[Brain benzodiazepine receptors in humans and rats with alcohol addiction].

OBJECTIVE: Benzodiazepine receptors (BDR) in synaptosomal and mitochondrial membranes from different brain areas of alcohol abused patients (postmortem) and the brain cortex of male rats (Vistar line) with different preference to alcohol were studied. METHODS: Synaptosomal and mitochondrial receptors of membranes from different brain areas of patients with alcohol addiction and controls were explored using radioreceptor analysis with selective ligands [3H]flunitrazepam and [3H]PK-11195. BDR in the rat brain were studied using [3H]flunitrazepam and [3H]Ro5-4864. RESULTS: An analysis of kinetic parameters (Kd and Bmax) of [3H]flunitrazepam and [3H]PK-11195 binding with synaptosomal and mitochondrial membranes in the human brain showed that BDR was decreased and capacity increased in different human brain areas under the influence of alcohol abuse. The most distinct changes were found in the prefrontal cortex, nucleus caudatus and cerebella cortex. Alcohol abuse induced greater changes in mitochondrial membranes compared to synaptosomal membranes that was consistent with physiological and defensive functions of mitochondrial membranes and CNS under the influence of toxic substances. The affinity of [3H]flunitrazepam and [3H]Ro5-4864 binding with membranes was decreased, but the capacity of receptors was increased in the brain cortex of alcohol-preferring male rats compared to alcohol non-preferring rats. Administration of anticonvulsant meta-chloro-benzhydryl-urea to rats prefer ethanol increased the affinity of BDR.

Effect of meta-chlorobenzhydryl urea (m-ClBHU) on benzodiazepine receptor system in rat brain during experimental alcoholism.

Chronic alcohol intake induces neuroadaptive changes in benzodiazepine receptors modulating GABAA receptors that promote alcohol addiction. Analysis of benzodiazepine receptors in the brain of Wistar rats differing by alcohol preference has demonstrated that affinity of [(3)H]flunitrazepam and [(3)H]Ro5-4864 binding with membrane fraction was reduced, while the density of specific binding sites in the brain cortex of heavy drinking and low drinking rats was increased in comparison with rats nonpreferring alcohol. Administration of anticonvulsant meta-chlorobenzhydryl urea increased affinity of benzodiazepine receptors in the brain cortex of heavy drinking rats, which improved GABA neurotransmission in the brain of these animals and reduced alcohol consumption.

[Synaptogenesis and formation of benzodiazepine receptors in the human brain in conditions of prenatal alcoholization].

The aim was to study correlations between the development of synaptic connections and benzodiazepine receptors functionally linked to the brain GABA system in the brain of embryos and 8-15 week fetuses obtained from women with alcoholism. Material from 33 women with alcoholism, stage II (ICD-10 F10.201 and F10.202), and 30 healthy people (controls) was studied. The retardation in the formation of synaptic benzodiazepine receptors and increase in their density was seen in brain cells developing in conditions of prenatal alcoholization compared to controls. The authors consider these findings as a manifestation of compensatory reactions directed towards the adaptation of the fetal nervous system to the action of alcohol and as functional insufficiency of the brain GABA system.

Development of brain vessels in human embryos and fetuses in conditions of prenatal exposure to alcohol.

Light and electron microscopy were used to study the characteristics of the formation of brain vascular structures at the early stages of development in conditions of maternal alcoholization during pregnancy. Computer morphometric methods using the Scion Image system for image analysis showed that fetuses at 11-12 weeks of development in conditions of prenatal alcohol exposure showed a decrease in the mean absolute cross-sectional area of vessels in the intermediate layer of the brain, with an increase in their relative area and an increase per unit area of sections, as compared with the control group. Vessels started to differentiate into arteries and veins from 10 weeks of development.

[Development of brain vessels in human embryos and fetuses subjected to prenatal exposure to alcohol].

Using light and electron microscopy, the peculiarities of the formation of brain blood vessel structure were studied at the early stages of brain development in human embryos and fetuses, whose mothers took alcohol during the period of pregnancy. Computer morphometric methods with the application of Scion Image program of image analysis demonstrated that in fetuses subjected to prenatal alcohol exposure, at weeks 11 and 12 of development, the average absolute sectional area of blood vessels in the intermediate layer of the brain was diminished, while blood vessel relative area and number per unit area of section were increased as compared to similar values in control group. The process of differentiation of blood vessels into arterial and venous ones was shown to start since developmental week 10.

[Efficacy of cytoflavin in spondylogenic radiculomyeloischemia]. / Effektivnost' tsitoflavina pri spondilogennykh radikulomieloishemiiakh.

The efficacy of cytoflavin in the treatment of 60 patients (39 women, 21 men, age 32-64 year) with spondylogenic cervical and lumbosacral radiculomyeloischemia due to degenerative dystrophic spinal lesions was studied in a randomized double-blind placebo controlled study according to GCP rules. During 10 days 40 patients received intravenous cytoflavin dropper injections once daily; 20 patients (control group) received 5% glucose solution as a placebo. Considerable improvement was observed in 70% patients with radiculomyeloischemia of cervical localization and in 65%--with radiculomyeloischemia of lumbosacral segments. In the control group, positive dynamics of neurologic symptoms was 25-30% lower. Cytoflavin significantly reduced cognitive disturbances, improved reparative processes both in the central and peripheral neurons, and may be recommended in ischemic neuronal spinal lesions.

[The dynamics of developmental disorders of the brain in fetuses obtained from mothers consuming alcohol during pregnancy (14- to 15-week-old fetuses)]. / Dinamika narushenii razvitiia golovnogo mozga plodov, poluchennykh ot materei, upotrebliavshikh alkogol' v period beremennosti (plody 14--15 ned).

By histological method cerebral development was studied in 3 fetus obtained after 14, 14 and 15 weeks to gestation in the mothers abusing alcohol. The excessive plication, invagination and adhesions of the brain wall, porencephalia, abnormal hyperplasia and heterotopia of cells, as well as agenesis of plexus choroideus were detected. These finding were compared with the disturbances in 5- to 12-week-old embryos which had been earlier discovered by authors. It was noted their resemblance, which means the stability of the structural brain changes during ontogenesis.

[Dysontogenesis of the brain of the progeny born to mothers drinking alcohol during pregnancy]. / Dizontogenez golovnogo mozga potomstva materei, upotrebliavshikh alkogol' v period beremennosti.

A study was made of the development of the brain from 44 embryos (5-12 weeks) and 1 fetus (14 weeks) obtained from mothers who used alcohol during pregnancy. 16 cases made up the control group. In 34 cases out of 45 (75.5%), deviations in the development of the brain were established and distributed into the three degrees of gravity: mild, moderate and severe. 11 variants of brain pathology are described. Deviations in the formation of brain walls and disorders of the development of the cortical lamina occurred most frequently (70.6 and 57.9%, respectively). In alcoholic mothers, brain pathology in their progeny was revealed in 100% of cases. Provided they used alcohol systematically and frequently, brain pathology was identified in 83.3% of cases, in systematic rare use of alcohol in 77.3%, and in episodic use of alcohol in 28.5% of cases.

[Development of embryonal brain synapses in the normal state and in maternal alcoholism]. / Formirovanie sinapsov émbrional'nogo golovnogo mozga v norme i pri alkogolizme materi.

Electron microscopy was used to study embryonal brains (n-10) of 7-12-week gestation from mothers abusing alcohol at the time of medical abortion. Control group consisted of 20 embryos from healthy women. The study group demonstrated delayed formation of synaptic structures, a great number of extrasynaptic contacts, sings of clear-type degeneration of some mature synapses.

[Ultrastructural characteristics of embryonic brain cells in the offspring of alcoholic mothers]. / Osobennosti u'ltrastruktury kletok émbriona'lnogo golovnogo mozga pri alkogolizme materi.

Electron microscopy of brain cells was performed in 20 human embryos at 10 to 12 weeks of gestation. Of these, 13 were delivered at medical abortions from healthy women, and 7 from women with 2nd stage alcoholism. In both groups the electron-dense structures were shown in the perinuclear space of neuro- and glioblasts. In embryos taken from alcoholic mothers, these cells displayed the changes in plasma and mitochondrial membranes structure with appearing inclusions and enhanced development of several organels. The data on ultrastructural changes in alcoholic brain embryonic cells are compared to those in other maternal mental disorders.

[Disorders of brain development in embryos obtained from mothers who abused alcohol]. / Narusheniia razvitiia golovnogo mozga émbrionov, poluchennykh ot zloupotrebliavshikh alkogolem materei.

Nineteen 5 to 12-weeks-old embryos from women abusing alcohol during pregnancy (alcoholism, habitual drinking) were studied. In 15 (79%) the brain development disorders were detected. Most frequently concerned were the brain hemispheres. Defective development signs were also noted in the midbrain, choroidal plexus and diencephalon. Microdysplasias were found in different brain regions. In one case embryonal signs of the capsula interna, nucleus caudatus, putamen, epiphysis cerebri, habenular nuclei, chiasma, optical tracts were absent. Six groups presenting most typical deviations were identified. The degree of embryonal brain disorders correlated with its mother's alcohol abuse severity.

[Acetylcholinesterase activity in the brains of rats in a model of alcoholic embryopathy]. / Aktivnost' atsetilkholinésterazy v mozge krys v usloviiakh modelirovaniia alkogol'noi émbriopatii.

Acetylcholinesterase (ACE) activity was studied by the Karnovsky-Ruts method from the 5th to the 30th day in the brain of young rats born to chronically alcoholized animals receiving ethanol for 3 to 5 months prior to conception as well as during pregnancy and breast feeding. Alcohol was found to induce deviations in the formation of the enzyme in the adjacents nucleus and Broca's diagonal strip on days 5 and 20 of the postnatal development, respectively. It is assumed that the above deviations are involved in manifestations of the alcoholic syndrome of the fetus.