain ischemia. These biochemical disturbances in the non-acute period of ischemic stroke may be explained by the state of chronic excitotoxicity that developed because of blood circulation insufficiency in the brain and a decrease of cerebrovascular reserve. The authors admit that genetically determined features of cerebral metabolism of excitotoxic amino acids, concomitant with their higher release to the extracellular space, along with hemodynamical disturbances, may be risk factors of ischemic brain lesion when cerebral blood flow decreased as a result of stenosis or occlusion of the carotid arteries. This should be taken into account for elaboration of complex methods of neuroprotection in atherosclerosis of the great brain arteries.

[Mechanisms of lability of neurological symptoms in multiple sclerosis]. / Mekhanizmy labil'nosti nevrologicheskikh simptomov pri rasseiannom skleroze.

Pathophysiological peculiarities of demyelinated axons determine their high sensitivity to different exogenous factors and are the reason of instability of neurological signs in MS. One of the typical MS sing is high sensitivity to elevated temperature of the body. Even temporary elevation in body temperature may cause changes in impulse conduction in demyelinated fibres, which was proved by studies of evoked potentials and stabilometric studies. These disturbances may be associated with disorder of ions channels function. The role of other factors (metabolic and immunological disturbances, levels of cytokines and neurotransmitters) in temporary block of nerve conduction in MS is discussed. Further studies of the mechanisms of the lability of neurological sings in MS may lead to elaboration of new approaches to MS treatment.

[Physiopathological and chemopathological mechanisms of central motor disorders in amyotrophic lateral sclerosis]. / Patofiziologicheskie i patokhimicheskie mekhanizmy tsentral'nykh dvigatel'nykh narushenii pri bokovom amiotroficheskom skleroze.

A complex study of pathophysiological characteristics of corticospinal systems was performed in patients with amyotrophic sclerosis (ALS) by transcranial magnetic resonance stimulation (TMRS) and estimation of the levels of mediatory amino acids in the cerebrospinal fluid (CSF). There was a time course of changes in the excitability of cortical motor neurons (MNs) and in the functional status of the pyramidal tract as ALS progressed. The large cortical MNs were found to be afflicted just at early stages by further involving their axonal systems into the pathological process. As a result, mainly fine slowly conducting axons of MNs functioned at the later stages of the disease. Neurochemical changes correlated with the duration of the disease and were supposed to play an important role in the pathogenesis of ALS. Besides, a significant correlation revealed by TMRS between the pathology of the corticospinal tract and the cerebrospinal fluid levels of glutamate confirmed the role of glutamate as a the main neurotransmitter of this motor system. The results of the study also confirm the significance of excitotoxic mechanisms in central motor disorders in ALS.

Changes in neurotransmitters in multiple sclerosis.

Patients with multiple sclerosis were found to have increased cerebrospinal fluid, noradrenaline, and excitatory amino acid (glutamate and aspartate) levels, with increased blood glutamine, asparagine, and glycine levels. An association was found between these biochemical parameters and the nature and severity of neurological symptoms, as well as with the course of the disease. Neurotransmitters are proposed to have a role in the pathogenesis of multiple sclerosis, particularly in the biochemical mechanisms of the relationship between the nervous and immune systems, as well as in the neurochemical mechanisms underlying the development of neurological deficit.

[The changes of lipids, lipoproteins and apolipoproteins in plasma in ischemic stroke]. / Izmenenie soderzhaniia lipidov, lipoproteinov i apolipoproteinov v plazme krovi pri ishemicheskom insul'te.

Contents of lipids (cholesterol CS, triglycerides) as well as levels of CS of lipoproteins of different density and of apolipoproteins A1 and B were measured in blood serum of 31 patients in different periods after of ischemic stroke. The majority of the indices studied were significantly decreased in men in acute periods of the stroke, especially in 8-21 days after the stroke development. Meanwhile, the levels of lipids, CS lipoproteins of both low and very low densities were increased later. Contents of CS of antiatherogenic lipoproteins of high density (HDLP) was low in different periods after the development of disorders of cerebral circulation. This confirms the concept that low level of HDLP is one of the risk factors of ischemic stroke. Decrease of the levels of both lipids and CS of lipoproteins of different density was more pronounced in patients with more severe atherosclerotic damages of the main cerebral arteries. Disorders of metabolism of lipoproteins in ischemic disorders of cerebral circulation are discussed with reference to literary data taking into consideration their heterogeneity. Genetically determined pathology of certain apolipoproteins plays a key role factor in the development of early atherosclerosis and in the elucidation of biochemical markers of the primary damages of cerebral vessels.

[Neurotransmitter changes in multiple sclerosis]. / Izmeneniia neirotransmitterov pri rasseiannom skleroze.

Elevated levels of norepinephrine and of excitatory amino acids (glutamate, aspartate) were observed in cerebrospinal fluid of patients with multiple sclerosis while there were elevated content of glutamine, asparagine and glycine in their blood. An important point concerning these results was the relation between biochemical indices and the character of neurological symptoms, their severity as well as the course of the disease. The role of neurotransmitters in pathogenesis of multiple sclerosis and particularly in biochemical mechanisms of the relation between nervous and immune system that underlie the development of neurological deficiencies is suggested.

[Neurotransmitter changes in amyotrophic lateral sclerosis]. / Izmeneniia neirotransmitterov pri bokovom amiotroficheskom skleroze.

The results of investigation concerning both total and cerebral catecholamine metabolism indices in 78 patients with amyotrophic lateral sclerosis (ALS) are presented. The considerable elevation of both blood and liquor norepinephrine level as well as of blood epinephrine concentration was observed together with acute decrease of platelet MAO B activity. The conclusion was made about the participation of catecholamines in exitotoxic mechanisms of motor neurons systems death which was quite characteristic for ALS development. A short literary review was presented concerning the role of neurotransmitters in regulation of motor functions. The neurochemical disturbances which may result in release of exitotoxic mechanisms of ALS were considered too. The consideration of data obtained as well as the analysis of modern conceptions of ALS pathogenesis enable both to determine some ways of ALS pathogenetic therapy and to define the basic directions of further investigations.

[The pathology of catecholamine metabolism in cerebrovascular diseases]. / K patologii metabolizma katekholaminov pri tserebrovaskuliarnykh zabolevaniikh.

Blood catecholamines were investigated with high-performance liquid chromatography and electrochemical detection in 95 patients with cerebrovascular affections. On day 1-3 since ischemic apoplexy blood norepinephrine and dopamine levels increased significantly. This is possibly due to their active release from neurons in brain tissue ischemia. High blood catecholamines are thought an unfavourable factor aggravating the disease and responsible for cardiac sequelae. Ways of cerebral tissue protection in case of ischemia are suggested.

[Pathological status of catecholamines in the corpus striatum in hepatocerebral dystrophy (Wilson-Konovalov disease)]. / K patologii katekholaminov v polosatom tele pri gepatotserebral'noi distrofii (bolezni Vil'sona-Konovalova).

The content of catecholamines in the striatum was measured in 2 patients suffering from hepatocerebral dystrophy (Wilson-Konovalov disease). It is noted that in different clinical manifestations of the disease, the changes in the content of noradrenaline in the striatum varied. A male patient with marked tremor spreading manifested a considerable rise of the content of catecholamines, primarily in the n. caudatus. At the same time in a female patient with a grave akinetic -rigid syndrome and the signs of liver failure, the content of catecholamines, particularly dopamine, in the putamen was low. In view of this fact it is assumed that disorders of cerebral metabolism of catecholamines, dopamine in particular, evidently related to deposition of excess copper, leading to the changes of their content in basal ganglia underline the clinical pleomorphism of the disease and play the key role in the development of extrapyramidal motor disturbances characteristic of hepatocerebral dystrophy.

[Catecholamine metabolism in extrapyramidal disorders in patients with chronic hypertensive encephalopathy]. / Metabolizm katekholaminov pri ékstrapiramidnykh narusheniiakh u bol'nykh s khronicheskoi gipertonicheskoi éntsefalopatiei.

Total and cerebral metabolism of catecholamines (CA) was examined in patients with associated chronic hypertonic encephalopathy and extrapyramidal disorders. It was discovered for the first time that there was an increase in noradrenaline in the blood and cerebrospinal fluid together with a lowering of the content of dopamine and major metabolite thereof along the pathway of oxidative deamination of homovanillic acid. CA metabolism was shown to correlate with the patients' age, duration and gravity of extrapyramidal disorders. It is suggested that the revealed metabolic disorders of CA--neurotransmitters which are likely to underlie the development of neurological deficiency and characteristic mental disorders occur as a result of the diverse complex of biochemical alterations and are related both to the complex mechanisms of the pathogenesis of essential hypertension and ischemic injury to the brain as well as to the localization in the brain of lacunar infarctions. The complexity of the pathogenic treatment of the disease is emphasized. The main approaches to the pharmacological correction of the revealed disorders are outlined.

[Catecholamine metabolism in essential tremor]. / Metabolizm katekholaminov pri éssentsial'nom tremore.

The pathogenesis of essential tremor (ET) is evidently very complicated and involves various biochemical and pathophysiological mechanisms. The pathology of cerebral adrenergic systems is attributed a high value in the development of the disease. The general catecholamine (CA) metabolic indices were investigated in 40 ET patients. CA excretion was considerably decreased, especially that of norepinephrine, while the urinary level of a CA precursor DOPA was essentially normal. The excretion of a major epinephrine and norepinephrine metabolite vanillylmandelic acid also tended to decrease. Contrarily to the CA excretion, their blood levels did not change considerably. The data are supposed to point to a reduction of the general CA body pool, especially of norepinephrine. This yields the shift of relationship between lepinephrine and norepinephrine toward the latter, that can provide another mechanism for ET. Possible deterioration of noradrenergic neurotransmission as a pathogenic factor of ET, and adrenergic receptors hypersensitivity in particular, are still pending. Major genetically predetermined biochemical defect in ET leading to impaired control of complicated mechanisms behind the regulation of synchroneous activity of spinal motor structures, is believed to be closely related to CA systems modifying ET in response to various impacts and involving the mechanisms of central action alcohol.

[Characteristics of biochemical, electrophysiological and morphological changes in experimental cerebral ischemia]. / Osobennosti biokhimicheskikh, élektrofiziologicheskikh i morfologicheskikh izmenenii pri éksperimenta'lnoi ishemii mozga.

The results of experiments performed in Wistar rats are indicative of the catecholamine release during the first hours of developing cerebral ischemia, and their role in activation of lipid peroxidation (LP). These events were characteristically enhanced in the ischemic hemisphere where EEG changes were most pronounced. Maximal changes in slow parieto-occipital EEG waves amplitude and malonic dialdehyde levels in the brain tissue were also correlated. This metabolic-electrophysiological link than could be of major importance for EEG monitoring of brain pathochemistry and pathology needs, however, further investigation. Among pathological findings, the relationship between the degree of ischemic neuronal changes on one hand, and brain swelling and hyperemia on the another, was worth attention. The lack in distinct correlations between metabolic, electrophysiological and structural changes in the ischemic brain can be accounted for by a substantial spread of ischemic damage over the brain.

[Role of catecholamines in the pathogenesis of extrapyramidal hyperkinesis]. / Znachenie katekholaminov v patogeneze ékstrapiramidnykh giperkinezov.

The total and cerebral metabolism of catecholamines was studied in 134 patients with various extrapyramidal hyperkinetic syndromes. Homovanillic acid levels determined in the ventricular and lumbar cerebrospinal fluid served as an indicator of the cerebral metabolism of dopamine. In two patients with hepatocerebral dystrophy (HCD) and torsion dystonia the author studied the content of catecholamines in the cerebral tissue. This study showed a considerable increase in noradrenalin and dopamine levels in the striatum, which was more pronounced in cases of HCD. It has been concluded on the basis of the findings obtained that elevation of cerebral dopaminergic activity is one of characteristic biochemical signs of extrapyramidal hyperkineses. There was a significant increase in this activity following the destruction of the ventrolateral nucleus of the thalamus, which appears to be one of the biochemical mechanisms underlying an unfavourable effect of stereotaxic surgery for extrapyramidal hyperkineses. The importance of this pathology of noradrenergic systems in the pathogenesis of extrapyramidal diseases remains unclear and needs further investigation.