F. Cohadon

UNILATERAL BRAIN INJURY IN THE RABBIT; REVERSIBLE AND IRREVERSIBLE DAMAGE OF THE MEMBRANAL ATPases

Modifications of some membranal enzymatic activities in rabbit brain edema induced by cold injury were studied. The edema was characterized by the tissue H2O content and the K+/Na+ ratio. Comparison of the respiratory rate of isolated mitochondria in the state 3 and 4 and the ADP/O ratio suggested an alteration in the ATP synthesis mechanism. The oligomycin sensitive ATPase activity was severely reduced in mitochondria isolated from edematous cells.

Effects of CDP-choline on phospholipase A2 and cholinephosphotransferase activities following a cryogenic brain injury in the rabbit

Within the tissue surrounding the necrotic lesion, following a cryogenic injury of the brain, there is a definite activation of phospholipase A2 (at 2 and 4 hr post lesion) that accounts, at least in part, for the phospholipid breakdown. There is also an activation of cholinephosphotransferase (at 2 hr post lesion) that may correspond to an early process of phospholipid resynthesis. Oral CDP-choline in this model is able to completely inhibit the activation of phospholipase A2, but has no detectable effect on cholinephosphotransferase activity. The beneficial effect of CDP-choline might be explained by a prevention of destruction rather than by an enhancement of reconstruction of phospholipids.

Modifications of Synaptosomal Na+‐K+‐ATPase Activity During Vasogenic Brain Edema in the Rabbit

Abstract: This study investigates the functioning of synaptosomal ouabain‐sensitive Na+‐K+‐ATPase in cold‐induced edema. During vasogenic brain edema development, the enzyme affinities for Na+ and K+ are progressively decreased paralleling the increase in the tissue water content, whereas maximal velocity of the reaction is not changed. On the basis of these data, it is likely that Na+‐K+‐ATPase impairment accounts for the intracellular uptake of water in this model of edema.

p53 Protein Expression in Grade II Astrocytomas : Immunohistochemical Study of 100 Cases with Long-Term Follow-Up

p53 protein expression was evaluated by immunohistochemistry in a homogeneous series of 100 supratentorial grade II astrocytomas with long-term follow-up. The staining was positive in 72 cases. The proportion of p53 positive tumors was slightly higher in younger patients. The tumor regrowths which derived from p53 positive tumors were themselves p53 positive, and this p53 immunopositivity was often stronger than in the initial tumors. All of the 10 gemistocytic astrocytomas included in our series were p53 positive, and age more than histological type appeared decisive in prognosis. p53 protein expression did not quite reach statistical significance as an independent predictive variable in multivariate analysis, whereas survival was related with age, mass effect, surgery and tumor location. Only a tendency to a longer survival was observed on the curves in younger patients with mildly positive tumors.

Redistribution of the flux-control coefficients in mitochondrial oxidative phosphorylations in the course of brain edema

This work describes the control exerted by dicarboxylate carrier and succinate dehydrogenase activities on the oxidative phosphorylations in rabbit brain mitochondria as an edema develops. Vasogenic edema leads to an uncompetitive inhibition of succinate dehydrogenase activity and to a large decrease of oxidative phosphorylations linked to succinate utilisation. Naftidrofuryl treatment in vivo restores both a high succinate dehydrogenase activity and a normal respiratory rate. In order to quantify the control of oxidative phosphorylations by the succinate dehydrogenase step, we applied the control analysis (Kacser, H. and Burns, J.A. (1973) in Rate Control of Biological Processes (Davies, D.D., ed.), pp. 65-104, Cambridge University Press, London; Heinrich, R. and Rapoport, T.A. (1974) Eur. J. Biochem. 42, 89-95). By using two inhibitors, one (phenylsuccinate) acting only on the dicarboxylate carrier and another (malonate) acting on both the dicarboxylate carrier and the succinate dehydrogenase, a method was developed to calculate the control coefficients of these two steps. The main result is that in mitochondria isolated from normal tissue succinate dehydrogenase exerted no control, but in the course of edema this enzymatic step became a controlling one: a transition from zero to a high control coefficient (0.5) was observed from the onset of intracellular edema for the threshold value of water/dry-weight tissue of 4.6.

The Early Phase of Cryogenic Lesions: An Experimental Model of Seizures Updated

Summary: : Following cryogenic lesions in 64 rabbits, epileptic activity and gray matter edema were correlatively investigated during the initial phase (23 h). Indexes were developed to allow a quantitative assessment of epileptic activity. The indexes demonstrated that the early phase of cryogenic epilepsy is a very rapid phenomenon during the first 4 h postlesion. Epileptic activity precedes brain edema, and in individual animals, there is a significant positive correlation between the total amount of epileptic activity and the total amount of edema. The relationship between epileptic activity and brain edema are most likely interrelated at the level of pathophysiological mechanisms and several mechanisms can be postulated.

Thiobarbituric acid-reactive material content and enzymatic protection against peroxidative damage during the course of cryogenic rabbit brain edema.

The relationship between free radicals reactions and the cell detoxifying system was investigated during the development of brain edema following a cryogenic lesion in the rabbit cerebral cortex. The amount of TBA-reactive material present six hours after freezing was less than in the controls, then increased at 48 and 96 hours. The activity of superoxide dismutase (SOD) decreased 6 hours post-injury; at the same time, we observed a stimulation of catalase activity. The glutathione peroxidase activity (GSH-Px) rose 96 hours post-lesion. The decrease of TBA-reactive products could result from an elimination rate that exceeds generation.

Low-grade astrocytomas: Prognosis factors and elements of management

BACKGROUND The literature provides information concerning prognosis of low-grade astrocytomas, but the series are quite heterogeneous in terms of clinical material, neuropathological evaluation, and statistical methods of analysis. Therapeutical indications are poorly defined. The last World Health Organization (WHO) histological classification provided a very precise definition of low-grade gliomas. METHODS Taking into account a recent study of our own and literature data, management guidelines of these tumors were proposed. RESULTS Grade I (pilocytic and subependymal giant cell astrocytomas) are surgically curable lesions. No adjuvant treatment is mandatory. Management of grade II astrocytomas is less clear-cut. Conservative management is probably possible in young patients without functional threat. The role of surgery on duration of survival has been properly established in very few series and was negative in many others. The role of radiotherapy has been demonstrated in a few subgroups of patients. In our study of ordinary astrocytomas, considering decades of age at diagnosis, survival curve analysis established three prognostic classes of age (before 50, between 50 and 60, and after 60 years of age). Based on our results and on recently published data, a branch decisional approach was proposed for management of grade II astrocytomas. Other grade II gliomas exhibit more favorable prognoses but could be managed in the same manner. CONCLUSIONS Ordinary grade II astrocytomas constitute a paradigm of difficult differential management. Further pertinent information on these tumors could come from the field of tumor biology, or be provided by very large and homogeneous groups of patients.

Energy-producing machinery in vasogenic brain edema

This paper investigates the functioning of mitochondrial energy-producing machinery in cold-induced edema and the level of energy charge available within the cell for cation transport.

Alterations of Membrane-Bound Enzymes in Vasogenic Edema

In recent years some of the pathophysiological mechanisms of vasogenic edema have been thoroughly studied and recognized, such as the initial breakdown of the blood-brain barrier, the exudation into the extracellular space of plasma fluid according to pressure gradients, the resolution by drainage into the ventricle, and/or uptake of proteins by astrocytes. Yet this type of edema should not only be considered as a simple extracellular event depending on physical forces. Soon after the onset of extracellular edema intra-cellular accumulation of fluid occurs, mainly in astrocytes and neuronal dendrites11,2. This intracellular component of vasogenic edema is poorly understood. Since rCBF is reduced in edematous lesions, cellular swelling has been considered to be the consequence of energy failure from lack of O2 and substrates. Some workers have reported a breakdown of energy reserves concomitant to a decrease of rCBF12,7. But in similar models, O2 supply has been found to be essentially normal8 and several authors have reported normal levels of high-energy compounds16.