[Benefit of a short atherosclerosis prevention program on post-stroke vascular risk reduction]. / Intérêt d'un programme court de prise en charge globale de l'athérosclérose sur la réduction du risque vasculaire à distance d'un infarctus cérébral.

INTRODUCTION: Atherosclerosis is a major cause of ischemic stroke. Despite important therapeutic advances, the risk of recurrence of vascular events remains very high. The partial failure of these strategies is to some extent related to the lack of patient adherence to their treatments and to the fact that therapeutic targets are not reached. The aim of the present study was to evaluate the influence of a short atherosclerosis prevention program on vascular risk reduction in stroke patients. PATIENTS AND METHODS: Ninety-five patients with a first ischemic stroke related to atherosclerosis or with a high vascular risk profile were recruited. Three months later, a global evaluation of the atherosclerotic disease and of the vascular risk factors was performed combined with several education sessions on vascular risk factors and way of life. A follow-up evaluation was performed several months later to investigate the number of vascular events and the vascular risk profile. RESULTS: Median follow-up was 684 days after stroke. At follow-up, 91.3% of patients were taking a cholesterol-lowering drug, 95.6% an anti-thrombotic agent, and 78% an angiotensin converting enzyme inhibitor. A persistent decrease in tobacco use and an improvement in glycemic control were observed. During follow-up, 3.2% of patients died; none of the deaths were related to a vascular event. During the 22-month follow-up, 7.6% of patients experienced a major vascular event, acute coronary syndrome or stroke. CONCLUSION: Compared with results in the literature, this study illustrates the positive influence of a short atherosclerosis prevention program combining depiction of atherosclerotic lesions and education of vascular risk factors on the quality of long-term post-stroke prevention.

Early liver metastases in resectable periampullary cancer: Incidence and risk factors.

PURPOSE: The aim of the present study was to estimate the incidence of very early hepatic metastases (HMs) (<6 months) and their imaging patterns after cephalic duodenopancreatectomy (CDP) for periampullary carcinoma (excluding duodenal carcinoma) and to identify their associated risk factors. METHODS: From January 2003 to June 2016, all patients who underwent surgical treatment for periampullary carcinoma by CDP at our institution and with adequate pre- and postoperative CT scans were included. Univariate and multivariate logistic regressions were performed to determine factors associated with very early HM and recurrence. RESULTS: Of the 132 patients included retrospectively, 27 (20.5%) patients developed HMs. The mean time to diagnosis of HM was 103.9±55.2days. HMs were multiple in 81.4% of cases and bilobar in 59.3% of cases; their mean maximum size was 16.7±12.7mm. In univariate logistic analysis, lymphovascular emboli were significantly associated with HM (p=0.02). No independent risk factors for HM were found in multivariate analysis. In multivariate logistic analysis, two independent risk factors were identified for the occurrence of early recurrence: tumor size >23mm on preoperative CT scan (OR: 3.3; 95% CI: [1.2-9.3]; p=0.02) and tumor differentiation (poor vs. good: OR 15.5; 95 CI [1.5-158.3]; moderate vs. good: OR: 17.1; 95% CI: [1.9-154.4]; p=0.04). CONCLUSIONS: Nearly one in five patients developed HM after CDP within 6 months with a highly consistent pattern. A thorough preoperative assessment, combining CT scan and MRI with a delay of less than three weeks before surgery, appears essential. A routine systematic postoperative CT scan at 8 weeks is also required prior to initiating adjuvant chemotherapy. The type of surgical intervention does not seem to be a risk factor, although the risk of HM occurrence appears to be related to the lymphovascular invasion of the tumor and maybe its degree of differentiation, elements not assessable by imaging.

Effects of ketoconazole on the proliferation and cell cycle of human cancer cell lines.

The growth-inhibitory effects of ketoconazole, an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes, were tested in human colon and breast cancer cell lines. In the serum independent HT29-S-B6 colon cell clone, ketoconazole reduced cell proliferation and [3H]thymidine incorporation in a dose-dependent fashion, with a 50% inhibitory concentration of approximately 2.5 microM. Flow cytometry showed an accumulation of cells in the G0-G1 phase of the cell cycle and a concomitant decrease of the percentage of cells in S phase. Ketoconazole also inhibited [3H]thymidine incorporation in the hormone-independent breast cancer cells MDA-MB-231 and Evsa-T, with respective 50% inhibitory concentration of approximately 13 and 2 microM. The mechanism of action of ketoconazole is unknown. However, another lipoxygenase inhibitor, BW755C, inhibited only weakly [3H]-thymidine incorporation and accumulated the cells in S and G2. Conversely, clotrimazole and SKF525A, inhibitors of cytochrome P-450 enzymes, had effects similar to those of ketoconazole on HT29-S-B6 cells whereas metronidazole and secnidazole, other azole derivatives which do not inhibit cytochrome P-450 enzymes, had no effect. The results suggest that cytochrome P-450 enzyme(s) activity(ies) could be implicated in the antiproliferative effects of ketoconazole.

Proliferation of the human colon carcinoma cell line HT29: autocrine growth and deregulated expression of the c-myc oncogene.

Human colon adenocarcinoma cell (line HT29) are able to proliferate in a defined (serum-free) medium containing no added growth factors; in such conditions, their doubling time is 3 to 4 days (on serum-coated dishes) or 2 to 3 days (on an autologous extracellular matrix) compared with 1 day in the presence of fetal calf serum. In the presence of suramin, a polyanion disrupting the binding of growth factors to their receptors, the incorporation of [3H]thymidine in serum-free cultures is reduced (27.0 +/- 2.9% of control after 3 days of culture), suggesting involvement of autocrine growth factors in the autonomous proliferation of the cells. The expression of the proliferation-related oncogene c-myc was examined during various stages of growth and differentiation of the HT29 cells. The cellular contents of c-myc mRNA were similar in all experimental conditions studied: exponential phase; stationary phase; nondifferentiated as well as differentiated cells (by glucose deprivation); and also in serum-free medium containing or not suramin. An approximately 2-fold increase in the level of c-myc mRNA was observed in cells cultured for 3 days in suramin-containing medium and then incubated during 3 h in the absence of suramin (with or without 10% fetal calf serum). Southern blot analysis of the genomic DNA of HT29 cells did not reveal any rearrangement within the region containing the c-myc gene and the flanking sequences (approximately five kilobases upstream and approximately three kilobases downstream). The c-myc locus was weakly amplified (four to six copies per cell). These results indicate that the c-myc gene expression in HT29 cells is deregulated and does not require growth factor stimulation. The deregulation of the c-myc gene may be related to the reduced growth factor requirement of the HT29 cell line.

Growth-promoting effect, biological activity, and binding of insulin in human intestinal cancer cells in culture.

The biological action and binding of insulin were tested in two human intestinal cancer cell lines originating from the duodenum (HUTU 80) and the colon (HT 29). After serum deprivation for 24 hr, insulin stimulated cell division and the incorporation of labeled precursors into RNA, protein, and DNA for both cell lines. The action on the RNA and protein was rapid and significantly different (1.5 to 2 times that of control) 1 hr after adding insulin. These effects were dose dependent, present at physiological concentration in vivo (10(-10) M), and independent of the transport of precursors. For thymidine incorporation, the stimulation was delayed up to 8 hr and culminated with cell division 20 hr later. As previously shown for HT 20, HUTU 80 cells exhibited insulin-specific binding sites. Binding of 125I-insulin was saturable; reversible; and time, temperature, and pH dependent. Scatchard analysis of the binding data of the two cell lines gave curvilinear plots. Assuming the presence of two independent binding sites, the high-affinity constants were 6 to 8 X 10(8) M-1, and the number of high-affinity receptors was similar and accounted for 2000 to 3000 receptors/cell. For both cell lines, the effect of insulin on protein and RNA synthesis was significantly different from control at 1 hr when binding reached a maximum at 37 degrees. The biological action of insulin on growth and macromolecular synthesis was dose dependent and maximum at about 10(-8) M insulin, which corresponds to 70% displacement of 125I-insulin binding. Furthermore, the binding and the biological action of proinsulin were about 2% that of native insulin in the two cell lines studied. These results show that insulin acts as a growth factor for these two cell lines and that these effects are probably mediated by the interaction of insulin with specific receptors.

MDCT features of hepatocellular carcinoma (HCC) in non-cirrhotic liver.

PURPOSE: To describe the multidetector row computed tomography (MDCT) imaging features of HCC that develops in patients who are free from underlying liver cirrhosis and to determine if the MDCT presentation of this specific tumor differs from that of the more common HCC that develops in patients with liver cirrhosis using a retrospective case-control study. PATIENTS AND METHODS: The MDCT examinations of 38 patients with HCC in non-cirrhotic liver (group 1) were quantitatively and qualitatively analyzed and compared to those obtained in 38 patients with HCC in cirrhotic liver (group 2) matched for age and gender. Quantitative and qualitative characteristics of HCC of both groups were compared using univariate analysis. RESULTS: HCCs were significantly larger in group 1 (81.5mm±55.5) than in group 2 (44.5mm±39.1 SD; P=0.0015). In group 1, HCCs were more frequently single tumors (87%) than in group 2 (37%) (P<0.0001), encapsulated (92% vs. 47% respectively; P<0.0001), had more frequently fatty component (24% vs. 8%, respectively; P=0.0279) and internal hemorrhage (29% vs. 3%, respectively; P=0.0033). No significant differences were found between the two groups for location, hyperenhancement of HCC during the arterial phase, washout during the portal phase, endoluminal portal involvement by HCC, endoportal cruoric thrombus, invasion of adjacent organs and underlying liver steatosis. CONCLUSION: HCC in non-cirrhotic liver are larger than those observed in cirrhotic liver and more frequently present as a single encapsulated tumor. They have the same patterns of enhancement than HCC that develops in cirrhotic liver.

Development of insulin and epidermal growth factor receptors during the differentiation of rat preadipocytes in primary culture.

An homogeneous cell population isolated from the inguinal tissue of 3-day-old rats is able to proliferate in primary culture. In the presence of a physiological concentration of insulin (1.5 nM) it converts into cells exhibiting the morphology and the biochemical characteristics of adipocytes. Insulin and epidermal growth factor (EGF) receptors were studied during both the exponential growth and the adipose conversion phases of these cells. Binding experiments with 125I-labelled peptides were performed directly in the culture dishes. The number of high affinity insulin binding sites increased, during the entire culture period studied, reaching 18 days after plating the value of 10,600 x 2360. Control cells (cultured in the presence of anti-insulin antibody) exhibited an increase of the concentration of insulin binding sites from no more than 500 sites/cell to 6880 +/- 1710 sites/cell between dat 0 and 9 (corresponding to the exponential growth phase); this increase was followed by a rapid reduction in insulin receptors during the stationary phase. The density of EGF binding sites increased between day 0 and 4 (one cell cycle), whether the cells were maintained or not with insulin, and plateaued thereafter. Mature adipocytes freshly isolated from the inguinal tissue of 3-day-old rats had no detectable EGF binding sites, but their content in high affinity binding sites for insulin was similar to that of cells after complete adipocyte conversion in primary culture.

Characterization and repartition of epidermal growth factor-urogastrone receptors in gastric glands isolated from young and adult guinea pigs.

Physiological studies indicate that epidermal growth factor-urogastrone (EGF) acts on stomach epithelium as mitogen and modulator of acid secretion. Here, we studied the binding of 125I-EGF to gastric glands isolated from the guinea-pig fundus (acid-secreting part) and antrum. At 20 degrees C, the association of 125I-EGF to gastric glands was time-dependent (plateau at 90 min) and reversible (75-85% dissociation in 1 h). No degradation of the peptide was detected, but a time-dependent loss of binding capacity was observed. At apparent equilibrium (90 min, 20 degrees C) unlabelled EGF (80 pM to 80 nM) competed with 125I-EGF-binding in the same manner in antrum and fundus (50% inhibition, with 0.6 nM EGF). Whereas kinetics properties were similar in antrum and fundus, the binding capacity was 40-55% lower in fundus than in antrum in young animals (6-8 weeks). By contrast, in adult animals (20-30 weeks), binding was the same in both parts of stomach. Scatchard analysis showed that two orders of binding sites were present in all cases (Ki 0.34-0.47 nM, Ki 2.2-3.4 nM), and that the differences observed were only accounted for by number of binding sites. These results show that EGF possess high affinity binding sites on gastric epithelium. These sites, dependent upon the age of the animals, may be related to the modulations by EGF of gastric trophism and secretions.

[Echocardiography and biventricular resynchronisation]. / Echocardiographie et resynchronisation biventriculaire.

Biventricular resynchronisation has been recently shown to be an effective therapeutic option in patients with refractory dilated cardiomyopathy. Based on the finding of ventricular asynchrony, the aim of the method is to restore uniform contraction of the ventricular walls. However, the initial electrocardiographic criteria for selection of patients were only associated with a 70% rate of response. Consequently, it became necessary to refocus this method in patients with true ventricular asynchrony. Echocardiography is one of the non-invasive techniques which provides morphological and functional analysis of the myocardium with a high degree of accessibility. The multiplication of tools for echocardiographic quantification has been very valuable from a theoretical point of view for assessing ventricular asynchrony. In practice, techniques such as Doppler tissue imaging are being validated, but already offer the possibility of a multi-directional approach to this pathology. The diagnosis of asynchrony is based on a range of echocardiographic findings which not only improve the selection of patients but also optimise the programming of multisite stimulation.

Iodoamphetamine as a new tracer for local cerebral blood flow in the rat: comparison with isopropyliodoamphetamine.

Rats were injected with iodoamphetamine synthesized and labeled with 125I or with 125I- isopropyliodoamphetamine , a molecule of established value for the determination of local cerebral blood flow. The blood kinetics, tissue distribution, and brain uptake index for each tracer exhibited practically no differences. Autoradiographic quantification of the local cerebral blood flow, calculated according to the microsphere model, produced identical results for both molecules. However, compared with the values reported for other tracers, our values constituted an underestimation of white matter blood flow and a more real estimation of hippocampal flow. It is concluded from the brain uptake of the derivatives of both amphetamines during the first minutes following their injection that these tracers can be used as a chemical microembolus for the measurement of local cerebral blood flow.

Multiparametric imaging of blood flow and metabolism after middle cerebral artery occlusion in cats.

In anesthetized adult cats, acute stroke was produced by transorbital occlusion of the left middle cerebral artery. A battery of imaging techniques was used for simultaneous evaluation of regional blood flow, glucose utilization, protein synthesis, pH, and the regional tissue content of glucose, ATP, and potassium. The electrophysiological impact of stroke was monitored by EEG frequency analysis and recording of somatosensory evoked potentials. Two hours after vascular occlusion, a close correlation existed between the degree of electrophysiological changes and biochemical alterations, in particular with the extent of tissue acidosis, ATP depletion, decrease of tissue potassium content, and suppression of protein synthesis. However, there was only a poor correlation with blood flow and glucose utilization. Both of these exhibited a greatly inhomogeneous pattern with regions of reduced, normal, or increased rates. In areas remote from the infarct, the content of biochemical substrates was normal but blood flow was reduced globally by approximately 50% and glucose utilization by approximately 20%. An anatomically defined regional pattern of cerebral or cerebellar diaschisis was not observed. It is concluded that during the acute phase of stroke, imaging of blood flow and glucose utilization does not provide an accurate estimate of the actual functional or metabolic disturbance. For the clinical evaluation of the development or treatment of stroke, in consequence, alternative noninvasive techniques such as imaging of protein synthesis and/or pH may be more relevant.

Enterocyte differentiation is compatible with SV40 large T expression and loss of p53 function in human colonic Caco-2 cells. Status of the pRb1 and pRb2 tumor suppressor gene products.

Transfer of the SV40 large-T (LT) oncogene into isolated human and murine intestinal epithelial cells induced alterations of the ultrastructural organization and polarization of the resulting immortalized cell lines. We now demonstrate that the functional expression of the SV40 LT antigen in Caco-2 cells did not alter phenotypic markers of differentiation, including expression of villin, sucrase-isomaltase, brush border and dome formation. As compared to parental cells, the transfected Caco-2 LT9 cells exhibited similar growth curves and no invasive properties in vitro. The major oncogenic function of the SV40 LT antigen in transfected Caco-2 cells is associated with reduced latency times necessary for the manifestation of tumors in athymic nude mice. The Caco-2 cell line contained deleted and mutant p53 alleles (stop codon in position 204) and has no detectable truncated p53 protein by Western blot. Molecular complexes between the SV40 LT antigen and the retinoblastoma-related proteins pRb1 and Rb2 were clearly identified at the different phases of the growth curve. When compared to normal human colonic crypts, Caco-2 cell differentiation is related to partial redistribution of pRb1 into hypophosphorylated, antiproliferative forms. The pRb2 protein is found elevated in a subset of human colorectal tumors and their corresponding liver metastases. We conclude that: (1) Caco-2 cells exert a dominant control against the oncogenic functions of the LT antigen; (2) loss of p53 function is not restrictive for the establishment of polarity and differentiation of the enterocyte lineage; (3) the levels and phosphorylation status of the Rb1 and Rb2 proteins may play important roles in the proliferation and differentiation of normal and neoplastic human colonic mucosa.

Cerebral blood-flow tomography: xenon-133 compared with isopropyl-amphetamine-iodine-123: concise communication.

Tomographic maps of local cerebral blood flow (CBF) were obtained with xenon-133 and with isopropyl-amphetamine-iodine-123 (IMP) in 11 subjects: one normal, two tumor cases, and eight cerebrovascular cases. A highly sensitive four-face, rapidly rotating, single-photon emission tomograph was used. The Xe-133 flow maps are essentially based on the average Xe-133 concentration over the initial 2 min during and after an inhalation of the inert gas lasting 1 min. These maps agreed very well with the early IMP maps obtained over the initial 10 min following an i.v. bolus injection. The subsequent IMP tomograms showed a slight decrease in contrast amounting to appr. five percentage points in the CBF ratio between diseased and contralateral areas. It is concluded that Xe-133 is more practical: low cost, available on a 7-day basis, easily repeatable, quantifiable without the need for arterial sampling, and with low radiation exposure to patient and personnel. On the other hand, IMP gives an image of slightly higher resolution. It also introduces a new class of iodinated brain-seeking compounds allowing, perhaps, imaging of other functions more important than mere blood flow.

Insulin binding by a cell line (HT 29) derived from human colonic cancer.

Insulin binding was demonstrated in cultured HT 29 cells originating from a human colon carcinoma. At 37 degrees and in complete medium, the binding of [125I]insulin (1-4x10-10M) reaches a maximum in 40 min and the cell associated radioactivity remains constant for at least 4 h. No degradation of the hormone is observed under these conditions. The binding is proportional to the number of cells and its pH optimum is 7.8. In the presence of excess insulin 50% of the [125I]insulin is dissociated from the complex after 10 min. At equilibrium, insulin binding is specific: proinsulin is 25 times less potent than native insulin in competing with [125I]insulin and related polypeptide hormones are inactive. Scatchard analysis indicates two classes of binding sites (1400 sites/cell of "high affinity" e.g. 4.7 x 108 M-1, and 20 000 sites of "low affinity" e.g. 4 x 107 M-1). The binding of insulin to this non-target cell shows the same kinetic characteristics and specificity as found for insulin in its target cells, except that HT 29 cells do not degrade the hormone. The problem of the correlation between insulin binding and a biological effect in these cells remains to be elucidated.

Histamine and VIP interactions with receptor-cyclic AMP systems in the human gastric cancer cell line HGT-1.

In HGT-1 cells incubated at 20 degrees C for 15 min with 1 mM 3-isobutyl-1-methylxanthine (IBMX), histamine (10(-4)M) increased basal cAMP levels from 2.12 +/- 0.14 to 22.9 +/- 2 pmol per 10(6) cells, with a potency of 6.4 X 10(-6)M. IBMX was added in order to inhibit cAMP degradation by low and high Km cAMP-phosphodiesterases (cAMP-PDE). The use of specific H1, H2 agonists or antagonists indicated that the histamine effect was due to an interaction with typical H2 -receptors that are involved in gastric acid secretion. Cyclic AMP levels were also increased (10-fold) by vasoactive intestinal peptide VIP (3 X 10(-11) - 10(-8)M). Porcine peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) and secretin were respectively 80 and 3600 times less potent than VIP and did not produce additive effect when tested in combinations with VIP. This observation indicates that these two peptides, structurally related to VIP, are acting through the recognition sites for VIP. Combination of VIP and histamine results in additive stimulation on intact cells as well as on membrane-bound adenylate cyclase, suggesting the existence of two cell populations bearing respectively the two sets of receptors. Two other human cancer cell lines originating from nongastric tumors (HT-29 and HL-60) possess only VIP or histamine receptors, respectively, indicating the gastric cellular originality of the HGT-1 cells. It is concluded that HGT-1 cells possess both VIP and histamine H2 receptors with similar pharmacological properties to those characterized in normal human fundic glands (1,2). Therefore, this cell line can be a good model to study drugs used therapeutically during the treatment of patients for gastric ulcer or cancer.

Effects of VIP on the regulation of mucin secretion in cultured human pancreatic cancer cells (Capan-1).

The effects of Vasoactive intestinal peptide (VIP) on mucin secretion in the pancreatic cancer Capan-1 cell line were studied by Enzyme-linked-immunosorbent-assay (ELISA), and by light and electron microscopy using immunocytological methods. During the exponential growth phase, mucins were accumulated in the cytoplasm of cells and slowly exocytosed. In contrast, there was enhanced exocytosis of mucins during the stationary phase when the cells were well-polarized. Moreover, during this phase, VIP induced a dose-dependent rise in mucin content in the extracellular medium. The reaction with anti-M1 monoclonal antibodies, which recognize specifically the peptide core of gastric mucins, showed an accumulation of secretion granules near the apex of well-polarized cells together with fusion of the granule and plasma membranes after VIP stimulation. Moreover, mucin exocytosis was stimulated by Pituitary adenylate cyclase activating polypeptide (PACAP) and secretin. It was also increased after forskolin treatment suggesting that this mechanism was cAMP-dependent. Our results suggested that exocytosis of mucins could be under the control of VIP in pancreatic duct cells of the Capan-1 cell line.

[Brain rat histoenzymological changes induced by microsphere injection during ischemia (author's transl)]. / Modifications histoenzymologiqes du cerveau de rat au cours de l'ischémie provoquée par injection de microsphères.

The cerebral thrombosis of the rat with 35 micrometer labeled microspheres gives infarcted areas easily seen. After 15 min, in these areas, there is no change in NADH diaphorase-, succinic-dehydrogenase-, mono-amino-oxidase-, glucose-6-phosphate-dehydrogenase-, isocitric dehydrogenase-, lactic-dehydrogenase-, ATPase, alpha galactosidase-, acid phospatase activity. After 2, 4, 6 h all these activities diminish in the neuropil but they are preserved in the neurones for diaphorase, succinic-dehydrogenase and mono-amino-oxidase. The margin of infarcted areas shows a strong staining for acid phosphatase. Before 2 h there is not enzymatic changes neither oedema. This experimental model seems trustly and could be developped.

[Cardiac manifestations of amyloidosis by deposits of transthyretin and apolipoprotein A1. Report of 3 families]. / Manifestations cardiaques de l'amylose par dépôts de transthyrétine et d'apolipoprotéine A1. A propos de 3 cas familiaux.

Amyloidosis is characterised by extracellular deposits of a heterogenous protein. Compared with secondary forms, hereditary amyloidosis due to genetic mutations is rare. The authors report the cardiac manifestations in a French family of 5 sisters and 1 brother, three of whom presented with amyloidosis with deposits of transthyretin and apolipoprotein A1 due to a new genetic mutation.

Blockade of the different enzymatic steps in the synthesis of brain amines and memory (CAR) in hypobaric hypoxic rats treated and untreated with L. dopa.

L. Dopa associated with an extracerebral inhibitor of dopadecarboxylase is able to protect the rat against the deleterious effects of hypobaric hypoxia on a conditioned avoidance response. L. Dopa loses its protective effect against hypoxia if tyrosine hydroxylase, dopadecarboxylase, or dopamine beta hydroxylase is previously blocked. L. Dopa's protective effect must therefore be due to an indirect action on the endogenous catecholamine metabolism.

[Cerebral blood flow, metabolism and learning after a cerebral infarction in the rat (author's transl)]. / Débit cérébral, métabolisme et comportement a la suite d'un infarctus cérébral chez le rat.

Experimental microembolization of the rat brain has been used as a model for the production of cerebral microinfarction which resulted in a decrease in blood flow and secondary brain edema with changes in the oxidative metabolic pathways. The use of radioactive microspheres as embolizing agents allowed to determine the number of microinfarctions and their localization. In every microinfarct, oedema developed and it could be quantified by measuring the water percentage as soon as the fourth hour following the microembolization. The activity of oxygen-dependent enzymes was severely reduced in the ischemic area around which hyperemia was present. A quick decrease in the ATP and glucose levels and an increase in the lactate levels were observed, showing that the energetic metabolism was deviated towards the anaerobic pathway. On the fifth day following the microembolization, the oedema disappeared. The cellular metabolic activity and the cerebral blood flow almost returned to normal values within the same time. The simultaneously study of an avoidance response in a conditioned learning test showed a correlation between the reappearance of this response and the regression of the oedema.