Bilobalide prevents ischemia-induced edema formation in vitro and in vivo.

EGb761, a standardized extract of Ginkgo biloba, has neuroprotective properties in animal models of ischemia, an activity that is partially attributed to its constituent, bilobalide. EGb761 has also been reported to inhibit edema formation induced by toxins such as triethyltin. The goal of this study was to test the activity of pure bilobalide to prevent edema formation in models of ischemia. Oxygen-glucose deprivation (OGD) in rat hippocampal slices served as a model of in vitro-ischemia. OGD caused cellular edema formation as indicated by an increase of slice water contents in 30 min. Bilobalide (1-10 microM) reduced slice water contents in ischemic slices in a concentration-dependent manner. As a model of in vivo-ischemia, we performed middle cerebral artery occlusion (MCAO) in mice. Permanent MCAO caused cell death and swelling of the ischemic hemisphere within 24 h. Pretreatment of the mice with bilobalide (10 mg/kg i.p.) reduced infarct area by 43% (as judged by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining) and edema formation by 70% (as judged by hemispheric enlargement). In parallel experiments, pretreatment with bilobalide also reduced forebrain water contents in the ischemic hemisphere by 57%. As an alternative model of brain edema formation, we used water intoxication to increase brain water content; bilobalide, was, however, inactive in this model. We conclude that bilobalide strongly and specifically attenuates edema formation in models of brain ischemia in vitro and in vivo. Bilobalide may be therapeutically effective in brain edema which occurs secondarily to large hemispheric stroke and traumatic brain injury in humans.

Neurogenesis in adolescent brain is potently inhibited by ethanol.

Adolescence is a period of progressive changes in brain that likely contribute to the maturation of behavior. Human adolescents consume large amounts of ethanol. To investigate the effects of ethanol on adolescent neural progenitor cells, male rats (35-40 days old) were treated with an acute dose of ethanol (1.0, 2.5 or 5.0 g/kg, i.g.) or vehicle that resulted in peak blood levels of 33, 72, and 131 mg/dl, respectively. Bromodeoxyuridine (300 mg/kg i.p.) was administered to label dividing cells and rats were killed at 5 h to assess proliferation or at 28 days to assess cell survival and differentiation. After 5 h, bromodeoxyuridine-immunoreactivity was reduced by 63, 97 and 99% in the rostral migratory stream and 34, 71 and 99% in the subventricular zone by 1.0, 2.5 and 5.0 g/kg of ethanol respectively. In the dentate gyrus, ethanol reduced bromodeoxyuridine-immunoreactivity by 29, 40, and 78% at the three doses respectively. The density of doublecortin immunoreactivity was decreased after 3 days and the number of bromodeoxyuridine+ cells remained decreased at 28 days when most hippocampal bromodeoxyuridine+ cells coexpressed neuronal nuclei, a neuronal marker. These studies indicate that the adolescent brain is very sensitive to acute ethanol inhibition of neurogenesis.

[The characteristics of the anticonflict action of fenazepam in rats selected by the method of forced swimming]. / Osobennosti antikonfliktnogo deistviia fenazepama u krys, otobrannykh s pomoshch'iu metoda vynuzhdennogo plavaniia.

A method of classification of outbred albino rats by means of forced swimming in a tank filled with water and equipped by freely turning wheels was developed. Using this technique a population of albino rats can be divided into three groups: highly active (HA), low active (LA) animals, and rats with intermediate activity. HA animals exhibit stable behaviour in forced swimming and conflict situation paradigms. They are also more sensitive to a benzodiazepine anxiolytic phenazepam in conflict situation test. At the same time, LA rats decrease their activity and are less sensitive to phenazepam. Both groups (LA and HA) are not homogeneous: each of them includes animals demonstrating quite another type of behaviour compared with a majority of rats.

[The characteristics of the effect of different classes of pharmacological substances on forced swimming in rats]. / Osobennosti vliianiia farmakologicheskikh veshchestv raznykh klassov na vynuzhdennoe plavanie u krys.

The authors have proposed a modified method of forced swimming in a water tank with freely rotating wheels, which differentiates psychotropic of major groups--stimulants, antidepressants, tranquilizers and neuroleptics whose activities can be tested by specific techniques. The advantages of the method includes the absence of a subjective factor in assessing the results, the possibility of automatic multichannel recording and direct input of data into the computer, the lack of necessary preliminary preparation (pharmacological, surgical, behavioral) of animals.

[Comparative evaluation of anticonvulsant and anti-arrhythmic effects of phenazepam, a benzodiazepine receptor agonist]. / Sravnitel'naia otsenka protivosudorozhnogo i antiaritmicheskogo éffektov agonista benzodiazepinovykh retseptorov fenazepama.

It was established on white mice that benzodiazepine receptor agonist phenazepam possessed a high anticonvulsant activity to antagonize bicuculline, corrasol, picrotoxin and thiosemicarbazide. It was also shown that phenazepam had a potent antiarrhythmic effect on ischemic and reperfusion cardiac arrhythmias in Wistar rats in situ. The effect was of a central nature since it was irreproducible in isolated heart. It seems to be due to the potentiating effect of phenazepam on the realization of GABA inhibitory control of centers of the heart regulation. The facts obtained evidence a possibility of using phenazepam not only as an anticonvulsant but also as an antiarrhythmic means.

[The effect of valproic acid on sleep structure and ethanol consumption in rats with various types of individual reactivity before and after stress exposure]. / Vliianie val'proevoi kisloty na strukturu sna i potreblenie étanola u krys s razlichnymi tipami individual'noi reaktivnosti do i posle stressornogo vozdeistviia.

The influence of valproic acid on sleep structure and alcohol motivation was studied in pretyped rats prior and following REM sleep deprivation. During EEG recording of wake-sleep cycle valporoic acid was shown to produce hypnotic action dependent on drug dosage in high active and low active animals. There was also shown that following REM sleep deprivation low active animals significantly reduced ethanol consumption under valproic acid influence. It seems likely from the results obtained that valproic acid could be used as hypnotic and antialcoholic drug.