Effectiveness of GK-2, a Nerve Growth Factor Mimetic, in Preventing Post-Resuscitation Changes in the Brain.

Neurological status was assessed and the numbers of neurons per 1 mm in pyramidal neuronal layer length in CA1 and CA4 hippocampal fields and cerebellar Purkinje cells were evaluated in albino male rats on post-resuscitation day 14 after 12-min cardiac arrest. Intraperitoneal administration of GK-2 (1 mg/kg 30 min after resuscitation and within the next 3 days with an interval of 24 h) accelerated neurological recovery of the animals, sharply reduced the intensity of cerebellar Purkinje cell death, and prevented loss of pyramidal neurons in the hippocampus. These results show the effectiveness of systemic administration of the nerve growth factor mimetic GK-2 in improving structural and functional state of the brain in the post-resuscitation period.

Ca(2+) transport into sarcoplasmic reticulum and immediate-early response proteins in the myocardium of rats resuscitated after systemic circulatory arrest.

Activity of antioxidant defense enzymes and content of stress protein HSP70 in the heart increased in passive and, to a lesser extent, in active rats on day 7 of the postresuscitation period after systemic circulatory arrest. The resistance of membrane structures in the heart to endogenous damaging factors in passive rats was lower than in active animals. The degree of compensation in active rats was much higher than in passive animals at these terms of the postresuscitation period.

Mechanism of the effect of postresuscitation changes in the brain on the dynamics of extinction of orientation and exploratory response in rats.

The type of open-field behavior (determined in preliminary tests) was preserved after 10-min circulatory arrest. Postresuscitation changes in the bran modified orientation and exploratory activity under conditions of its partial extinction before clinical death. High behavioral activity of rats in the first open-field session after resuscitation was related to the impairment of memory traces, while that in the follow-up period was associated with the formation of a pathological self-maintaining system between components of orientation and exploratory behavior.

Active and passive behavior of animals during the postresuscitation period.

Behavioral reactions (open-field test, elevated plus-maze, pain stress, and feeding behavior) were studied in various periods after clinical death caused by circulatory arrest for 10 or 15 min. We revealed two different phases of behavioral changes: active behavior directed at attaining a specific goal and passive behavior directed towards isolation of the organism from external signals and functional minimization. Active behavior determined by pathological excitation in the central nervous system increased the severity of structural damage to hippocampal CA1 neurons during the postresuscitation period.

Mechanisms of adaptation to flow reactions in rats after systemic blood arrest.

The rats survived 10- or 15-min systemic blood flow arrest were exposed to various extreme factors within the following 2 months. It was found that the processes leading to functional isolation of CNS play a protective role: they moderate behavioral response to acute stress and alleviate the degree of neuron damage induced by long-term stress during acquisition of a complex food-procuring reflex.