Compensatory Adaptive Changes Research Articles

Tolerance to the Prophylactic Effects of Carbamazepine and Related Mood Stabilizers in the Treatment of Bipolar Disorders

SUMMARYTolerance development after successful long‐term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamazepine or lamotrigine on amgydala‐kindled seizures. In this model tolerance does not have a pharmacokinetic basis, but is contingent upon the drug being present in the brain at the time of amygdala stimulation. The occurrence of seizures in the absence of drug is sufficient to reverse tolerance and re‐establish anticonvulsant efficacy. Based on the model, we hypothesize that some episode‐induced compensatory adaptive changes in gene expression fail to occur in tolerant subjects and that episodes off medication re‐induce these changes and renew drug effectiveness. Approaches that slow or reverse tolerance development in the animal model are reviewed so that they can be tested for their applicability in the clinic. Criteria for assessing tolerance development are offered in the hope that this will facilitate a more systemic literature about its prevalence, prevention, and reversal. Careful longitudinal monitoring of episode occurrence is essential to understanding tolerance development in the affective disorder and its treatment.

Transient Enhanced Expression of Cdk5 Activator p25 after Acute and Chronic d‐Amphetamine Administration

The cellular and molecular mechanisms of sensitization in the addictive process are still unclear. Recently, chronic treatment with cocaine has been shown to upregulate the expression of cyclin-dependent kinase 5 (cdk5) and its specific activator, p35, in the striatum, as a downstream target gene of DeltaFosB, and has been implicated in compensatory adaptive changes associated with psychostimulants. Cdk5 is a serine/threonine kinase and its activation is achieved through association with a regulatory subunit, either p35 or p39. P35 is cleaved by the protease calpain, which results in the generation of a truncated product termed p25, which contains all elements necessary for cdk5 activation. The cdk5/p35 complex plays an essential role in neuronal development and survival. It has also been involved in neuronal trafficking and transport and in dopaminergic transmission, indicating its role either in presynaptic and postsynaptic signaling. In this study we report that the cdk5/p35 complex participates in acute and chronic d-amphetamine (AMPH)-evoked behavioral events, and we show a surprisingly transient enhanced expression of p25 and a lasting increased expression of p35 in dorsal striatal synaptosomes after acute and chronic AMPH administration. Pak1, a substrate for cdk5, is also enriched in the synaptosomal fraction of acute AMPH-treated rats. Our data suggest that the transient upregulation of p25 may regulate the activity of cdk5 in phosphorylating particular substrates, such as Pak1, implicated in the compensatory adaptive morphophysiologic changes associated with the process of behavioral sensitization to psychostimulants.

Effects of different modes of interval hypoxic training on morphological characteristics and antioxidant status of heart and lung tissues

The effects of various modes of interval hypoxic training differing by the intensity and duration of hypoxic exposure on the morphology and antioxidant status of the heart and lung tissues were studied. Interval hypoxic training mode with more severe, but shorter hypoxic component led to the prooxidant/antioxidant imbalance in the myocardial and lung tissues, which was paralleled by significant disorders in their morphology and function. Moderate hypoxic exposure of different duration promoted the maintenance of optimum antioxidant homeostasis and development of compensatory adaptive changes in tissue structure.

The hippocampus and neurotransplantation

The present article is a review of our own results from histological and electron microscopic studies of hippocampal neurotransplants with different levels of integration with recipient brains. A model providing complete isolation from the brain was obtained using transplants developing in the anterior chamber of the eye. The growth, development, and cytological composition of transplanted tissue was found to depend on factors such as the age of the donor embryo tissue, the genetic compatibility between the donor and recipient, and the level of integration with the brain. Ultrastructural analysis of intraocular and intracortical transplants showed that overall, nerve and glial cells have the characteristics of highly differentiated, mature elements; the numerical density and structures of synaptic contacts were similar to those in normal conditions. However, transplanted tissues contained morphological features providing evidence of continuing growth of several nerve processes and increases in non-synaptic and transport-metabolic intercellular interactions. The ultrastructural deviations observed here are regarded as the manifestations of compensatory-adaptive changes during the development of tissues in conditions deficient in natural afferent synaptic influences. It is also demonstrated that the axons of transplanted neurons lacking adequate cellular targets can establish functional synaptic contacts with neuronal elements in the recipient brain which are not their normal targets.

Ultrastructural analysis of liver biopsy specimens in diabetes mellitus associated with chronic opisthorchiasis.

Degenerative and compensatory adaptive changes in hepatocytes and other cell populations were detected in liver biopsy specimens from patients with diabetes mellitus concomitant with chronic opisthorchis invasion. The degenerative changes included alteration of hepatocyte nuclei, infiltration of the nucleoplasm with glycogen, and formation of cricoid nuclei. The cholestatic syndrome manifested in increased intracellular cholestasis. Perihepatocellular fibrosis characteristic of combined disease leads to "autonomization" of hepatocytes, "activation" of all poles of the plasmalemma, and formation of numerous microvilli not only at the biliary and sinusoidal poles, but also on lateral surfaces. These changes are directed at improvement of hepatocyte functional activity and intensification of metabolic processes.

Bilateral Vocal Cord Paralysis After Radical Cystectomy in a Patient with a History of Bulbar Polio

Bilateral Vocal Cord Paralysis After Radical Cystectomy in a Patient with a History of Bulbar Polio

Comparative morphometric and information analysis of the changes in different parts of the pancreas following ligation

The compensatory-adaptive changes in the guinea pig exocrine and endocrine pancreas following ligation are studied using morphometric and information methods. Objective criteria for evaluating organ changes are elaborated. The specific features of regeneration in exocrine and endocrine parts of the organ are described.

Maternal alcohol consumption before pregnancy and ultrastructure of neurons and interneuronal connections in rat offspring.

The ultrastructure of neurons and interneuronal connections in sensorimotor cortex have been studied in the offspring at 14- and 21-day-old female rats damaged by alcohol intoxication before pregnancy. We found three categories of ultrastructural changes in cortical neurons and interneuronal connections: delayed maturation of these structures, dystrophic and destructive changes and a signs of compensatory-adaptive processes. The first two categories of neuronal changes more marked at 14 days after birth. Later compensatory-adaptive changes become more significant, but dystrophic and destructive neuronal changes still remained. It is believed, that prenatal hypoxia-ischemia following alcohol consumption by female rats before pregnancy plays an important role in the pathogenesis of alcohol damage in cortical neurons and interneuronal connections in the offspring.

Elevation of calcium-dependent phospholipase C activity in the myocardium during adaptation to short-term stress

Sensorimotor cortex of rat 21- and 30-day-old offspring given prenatally moderate alcohol doses revealed signs of hemodynamic, ultrastructural capillary and compensatory-adaptive changes. The 60-day-old offspring displayed the tendency to hemodynamic and ultrastructural reversibility in remaining edema of the pericapillary processes of astrocytes. It is suggested that the deficiency of cerebral circulation is a delayed aftereffect of prenatal brain hypoxia. Under alcohol intoxication before pregnancy the edema was not observed. There was polymorphism of ultrastructure of cortical capillaries and immature vessels in the offspring.

Dynamical neural network organization of the visual pursuit system.

The central nervous system is a parallel dynamical system which connects sensory input with motor output for the performance of visual tracking. This paper applies elementary control system tools to extend dynamical neural network models to the visual smooth pursuit system. Observed eye position responses to target motions and characteristics of the plant (eye muscles and orbital mechanics) place dynamical constraints on the interposed neural network controller. In the process of constructing a model for the controller, we show two previous pursuit system models, using efference copy and feedforward compensation, are equivalent from an input-output standpoint. We introduce a controller model possessing a potentially highly parallel implementation and offer an example with supporting neural firing rate data. Changes in time delays or other system dynamics are expected to lead to compensatory adaptive changes in the controller. A scheme to noninvasively simulate such changes in system dynamics was developed. Actual physiologic data of adaptive responses to increased time delay is presented as an example of the utility of this parallel controller. Compensatory changes in our parallel controller model are easily predicted. These results suggest a productive interaction between neural network modeling, neurophysiology, and control systems engineering.

Morphological and functional changes in the digestive tract in the early stages of atherosclerosis

In experiments on dogs fed an atherogenic diet for two months the blood-serum levels of cholesterol, α-and β-lipoproteins, and serotonin were determined, and the serotonin concentration was studied in various parts of the digestive tract. In parallel investigations structural changes were studied in the vascular system in various parts of the digestive tract. Correlation was found between elevation of the cholesterol and serotonin levels in the blood and in certain parts of the digestive tract. The initial stages of atherosclerosis were detected in the blood vessels. In the digestive tract, besides compensatory-adaptive changes in the duodenum and proximal part of the small intestine, the initial stages of degeneration and atrophy were found in the distal portions. Comparative analysis of the biochemical and morphological data indicates an important role of morphological and functional disturbances in the genesis of the early stages of atherosclerosis.