Abstract:DBA/2J mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner, susceptibility being maximal at 21 days of age and declining thereafter. DBA, as compared with AS-resistant C57BL/6J (C57) mice, had higher carbonic anhydrase (CA) activity in cerebral cortex, brainstem, and cerebellum homogenates at 21 days of age. CA activity was also increased in cytosolic (82%), microsomal (167%), and myelin (68%) subcellular fractions from cerebral cortex, and in cytosolic (51%) and mitochondrial (102%) f… Show more
“…In all three tissues examined there was a significant increase in CA activity in DBA control mice as compared with C57 control mice. This observation is in agreement with those previously reported (Engstrom et al, 1984b). In CC, CB, and BS, there was a significant decrease in CA activity in chronically treated as compared with control DBA mice.…”
Section: Chronic Actz Administration: Effect On Actz Eds0 Valuessupporting
confidence: 95%
“…Cerebral cortex (CC), cerebellum (CB), and brainstem (BS) tissues were collected, cleared of meningeal tissue, and homogenized. CA activity and protein content were determined on these homogenates according to the methods of Maren (1960) and Lowry et al (1951), respectively, as previously described by Engstrom et al (1984b). CA activity and protein content were also determined on brain tissues obtained from mice of the same age of both strains that had received no ACTZ.…”
Section: Chronic Actz Administration: Effect On Ca Activitymentioning
confidence: 99%
“…AGS susceptibility in DBA mice begins between 14 and 16 days, is maximal at 21 days, and is absent by 80 days of age. These studies demonstrated an increase in CA activity in brain from DBA mice as compared with C57BL/6J (C57) non-AGS susceptible mice at 21 and 110 days of age (Engstrom et al, 1984b). The role of increased CA activity is uncertain; it may be part of a neurochemical defect responsible for seizure propensity or part of a compensatory response aimed at delimiting the spread of seizure discharges.…”
The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
“…In all three tissues examined there was a significant increase in CA activity in DBA control mice as compared with C57 control mice. This observation is in agreement with those previously reported (Engstrom et al, 1984b). In CC, CB, and BS, there was a significant decrease in CA activity in chronically treated as compared with control DBA mice.…”
Section: Chronic Actz Administration: Effect On Actz Eds0 Valuessupporting
confidence: 95%
“…Cerebral cortex (CC), cerebellum (CB), and brainstem (BS) tissues were collected, cleared of meningeal tissue, and homogenized. CA activity and protein content were determined on these homogenates according to the methods of Maren (1960) and Lowry et al (1951), respectively, as previously described by Engstrom et al (1984b). CA activity and protein content were also determined on brain tissues obtained from mice of the same age of both strains that had received no ACTZ.…”
Section: Chronic Actz Administration: Effect On Ca Activitymentioning
confidence: 99%
“…AGS susceptibility in DBA mice begins between 14 and 16 days, is maximal at 21 days, and is absent by 80 days of age. These studies demonstrated an increase in CA activity in brain from DBA mice as compared with C57BL/6J (C57) non-AGS susceptible mice at 21 and 110 days of age (Engstrom et al, 1984b). The role of increased CA activity is uncertain; it may be part of a neurochemical defect responsible for seizure propensity or part of a compensatory response aimed at delimiting the spread of seizure discharges.…”
The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
“…Uptake of 36Cl-, 22Na+, and '"Iby astrocytes (C/M) of DBA, C57, and SW mice can either enhanced or inhibited by drugs acting on specific transport systems (Table 3). It is apparent that responses of these cultured astrocytes to drugs commonly used in transport studies are very similar to those in brain and other tissues reported previously (Chow et al, 1983~1, 1987(Chow et al, 1983~1, , 1990Engstrom et al, 19846;Woodbury et al, 1984).…”
Some basic properties of primary cultures of astrocytes derived from the cerebral cortex of an audiogenic seizure-sensitive strain of mice, DBA/2J (DBA), were studied with different approaches. The results were compared with those of audiogenic seizure-resistant strains, C57BL/6J (C57) and Swiss Webster (SW). Contents of intracellular water, protein, and DNA of DBA astrocytes were 0.673 +/- 0.019 ml/g cells, 0.082 +/- 0.006 g/g cells, and 0.0072 +/- 0.0005 g/g cells, respectively. These results are not different from those of either C57 or SW astrocytes. Intracellular concentration of K+, Na+, and Cl- ([K+]1, [Na+]1, and [Cl-]1) derived from the flame photometric and from the radioisotope uptake data of DBA astrocytes were 120.4 +/- 8.5, 25.9 +/- 3.2, and 26.8 +/- 1.8 mM/L cell H2O, respectively. [Na+]1 and [Cl-]1 in DBA astrocytes were lower than those in C57 and SW astrocytes. In DBA astrocytes, SITS decreased the cell/medium ratio (C/M) of 36Cl- and increased the C/M of 125I-; ouabain increased the C/M of 22Na+ and decreased the C/M of 125I-; bumetanide decreased the C/M of both 36Cl- and 22Na+; and NaClO4 decreased the C/M of 125I-. Similar results were observed in both C57 and SW astrocytes. Intracellular pH (pHi) as determined with 14C-DMO of astrocytes in HEPES-buffered saline solution averaged 7.04 +/- 0.03 for DBA, 7.01 +/- 0.02 for C57, and 6.97 +/- 0.02 for SW mice when pH of medium was maintained at 7.4. Modification of ion (HCO3-, Cl-, Na+, and K+) concentration and pH of culture medium all changed the pHi of astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
“…26, NO. l , 1985 thermore, Engstrom et al (1983) have recently demonstrated that in audiogenic seizure-susceptible DBA mice, carbonic anhydrase activity in cerebral and cerebellar cortex is highest at postnatal day 21, the period when the animals are maximally susceptible to audiogenic seizures. Thus, it appears that the increased activity of these two enzymes observed in various cerebral tissues of the audiogenicsusceptible mouse are compensatory for increased levels of neuronal activity.…”
Various parameters of anion and cation transport were measured in the cerebral cortex of neonatal (3-day-old) and adult rats following acute and chronic treatment with phenytoin (PHT). Acutely, PHT significantly inhibited the enzyme Na+, K+-ATPase in both neonatal and adult rats. This effect was accompanied by a significant increase in cerebral cortical Na+ content and a decrease in K+ content only in neonatal animals. Chronic treatment (two and four times a day for 7 days) of adult rats with PHT significantly reduced Na+ content without affecting whole homogenate Na+, K+-ATPase activity. The activity of this enzyme was markedly increased in the myelin- (glial product) and slightly decreased in the synaptosomal- (neuronal) fractions following chronic (four times a day for 7 days) PHT treatment. These results suggest that PHT differentially affects the two forms (neuronal and glial) of the enzyme Na+, K+-ATPase. The possible relevance of this hypothesis in relationship to the anticonvulsant and excitatory properties of PHT is discussed. Chronic (two and four times a day for 7 days) PHT treatment increased both DNA content and activity of the glial marker enzyme carbonic anhydrase. Activity of the mitochondrial enzyme HCO3- -ATPase was also increased following chronic PHT treatment. These two enzymes are intimately involved in the regulation of HCO3- -Cl- transport across glial cell and mitochondrial membranes, and these results suggest that PHT is able to affect beneficially glial regulatory processes. The ability to enhance glial regulation of anions and cations in extracellular fluid provides new and important insights into the mechanism of the anticonvulsant action of PHT.
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