Behavioral reactions of rats in the early postresuscitation period after systemic circulatory arrest of different duration.

Rats were exposed to systemic circulatory arrest for 10, 12, and 15 min. During the first 10 days after resuscitation exploratory activity of animals depended on the duration of systemic circulatory arrest and was determined by two opposite factors: high reactivity of the central nervous system contributing to intensification of exploratory activity, and impaired general state of survivors (inhibition of animal behavior).

Parameters of stress response at various stages of postresuscitation period.

Transient circulatory arrest (10 min) was followed by changes in rat adrenals and thymus and a decrease in blood calcium and protein contents typical of stress response. Maintenance under unfavorable conditions for a long time also produced changes in stress-target organs accompanied by a considerable shift in functional state of the central nervous system manifested in enhanced behavioral response to exogenous stimulation.

[Effect of perftoran on post-resuscitation recovery of the central nervous system]. / Vliianie perftorana na postreanimatsionnoe vosstanovlenie tsentral'noi nervnoi sistemy.

The effect of perfluorane on survival and restorative process in the brain were studied in rats subjected to 12-min arrest of systemic circulation. Perfluorane in a single dose of 5-10 ml/kg was injected intraperitoneally 30 min after the beginning of reanimation. The drug did not affect the postreanimation death of animals and time course of neurologic deficiency disappearance. Perfluorane activated behavioral reactions and prevented development of dystrophic changes in the brain structures of rats highly sensitive to hypoxia.

Some reasons for modifications of rat's conditioned behavior after resuscitation.

In rats survived systemic circulatory arrest and resuscitation, pathological changes such as increased excitability of the central nervous system and decreased volume of simultaneously acquired information considerably modulate conditioned activity. The interaction between these factors facilitates learning after formation of targeted behavioral pattern.

[The delayed effects of systemic circulatory arrest on the free-radical processes in the brain structures of rats with different types of behavior in the emotional resonance test]. / Otsrochennye éffekty ostanovki sistemnogo krovoobrashcheniia na svobodnoradikal'nye protsessy v strukturakh mozga krys s raznymi tipami povedeniia v teste émotsional'nogo rezonansa.

Male Wistar rats with different types of behavior in "emotional resonance" test ("active" and "passive") were studied one week after the global ischemia induced by cardiac arrest. Recovery of some physiological functions as well as free-radical-mediated processes and NO-synthase activity were studied in cerebral structures and blood serum. The "open-field" behavior normalized more rapidly in the "active" rats than in the "passive" ones, though the time course of the neurologic deficit compensation did not differ in these groups. A decrease in superoxide scavenging activity and in the content of 2-thiobarbituric acid-reactive material was revealed in the cerebral structures of both "active" and "passive" rats. Increased levels of free-radical generation in the hippocampus of the "passive" rats and in the cerebellum of the "active" rats were found. Higher NO-synthase activity was demonstrated in the cerebellum of the "passive" rats. Taken together, these data suggest that there are specific patterns of free-radical-mediated processes in the brain of rats with different types of behavior in "emotional resonance" test.

[Post-resuscitation neurosomatic deviations and the feasibility of their correction with a drug of metabolic action]. / Postreanimatsionnye neirosomaticheskie otkloneniia i vozmozhnosti ikh korrektsii preparatom metabolicheskogo deistviia.

Circulation in white rat males was stopped for 10 minutes by ligation of the intrathoracic vascular bundle of the heart. Proxipin in a dose 10 or 20 mg/kg was injected i.p. after restoration of effective cardiac activity and the next 3 days. Proxipin improved resuscitation outcomes, relieved symptoms of CNS excitability 4-6 months after resuscitation, changed adaptation to stress agents, protected against risk-factors of atherogenesis. However, proxipin-induced inhibition of the motor activity suppressed the free-choice ability to find food.

[Effects of active behavior in the postresuscitation period on the functional and morphological characteristics of the brain]. / Vliianie aktivizatsii povedeniia v postreanimatsionnom periode na funktsional'nye i morfologicheskie kharakteristiki mozga.

Efficacy of prolonged (days 10-60 after resuscitation) regular activation of behavior by labyrinth training of 4-staged food search conditioned reflex is studied in rats subjected to 15-min circulation arrest. This training affected the function of the central nervous system, which manifested by decreased anxiety and a higher activity in the open field test. This functional exercise prevented fall-out of neurons in the fifth layer of hemispheres, of cerebellar Purkinje's cells, and of pyramidal neurons in hippocampal sector CA1. These results support the hypothesis proposed by A. M. Gurvich on the possibility of regulating the postresuscitation recovery of the central nervous system by neurophysiological treatment of the brain.

The effect of systemic circulatory arrest on the process of free-radical oxidation and on NO-synthase activity in the brain structures of rats of different behavioral types in an emotional resonance test: the acute effects. / Vliianie sistemnoi ostanovki krovoobrashcheniia na protsessy svobodnoradikal'nogo okisleniia i aktivnost' NO-sintazy v strukturakh mozga krys s razlichnymi tipami povedeniia v teste émotsional'nogo rezonansa: ostrye éffekty.

Free radical-mediated processes and NO-synthase activity were studied in cerebral structures and blood serum of male Wistar rats with different types of behavior in emotional resonance test one hour after global ischemia induced by cardiac arrest. Oxidative stress accompanied by loss in NO-synthase activity was revealed in cerebral cortex after the ischemia. The oxidative stress was also evident in cerebellum and to a lesser extent in hippocampus. The majority of behavior-related biochemical differences were induced by cardiac arrest. These differences could be global or related to specific brain structures. Sometimes they became apparent in cerebral lateralization of biochemical indices.

Prophylaxis of encephalopathies and risk factors of atherogenesis development in the postresuscitation period in rats by means of succinic acid.

The effect of oral administration of succinic acid was studied in 66 rats exposed to 10 min cardiac arrest with further resuscitation. A total of 30 mg/kg of the drug were administered daily for 5 days starting with day 3 up to day 7 after resuscitation. The experiments have revealed that treatment with succinic acid caused normalization of the orienting behavior in an 'open field' test, decrease of the intensity of response to electric shock, normalization of free radical formation in the brain and serum and reduced cerebral morphological changes. The succinic acid prevented the increase of cholesterol, triglyceride and low density lipoproteins in the blood. The data suggested that after additional trials the succinic acid could be used to prevent development of postresuscitation encephalopathies (3 months after reanimation).

Postresuscitation changes in brain free radical-mediated processes and nitric oxide synthase activity in rats: effects of individual behavior in "emotional resonance" test.

Effects of 7-min cardiac arrest and individual behavior on free radical-mediated processes and nitric oxide synthase (NOS) activity was evaluated in brains of male Wistar rats one hour and one week after resuscitation. "Emotional resonance" test was used for the behavioral selection of rats. The test includes factors of significance for rats: the choice between large and lighted or small and dark space as well as signals of pain of another rat. Free radical generation (using chemiluminescence method), superoxide scavenging/generating activity, substances reacting with 2-thiobarbituric acid and NOS activity (by measuring mononitrosyl iron complex of NO with diethyl dithiocarbamate and endogenous brain Fe2+ by electron spin resonance spectroscopy) were determined in cerebral cortex, cerebellum and hippocampus. Cardiac arrest induced oxidative stress accompanied by the loss of NOS activity, as well as compensatory changes of free radical-mediated processes in cerebral cortex. Oxidative stress was also evident in cerebellum and, to a lesser extent, in hippocampus. Most of neurochemical differences between behavioral groups were induced by cardiac arrest. These differences were global, related to a specific brain region or became apparent in cerebral lateralization of biochemical indices.

[The effect of succinic acid on postresuscitation pathology of the CNS and of the body as a whole]. / Vliianie iantarnoi kisloty na postreanimatsionnuiu patologiiu TsNS i organizma v tselom.

The effect of oral succinic acid was studied in rats exposed to 10-min heart arrest followed by resuscitation. The drug was administered for 5 days in a dose of 30 mg/kg starting from day 3 up to day 7 after resuscitation. Succinic acid was found to normalize the orientation and exploration behavior of rats in the "open field" test, decreased the intensity of response to stress (electric shock), and normalized the radical formation in the brain tissue and blood serum, thus reducing the morphological changes in the brain. In addition, succinic acid prevented the development of risk factors of atherogenesis, namely, increase of the levels of blood cholesterol, triglycerides, and low and very low density lipoproteins. Further studies are needed to validate the addition of succinic acid to the armory of drugs preventing the development of postresuscitation encephalopathies in remote (3 months) periods.

[Effects of sodium succinate on functional, biochemical and morphological indicators of CNS repair in rats after 10-minute circulation arrest]. / Vliianie suktsinata natriia na funktsional'nye, biokhimicheskie i morfologicheskie pokazateli vosstanovleniia TsNS u krys posle 10-minutnoi ostanovki krovoobrashcheniia.

Therapeutic effect of sodium succinate on various functional, biochemical, and morphological parameters of CNS repair was studied in experiments on rats exposed to 10-min circulation arrest. The first series of experiments was devoted to studies of the effects of the drug, injected intraperitoneally directly after recovery of effective cardiac activity and during the subsequent 5 days in doses 20, 100, and 200 mg/kg, on the survival and recovery of the external neurologic status. The dose of 20 mg/kg proved to be the most effective. The second series of experiments was devoted to therapeutic effect of sodium succinate in the same dose injected from day 3 to day 7 after revival on the orientation and investigation behaviour in an "open field" test, on changes in radical formation in the blood serum and the brain, and on the cholesterol/lipid ratio in the brain, as well as on the morphologic changes in the cerebral hemispheres and the cerebellum. In contrast to untreated animals, the treated ones had a less intensive reaction in the "open field" test in response to acute stressor exposure, their cerebral and blood serum levels of free radical processes were reduced, the destruction of neuronal membranous elements was less intensive, as were dystrophic changes in the cerebral cortex and the cerebellum. The data permit a conclusion about antistressor and protective effect of sodium succinate in the postresuscitation period at the functional, biochemical, and morphological levels.

[Delayed postresuscitation degenerative changes in the brain and ways of studying their pathogenesis]. / Otsrochennye postreanimatsionnye degenerativnye izmeneniia v mozge i nekotorye puti issledovaniia ikh patogeneza.

Experiments with rats resuscitated after clinical death compatible with a complete and relatively rapid recovery of the neurologic status proved that prolonged (a follow-up of up to 9 months) and varying in time changes in a number of parameters of the higher nervous activity and behaviour occur in the postresuscitation period. Postresuscitation changes in behaviour correlate with the data on the degenerative changes in a number of cerebral structures of resuscitated rats progressing over 9 to 12 months. The available data of functional and morphological studies indicate the possibility of development of latent slowly progressing degenerative changes in the CNS of the organisms surviving clinical death and resuscitation. These changes reflect the development of postresuscitation disease and may become the cause of delayed encephalopathies. The problem of the possible mechanisms of development of progressive postresuscitation degeneration of the central nervous system and approaches to studies there of is discussed.

[Effect of the tranquilizer gidazepam on the behavioral reactions of rats in the first weeks after resuscitation]. / Vliianie trankvilizatora gidazepama na povedencheskie reaktsii krys v pervye nedeli posle reanimatsii.

The experiments have indicated that the first week of postresuscitation is marked by enhanced goal-investigating behaviour in the open field, by the accelerated learning of an operant reflex, and by decreased anxiety in the conflict situation test in male rats undergone a 10-min arrest of systemic circulation. There was a depressive behavior in the open field following 6-8 weeks with the normalization of operant reflex learning and the level of anxiety in the conflict test situation. Gidazepam (3 mg/kg, i.p.) produced a sedative effect in the first week after resuscitation, then 6-8 weeks later it displayed its anxiolytic and activating effect which is similar to this dose of the agent given to intact animals. The findings suggest that there are changes in the pattern of neurophysiological abnormalities, as well as a response of the benzodiazepine receptor complex to drugs during a resuscitative process, which may be one of the components of formation of a post-resuscitative central nervous abnormality.

[The characteristics of the adaptive behavior, neurological recovery and a morphometric analysis of the cerebral cortex in rats in the postresuscitation period]. / Osobennosti adaptivnogo povedeniia, nevrologicheskoe vosstanovlenie i morfometricheskii analiz kory mozga krys v postreanimatsionnom periode.

Rats recovered after a 10-min circulation arrest, were examined in the early postresuscitation period (within 10-12 days after resuscitation) in an open field (OF) test and during elaboration and reproduction of passive avoidance conditioned reflex (PACR); morphometric analysis of sensorimotor brain cortex was performed on days 4, 7, 14, and 30 after resuscitation. It has been shown that directly after compensation of external neurological deficit which took place in the majority of animals within 3 days the process of adaptation to new situation (OF test) in resuscitated rats, unlike the intact ones, was associated with high motor activity and not with the elaboration of stable correlations between various behavioral acts. At the same time disorders in learning and memory have been observed in PACR test. Morphometric studies have revealed changes in neuroglial relations by day 14 and considerable dystrophic neuronal changes by month 1 after resuscitation. All these disturbances took place with the overall density of neuron population preserved.

The dynamic of thermal fields of the brain of rats in the late post-resuscitation period under stress.

The temperature topography of the cerebral cortex of rats following clinical death and resuscitation was investigated with the technique of thermoencephaloscopy. Complete restoration of the neurological status of the animals was achieved over the course of one to two days. Marked disturbances in the background thermal maps and the thermal reactions of the cerebral hemispheres induced by a stressor were identified in the remote post-resuscitation period (up to two months). A pathological mosaicism of the thermal characteristics was detected under the conditions of relative rest, as were disturbances in the dynamics of the temperature reactions of the brain and in the character of the interhemispheric asymmetries under stress. The individual character of the post-resuscitation pathology which is found both in the baseline thermal maps as well as following a functional load is emphasized. The results of the investigation point to the importance of an individual approach in the rehabilitation therapy of the post-resuscitation illness.

[The dynamics of the brain heat fields of rats in the late postresuscitation period during stress]. / Dinamika teplovykh polei mozga krys v pozdnem postreanimatsionnom periode pri stresse.

By thermoencephaloscopy method the temperature relief of the rats cerebral cortex was studied after the clinical death and reanimation. The rehabilitation of the animals neurological status was completed in 1-2 days. In the remote postresuscitation period (up to 2 months), expressed disturbances were revealed of the background thermomaps and of thermal reactions of the cerebral hemispheres, evoked by the stress influence. Pathologic mosaics of thermal characteristics was revealed in conditions of relative rest and disturbance of dynamics of the brain temperature reactions and the character of interhemispheric asymmetries at stress influence. Individual character is pointed out of postreanimative pathology, which is manifest both in the background thermomaps and after the functional load. The results of the studies suggest the importance of individual approach in rehabilitation therapy of postreanimative disease.

[The indices of rat open-field behavior and the characteristics of the survival and functional recovery of the CNS following circulatory arrest]. / Pokazateli povedeniia krys v otkrytom pole i kharakteristiki vyzhivaniia i vosstanovleniia funktsii TsNS posle ostanovki krovoobrashcheniia.

In experiments on rats it has been shown that for prognostication of successful reanimation after the clinic death of different duration (5, 10, 15 min) correlative interactions between the parameters of behaviour in the open field before blood circulation cessation are more essential than their absolute values. Highly significant correlation coefficients (0.7 and more) between the majority of behaviour parameters were typical for the group of animals which had survived after a prolonged blood circulation cessation (15 min); for rats rehabilitated after 5- and 10-min cessation of the blood circulation--between the characteristics reflecting, basically, the motor-investigating component of the behaviour. In groups of died animals (independently on the duration of clinic death) correlation profile was restricted to characteristics determining only the character of the motor activity. Particular significance is underlined of emotionally psychic components of the behaviour for complete CNS restoration after a prolonged blood circulation cessation in comparison with the shorter ones.

[Changes in the sensitivity of the central nervous system to fenazepam at different stages of the recovery period after systemic circulatory arrest in rats]. / Izmenenie chuvstvitel'nosti tsentral'noi nervnoi sistemy k fenazepamu na raznykh étapakh vosstanovitel'nogo perioda posle sistemnoi ostanovki krovoobrashcheniia u krys.

Chronic experiments were conducted on rats subjected to 10-minute circulatory arrest to study the effect of intraperitoneal phenazepam (2 mg/kg) injection in various periods after resuscitation on some behavior indices. It was found that the changes in the quantitative (the degree of the effect) and qualitative (the extent of the effect) manifestations of the tranquilizing effect of phenazepam were determined by the different stages of restoration (from 1 to 21 days) after resuscitation. The results provide evidence of a definite stage character in the reactivity of the central nervous system in relation to pharmacological effects after resuscitation and, possibly, may reflect the functional reorganization of the work of the receptor complex and ion conductivity in the postresuscitation period.