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D W McCandless

Publications and source records attributed to D W McCandless.

At least 37 records · Page 2Linked to original sources
PubMed1982

Isoniazid induced seizures and cerebral cortical and cerebellar energy metabolism.

Isoniazid is a useful chemical convulsant in that metabolic events associated with the preseizure state can be easily examined. In the present study, net levels of glucose, glycogen, ATP, and phosphocreatine were measured using enzymatic techniques in control mice, and in those injected with isoniazid. Results from this study showed a differential effect of isoniazid on cells from the cerebral cortex and the cerebellum. In the preseizure stage, the high energy phosphates ATP and phosphocreatine were decreased in layer 1 and the pyramidal cell layer of the cerebral parietal cortex, but were unchanged in the cerebellum. At the onset of seizures, metabolites were decreased not only in cortical layers, but in the molecular layer and Purkinje cell rich layer of the cerebellum as well. The somewhat delayed response of the cerebellum emphasizes the differential nature of metabolism in various brain regions. Such a delay in cerebellar energy response to perturbation may be conducive to the seizure state. In another series of mice, either sodium valproate or clonazepam was administered prior to isoniazid, and metabolite studies repeated. Results showed that at a time when each anticonvulsant acted to eliminate overt seizure activity, the reduction in ATP and phosphocreatine was not as great as it was in seizing mice treated with isoniazid alone.

Adenosine Triphosphate↗
PubMed1982

Metabolic profile of hippocampal regions after bilateral ischemia and recovery.

Microanalysis methods were used to determine the effect of bilateral carotid occlusion on net levels of energy metabolites in discrete cellular regions of the hippocampus and dentate gyrus of the Mongolian gerbil. Glucose, glycogen, ATP and phosphocreatine levels were not decreased after one minute of bilateral occlusion. Three minutes of ischemia, however, produced a dramatic fall in net levels with no further decrease observed at fifteen minutes. Re-establishment of blood flow for five minutes after a fifteen minute ischemic episode resulted in replenishment of metabolites to pre-ischemic levels. Glucose was increased two to three times in sham-operated animals as compared to control (non-operated) animals. The increase was the result of the Na-pentobarbital anesthetic employed. The present data indicate that regions of the hippocampus and dentate gyrus respond in a uniform manner to bilateral occlusion of the carotid arteries. Further, most cells maintained enough viability to resume production of high-energy phosphate and carbohydrate metabolites.

Adenosine Triphosphate↗
PubMed1982

Audiogenic seizure-induced changes in energy metabolites in cerebral cortical and cerebellar layers.

Audiogenic seizure-prone mice (DBA/2J) were exposed to a broad band noise source. A reproducible response consisting of wild run, clonus, and tonic stages resulted in all mice. Layers 1 and pyramidal from the parietal cortex and the molecular and Purkinje cell-rich layers from the cerebellar vermis were separately analyzed for glucose, glycogen, ATP, and phosphocreatine. Results showed a biphasic cerebellar response, with decreases in high energy phosphates occurring during the wild run and tonic stage. In the cortex, similar changes occurred in the pyramidal cell layer, but the decreases were not as pronounced as those in the cerebellum. Cells from layer 1 of the parietal cortex were not affected as much as those of the pyramidal layer, suggesting a differential effect between neuronal and nonneuronal cell populations. The greater response of the cerebellum could indicate an attempt to reduce the severity of both the wild run and the tonic extension seizure.

Acoustic Stimulation↗
PubMed1981

Insulin-induced hypoglycemic coma and regional cerebral energy metabolism.

Swiss-Albino female mice weighing 20 g were rendered hypoglycemic by injecting insulin (2 units/kg). Animals were sacrificed at 40 min (pre-coma), 2 h (coma) and 4.5 h (recovery) after insulin injection by rapid submersion in liquid N2. Following sectioning at 20 micrometer, samples from the ascending reticular activating system and the inferior colliculus were freeze-dried and assayed for glucose, lactate, ATP and phosphocreatine (PCr). There was a preferential effect of hypoglycemia on ATP and PCr in cells of the ascending reticular activating system. ATP was depleted 30%, and PCr 55% in the pre-coma stage. ATP and PCr in cells from the inferior colliculus were not decreased. This selective effect on cells of the ascending reticular activating system followed by coma suggests that the coma per se may not represent total failure of the organism, but rather a compensatory mechanism designed to permit the animal to correct its compromised energy status.

Adenosine Triphosphate↗
PubMed1981

The effect of 6-aminonicotinamide on energy metabolism in rat embryo neural tube.

6-Aminonicotinamide (6-AN) is a potent metabolic inhibitor which produces central nervous system malformations when administered to pregnant rats. Since the antimetabolite interferes with energy yielding pathways, the present study was undertaken to determine the effect of maternally administered 6-AN on energy metabolism of the neural tube in developing embryos. On day 9 of gestation, pregnant rats were injected with 2 mg/kg 6-AN, and embryos removed 12 or 24 hours later. Glucose, glycogen, lactate, ATP, PCr, and GABA were measured in neural tube sections using fluorometric techniques. Only ATP and PCr showed changes as compared to appropriate controls. These two metabolites were increased 29% and 37%, respectively, by 6-AN administration. The mechanism of these alterations in metabolites is unclear, but may be related to decreased metabolic demand.

6-Aminonicotinamide↗
PubMed1981

Effect of acute ammonia intoxication on energy stores in the cerebral reticular activating system.

Ammonia intoxication causes loss of consciousness. One postulated mechanism for this stipulates impaired energy metabolism in critical brain sites. The ascending reticular activating system in the brainstem may modulate consciousness. Accordingly, the present study, using micromethods, assessed energy stores in cells from the reticular activating system of mice acutely intoxicated with ammonia. In the early coma period (3.5 min after ammonia) phosphocreatine, adenosine triphosphate and glucose fell significantly while glycogen decreased later. Subsequently during coma, the high energy phosphates returned to normal and supranormal. The maximal fall in these metabolites was not accompanied by a rise in lactate, implying lack of local hypoxia or acidosis. The cells of the posterior coliculus in the same animals failed to show a significant fall in energy stores. These data suggest a selective effect of ammonia on energy metabolism in the cells of the reticular activating system of the brainstem.

Adenosine Triphosphate↗
PubMed1981

Cerebral energy metabolism during the onset and recovery from halothane anesthesia.

Halothane (1%) was administered to twenty-two gram female Swiss-Albino mice which were sacrificed at times of 15 seconds, 45 seconds, 79 seconds and 5 minutes. Additional animals were exposed for 5 minutes and sacrificed 10 minutes after removal from halothane (recovery). Selected energy metabolites were measured in 100-500 nanogram samples from the inferior colliculus and the ascending reticular activating system. Results from this study showed an increase in glucose levels at 79 seconds, when the animals first lost their righting response. The glucose increase was similar in the inferior colliculus and reticular formation. ATP and phosphocreatine were increased at 45 seconds, and during the sleep period in the ascending reticular activating system, and returned to normal during the recovery period. In the inferior colliculus. ATP was similarly increased from 45 seconds throughout the time course, whereas phosphocreatine was elevated at 79 seconds, and during recovery only. These data suggest a decrease in utilization of energy metabolites during halothane anesthesia, both in cells of the inferior colliculus and ascending reticular activating system.

Adenosine Triphosphate↗
PubMed1981

Distribution of cyclic nucleotides in layers of the cerebellum after decapitation.

The distribution of the cyclic nucleotides was examined in layers of the mouse cerebellum following decapitation. Cyclic AMP increased and cyclic GMP decreased in all three layers of the cerebellum examined. The increase in cyclic AMP in the granular layer was far greater than in either the molecular or white layers. In the cerebellum from control mice, the cyclic GMP concentration was highest in the molecular layer and lowest in the white layer. Even after decapitation, this cyclic GMP gradient in the cerebellum was maintained.

Animals↗
PubMed1981

Metabolic turnover in the reticular activating system in ammonia induced coma.

Previous studies have implicated the ascending reticular activating system (RAS) as playing a vital role in ammonia induced coma. It has been shown, for example, that cells of the RAS have selective decreases in the level of energy metabolites such as ATP and phosphocreatine as compared to adjacent tissue during ammonia induced encephalopathy. To determine the utilization rate of metabolites during ammonia induced coma, we have examined the turnover rate of four key energy metabolites in 20-22 gram mice. Results from this study show decreases in the turnover of glucose, glycogen, and phosphocreatine. The derived value for the turnover of energy metabolites was decreased by 49% as compared to that of control mice. These data suggest that energy utilization is decreased at a time when the physiological output of the RAS is also diminished and the animal is comatose.

Adenosine Triphosphate↗
PubMed1980

The effect of unconjugated bilirubin on regional cerebellar energy metabolism.

Many previous studies have examined the effects of unconjugated bilirubin on cerebral energy metabolism. The results have been equivocal largely because the samples for assay included contiguous less affected tissue. The present study was undertaken to obviate this problem. Kernicteric Gunn rat cerebella were sectioned, freeze dried, and Purkinje cell rich layers prepared, as well as adjacent molecular and granular layers. These layers were assayed, along with suitable controls, for glucose, glucogen, ATP, and phosphocreatine. ATP and phosphocreatine were decreased in the Purkinje cell rich layer only; molecular and granular layers were unaffected. Glucose and glycogen were increased in all three layers. These results support the concept that in vivo, bilirubin exerts its toxic effect by uncoupling oxidative phosphorylation.

Animals↗
PubMed1979

Sparing of metabolic stress in Purkinje cells after maximal electroshock.

Experimental seizures were induced in mice by application of 50 mA for 0.2 sec via corneal electrodes. The reproducible conclusive behavior was characterized by a sequence of 2 sec of tonic flexion, 13 sec of tonic extension, and 8 sec of clonus followed by a postictal depressive stage. The animals were frozen and tissues were prepared for analysis according to Lowry and Passonneau [Lowry, O. H. & Passonneau, J. V. (1972) A Flexible System of Enzymatic Analysis (Academic, New York)]. Freeze-dried samples (1-10 ng) of pyramidal cell bodies and adjacent neuropil from the parietal cortex and of Purkinje cell bodies and adjacent neuropil from the cerebellum were analyzed for glucose, ATP, and P-creatine (0.01-0.05 pmol). There were marked decreases in these energy stores after the maximal electroshock in three of the areas examined. In the Purkinje cell bodies, however, the metabolic stress was dampened; glucose concentrations decreased, but the levels of ATP were maintained and, to a lesser extent, those of P-creatine. The results indicate that the output from the Purkinje cells is less than in the other regions examined in the excitable stages of the convulsion. The lesser energy debt probably reflects lower energy demand as well as a lower discharge intensity. The fact that Purkinje cells are spared from the metabolic stress imposed on other regions may be a partial explanation of the seizure activity. A diminished output from the Purkinje cells could be a situation that permits cortical convulsive activity.

Adenosine Triphosphate↗
PubMed1976

Glycolytic metabolism in cultured cells of the nervous system. IV. The effects of thiamine deficiency on thiamine levels, metabolites and thiamine-dependent enzymes on the C-6 glioma and C-1300 neuroblastoma cell lines.

C-6 glioma and C-1300 neuroblastoma cells were cultured in thiamine deficient and control media. Thiamine levels, transketolase and pyruvate decarboxylase activities, and high energy phosphate metabolites were all measured in deficient and control cells. Thiamine levels in the deficient cells were found to be below the level of detectability. Pyruvate decarboxylase activity was more susceptible to thiamine deficiency in both cell lines than transketolase. In spite of the large decrease in pyruvate decarboxylase activity, high energy phosphate metabolites were not decreased in either cell line. These data indicate that C-6 glioma and C-1300 neuroblastoma cells have the capacity to maintain normal energy metabolites in the presence of large changes in thiamine levels and thiamine dependent enzyme activity.

Cell Line↗