Ethosuximide affects both pentylenetetrazole- and kainate-induced clonic seizures but differentiates between tonic–clonic seizures

1989 ◽  
Vol 67 (10) ◽  
pp. 1357-1361 ◽  
Author(s):  
Libor Velíšek ◽  
Ivana Kulhánková ◽  
Lenka Roztočilová ◽  
Pavel Mareš ◽  
Jana Velíšková ◽  
...  
Keyword(s):  
Age Groups ◽  
Similar Action ◽  
Young Rats ◽  
Wet Dog Shakes ◽  
Old Rats ◽  
Clonic Seizures

Young (25-day-old) and adult (90-day-old) rats pretreated with ethosuximide (62.5 or 125 mg/kg i.p.) were injected with either s.c. pentylenetetrazole (100 mg/kg) or i.p. kainate (10 or 14 mg/kg). The incidences and latencies of minor (clonic) and major (tonic–clonic) seizures were registered. Ethosuximide (125 mg/kg) completely blocked clonic seizures induced by the lower dose of kainate, and slightly suppressed or delayed those induced by the higher dose of kainate or pentylenetetrazole in both age groups. The effect of ethosuximide on major kainate-induced seizures (elicited in young rats only) was insignificant (ethosuximide only partially decreased the incidence of major seizures), whereas ethosuximide abolished major pentylenetetrazole-induced seizures in both age groups. Ethosuximide also failed to affect the latencies of kainate-induced automatisms (e.g., scratching, wet dog shakes). Similarities between kainate- and pentylenetetrazole-induced clonic seizures, as well as a similar action of ethosuximide on both, suggest a common generator for the pattern of clonic seizures.Key words: pentylenetetrazole, kainate, ethosuximide, seizures, rat.

scholarly journals Aging and acute exercise enhance free radical generation in rat skeletal muscle

1999 ◽  
Vol 87 (1) ◽  
pp. 465-470 ◽  
Author(s):  
J. Bejma ◽  
L. L. Ji
Keyword(s):  
Skeletal Muscle ◽  
Lipid Peroxidation ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Vastus Lateralis ◽  
Age Groups ◽  
Protein Carbonyl ◽  
Biological Aging ◽  
Young Rats ◽  
Old Rats

Reactive oxygen species (ROS) are implicated in the mechanism of biological aging and exercise-induced oxidative damage. The present study examined the effect of an acute bout of exercise on intracellular ROS production, lipid and protein peroxidation, and GSH status in the skeletal muscle of young adult (8 mo, n = 24) and old (24 mo, n = 24) female Fischer 344 rats. Young rats ran on a treadmill at 25 m/min and 5% grade until exhaustion (55.4 ± 2.7 min), whereas old rats ran at 15 m/min and 5% grade until exhaustion (58.0 ± 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of ROS and other intracellular oxidants production in the homogenate of deep vastus lateralis, was 77% ( P < 0.01) higher in rested old vs. young rats. Exercise increased DCFH oxidation by 38% ( P < 0.09) and 50% ( P < 0.01) in the young and old rats, respectively. DCFH oxidation in isolated deep vastus lateralis mitochondria with site 1 substrates was elevated by 57% ( P < 0.01) in old vs. young rats but was unaltered with exercise. Significantly higher DCFH oxidation rate was also found in aged-muscle mitochondria ( P < 0.01), but not in homogenates, when ADP, NADPH, and Fe3+ were included in the assay medium without substrates. Lipid peroxidation in muscle measured by malondialdehyde content showed no age effect, but was increased by 20% ( P < 0.05) with exercise in both young and old rats. Muscle protein carbonyl formation was unaffected by either age or exercise. Mitochondrial GSH/ GSSG ratio was significantly higher in aged vs. young rats ( P < 0.05), whereas exercise increased GSSG content and decreased GSH/GSSG in both age groups ( P < 0.05). These data provided direct evidence that oxidant production in skeletal muscle is increased in old age and during prolonged exercise, with both mitochondrial respiratory chain and NADPH oxidase as potential sources. The alterations of muscle lipid peroxidation and mitochondrial GSH status were consistent with these conclusions.

Aging alters neuronal nitric oxide release from rat mesenteric arteries: role of presynaptic β-adrenoceptors

2001 ◽  
Vol 101 (4) ◽  
pp. 321-328 ◽  
Author(s):  
Mercedes FERRER ◽  
Gloria BALFAGÓN
Keyword(s):  
Nitric Oxide ◽  
Age Groups ◽  
Electrical Field Stimulation ◽  
Mesenteric Arteries ◽  
Induced Response ◽  
Young Rats ◽  
No Release ◽  
Old Rats ◽  
Na Release ◽  
Subsequent Addition

This study examines the influence of aging on the neuronal nitric oxide (NO) and noradrenaline (NA) release elicited by electrical field stimulation (EFS; 200 mA, 0.3 ms, 1-16 Hz, 30 s) in endothelium-denuded mesenteric arteries from young and old rats, as well as the influence of the presynaptic β-adrenoceptors in that release. EFS induced frequency-dependent contractions. NG-nitro-l-arginine methyl ester (l-NAME) only enhanced EFS-elicited contractions in arteries from young rats. Capsaicin did not alter the EFS-induced contractions in either age group. Clenbuterol did not modify the contraction elicited by EFS in arteries from young or old rats either. A subsequent addition of l-NAME also induced an increase in the EFS-induced response in arteries from both age groups. In old rats, the presence of propranolol did not alter the response induced by EFS, and the subsequent addition of clenbuterol or clenbuterol plus l-NAME did not affect this response. In precontracted segments, sodium nitroprusside or clenbuterol induced similar relaxation in both age groups. None of the drugs used altered the response to exogenous NA or basal tone. In arteries preincubated with [3H]NA, EFS induced 3H release, which remained unmodified in the presence of clenbuterol or propranolol in young rats, whereas clenbuterol increased the 3H overflow in old rats, and this effect was abolished by propranolol. These drugs did not alter the basal 3H efflux and indicate that in rat mesenteric arteries EFS induces NA release in both age groups, and only NO release in young animals. Activation of presynaptic β-adrenoceptors increased NA and probably NO release in aged rats.

scholarly journals Anticonvulsant Action of a New Analogue of Allopregnanolone in Immature Rats

2010 ◽  
pp. 305-308
Author(s):  
P Mareš ◽  
H Kubová ◽  
A Kasal
Keyword(s):  
Clinical Trials ◽  
Acute Treatment ◽  
Age Groups ◽  
Neuroactive Steroid ◽  
Reference Drug ◽  
Anticonvulsant Action ◽  
Immature Rats ◽  
Effective Doses ◽  
Old Rats ◽  
Clonic Seizures

Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3αhydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology.

scholarly journals Anticonvulsant action of GABA-B receptor agonist SKF97541 differs from that of Baclofen

2008 ◽  
pp. 789-792
Author(s):  
P Mareš
Keyword(s):  
Receptor Agonist ◽  
Age Groups ◽  
Mixed Effects ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Generalized Seizures ◽  
Age Dependent ◽  
Old Rats ◽  
Clonic Seizures ◽  
Tonic Phase

GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups.

scholarly journals AMN 082, an agonist of mGluR7, exhibits mixed anti- and proconvulsant effects in developing rats

2008 ◽  
pp. 969-972
Author(s):  
P Mareš
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Age Groups ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Metabotropic Glutamate ◽  
Old Rats ◽  
Clonic Seizures ◽  
Motor Effects ◽  
Tonic Phase ◽  
Observation Period

Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype, was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in 12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN 082 before PTZ administration, therefore we performed another experimental series with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period tremor appeared in all age groups; sensitivity to this action decreased with age from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted motor effects makes clinical use of this drug highly improbable.

EFFECTS OF AGE AND TESTICULAR FUNCTION ON THE PITUITARY–THYROID SYSTEM IN MALE RATS

1979 ◽  
Vol 82 (1) ◽  
pp. 53-59 ◽  
Author(s):  
H. J. CHEN ◽  
P. G. WALFISH
Keyword(s):  
Age Groups ◽  
Male Rats ◽  
Male Rat ◽  
Testicular Function ◽  
Thyrotrophin Releasing Hormone ◽  
Thyroid Gland Function ◽  
Young Rats ◽  
Specific Effects ◽  
Old Rats ◽  
Gland Function

SUMMARY Old male rats of 22–24 months and young ones of 3–5 months were studied to find the effects of ageing, of orchidectomy and of orchidectomy and treatment with testosterone propionate (TP) on the basal serum concentrations of thyrotrophin (TSH) and on the total and free concentrations of tri-iodothyronine (T3) and thyroxine (T4) in the serum. The changes in TSH after treatment with thyrotrophin releasing hormone (TRH) were also observed. Intact old rats had significantly (P < 0·001) lower basal T4 and T3 as well as lower (P < 0·05) testosterone concentrations than were present in young rats. They also had higher basal TSH and per cent free T4 but lower absolute free T3 concentrations than had young rats. Two weeks after orchidectomy, basal TSH concentrations were slightly but significantly (P < 0·05) decreased in both young and old rats while T4 decreased significantly (P < 0·05) only in the young. The responses of TSH to TRH were also reduced by orchidectomy in both age groups with the old rats being less responsive than the young. Orchidectomy and treatment with pharmacological doses of TP produced similar effects on the pituitary-thyrotrophic response for both old and young rats but a greater effect occurred in the basal T4 response in young rats. In all groups basal TSH was influenced by orchidectomy or by treatment with TP but was always higher in the aged rat. Tri-iodothyronine concentration was always lower in the older rat and was not altered by orchidectomy or by treatment with TP in either young or old rats. These results indicate that (1) in the male rat these age-specific effects on the thyroid–pituitary system are probably due, not only to a reduction in thyroid gland function and plasma T4 protein-binding, but also to a concomitant hyporesponsiveness of the aged male rat pituitary thyrotroph to TRH stimulation and (2) there is probably a significant influence of testicular function on the pituitary–thyroid system of the male rat.

Age-related changes in rat intestinal transport of D-glucose, sodium, and water

1985 ◽  
Vol 249 (3) ◽  
pp. G328-G334
Author(s):  
G. Esposito ◽  
A. Faelli ◽  
M. Tosco ◽  
M. N. Orsenigo ◽  
R. Battistessa
Keyword(s):  
Cell Volume ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Age Groups ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Sugar Uptake ◽  
Transport Activity ◽  
Young Rats ◽  
Old Rats

Experiments were performed with everted sacs of jejunum and ileum and brush-border membrane vesicles from four different age groups of rats: very young, young, adult, and old. The changes with age in several parameters, such as cell electrolyte and D-glucose concentrations, cell volume, net D-glucose, Na+ and water transport, and D-glucose uptake into vesicles, were studied. Differences in transport activities in the four age groups of animals were observed. In the jejunum the greatest transport was found in young rats and less in adult, very young, and old rats. In the ileum, the greatest transport activity was found in very young and young rats, while in adult and old animals transport activity was negligible. The cell volume of the enterocyte was significantly smaller in old rats. Changes in cell electrolytes (increased Na+ and decreased K+) were observed only in the jejunum of old rats. The overshoot of D-glucose in brush-border membrane vesicles varied considerably in the four different age groups of animals. In other words, the capacity for sugar uptake into vesicles is greater in young rats than in very young or adult animals. In old rats there was no overshoot, and a slow linear increase of sugar entry was observed. The results indicate that the changes in D-glucose transport with age might be explained in part by the changes in the amount of sugar that crosses the brush-border membrane of the enterocyte.

Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration

2004 ◽  
Vol 287 (4) ◽  
pp. F797-F805 ◽  
Author(s):  
Ying Tian ◽  
Ryota Serino ◽  
Joseph G. Verbalis
Keyword(s):  
Collecting Duct ◽  
Water Channel ◽  
Age Groups ◽  
Urine Osmolality ◽  
Brown Norway ◽  
Water Restriction ◽  
Water Excretion ◽  
F1 Hybrid ◽  
Young Rats ◽  
Aquaporin 2

Renal concentrating ability is known to be impaired with aging. The antidiuretic hormone AVP plays an important role in renal water excretion by regulating the membrane insertion and abundance of the water channel aquaporin-2 (AQP2); this effect is primarily mediated via the V2 subtype of the AVP receptor (V2R). This study evaluated the hypothesis that decreased renal sensitivity to AVP, with subsequent altered renal AQP2 expression, contributes to the reduced urinary concentrating ability with aging. Our results show that under baseline conditions, urine osmolality is significantly lower in aged Fischer 344 and Brown-Norway F1 hybrid (F344BN) rats despite equivalent plasma AVP concentrations as in young rats. Levels of kidney V2R mRNA expression and AQP2 abundances were also significantly decreased in aged F344BN rats, as was AQP2 immunostaining in collecting duct cells. In response to moderate water restriction, urine osmolality increased by significantly lesser amounts in aged F344BN rats compared with young rats despite similar increases in plasma AVP levels. Moderate water restriction induced equivalent relative increases in renal AQP2 abundances in all age groups but resulted in significantly lower abundances in total kidney AQP2 protein in aged compared with young F344BN rats. These results therefore demonstrate a functional impairment of renal concentrating ability in aged F344BN rats that is not due to impaired secretion of AVP but rather appears to be related to impaired responsiveness of the kidney to AVP that is secondary, at least in part, to a downregulation of renal V2R expression and AQP2 abundance.

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

2007 ◽  
Vol 293 (5) ◽  
pp. L1261-L1270 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Mark R. Girton ◽  
Matthew J. Metropoulus ◽  
Mandar S. Joshi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Vascular Tone ◽  
Age Groups ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Sprague Dawley ◽  
No Donor ◽  
Early Postnatal Development ◽  
Old Rats

Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7- and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine augmented the K+-induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-day-old rats. Vasodilation to 0.1 μM of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 μM of the cGMP analog 8-(4-chlorophenylthio)guanosine-3′,5′-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.

Renal expression of osteopontin and alkaline phosphatase correlates with BUN levels in aged rats

1995 ◽  
Vol 269 (3) ◽  
pp. F398-F404
Author(s):  
C. T. Liang ◽  
J. Barnes
Keyword(s):  
Alkaline Phosphatase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Blot Hybridization ◽  
Northern Blot Hybridization ◽  
Tgf Beta ◽  
Young Rats ◽  
Beta Actin ◽  
Old Rats ◽  
Renal Expression

Renal expression of alkaline phosphatase (AP) and osteopontin (OP) in rats of different age was examined. Northern blot hybridization showed that AP mRNA was reduced moderately, whereas OP mRNA was stimulated drastically in old rats. Dot-blot quantitation analysis showed that AP mRNA decreased 30% in 24-compared with 6-mo-old rats. In contrast, OP mRNA increased 3.1- and 9.1-fold, respectively, in 12- and 24-mo-old rats. beta-Actin mRNA did not change with age. Blood urea nitrogen (BUN) increased 47 and 187% in 12- and 24-mo-old rats, respectively. Correlation analysis showed that BUN correlated negatively with AP mRNA and positively with OP mRNA. No correlation was observed with beta-actin. The expression of these markers was also examined in femurs. AP and OP mRNAs were marginally reduced in old bones. To test whether the correlation also exists in other types of renal insufficiency, we examined these parameters in young rats infused with parathyroid hormone (PTH). BUN was elevated 3.5-fold, whereas AP mRNA decreased 48%, and OP mRNA increased 15.3-fold in kidneys of PTH-treated rats. To elucidate the possible mechanisms that lead to the overexpression of OP in kidney, we examined the expression of transforming growth factor-beta 1 (TGF-beta 1) mRNA. No significant differences in TGF-beta 1 expression were observed between young and old rats and control and PTH-treated young rats. Changes in the expression of OP were also visualized by immunostaining of renal sections. Alterations in the levels of OP and AP were validated by Western blot analysis and enzyme assay of homogenate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document