ABSTRACT
The present study aimed at establishing two models of experimental seizures by combination treatment with subconvulsive doses of PTZ and kainic acid in adult male mice and evaluating the modulatory role of cerebroselective dihydropyridine calcium channel blocker, nimodipine. The CD50 +/- SEM value for PTZ was found to be 20.00 +/- 0.92 mg/kg, ip in kainic acid (administered at per se subconvulsive dose of 1.00 mg/kg, ip) pretreated mice while CD50 +/- SEM value for kainic acid was found to be 0.30 +/- 0.08 mg/kg, ip in PTZ (administered at per se subconvulsive dose of 30.00 mg/kg, ip) pretreated mice. Nimodipine (5.00 mg/kg, ip) significantly protected the mice from seizure in both of the combination in vivo seizure models. The results suggested synergistic interaction between PTZ and kainic acid at subconvulsive dose combination while the protective efficacy of nimodipine suggested the role of calcium ion as an important mediator for the genesis of seizures.
Subject(s)
Animals , Calcium/metabolism , Calcium Channel Blockers/pharmacology , Convulsants/toxicity , Disease Models, Animal , Excitatory Amino Acid Agonists/toxicity , Kainic Acid/antagonists & inhibitors , Mice , Nimodipine/pharmacology , Pentylenetetrazole/antagonists & inhibitors , Seizures/chemically inducedABSTRACT
We determined if the dorsal raphe nucleus (DRN) exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11) or 1 æg/0.2 æl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10) through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment) and a low dose of dietary captopril (1 mg/g chow). From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 ± 2.3 to 22.3 ± 4.6 ml 0.3 M NaCl intake) whereas PB-DRN did not exceed 2 ml (P < 0.001). Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 ± 3.8 vs 21.6 ± 3.9 ml 300 min after fluid offer, P < 0.001). Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 ± 4.3 and 32.5 ± 3.4 ml on day 1 and day 2, respectively, vs 20.2 ± 2.8 ml on day 0, P < 0.001). These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.
Subject(s)
Animals , Male , Rats , Ibotenic Acid/toxicity , Excitatory Amino Acid Agonists/toxicity , Appetite/drug effects , Drinking/drug effects , Raphe Nuclei/drug effects , Sodium, Dietary , Appetite/physiology , Buffers , Captopril/pharmacology , Furosemide/pharmacology , Drinking/physiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Sodium Potassium Chloride Symporter Inhibitors/pharmacology , Phosphates , Rats, Wistar , Time FactorsABSTRACT
Increasing evidence supports the role of excitotoxicity in neuronal cell injury. Thus, it is extremely important to explore methods to retard or reverse excitotoxic neuronal injury. In this regard, certain dietary compounds are beginning to receive increased attention, in particular those involving phytochemicals found in medicinal plants in alleviating neuronal injury. In the present study, we examined whether medicinal plant extracts protect neurons against excitotoxic lesions induced by kainic acid (KA) in female Swiss albino mice. Mice were anesthetized with ketamine and xylazine (200 mg and 2 mg/kg body wt. respectively) and KA (0.25 microg in a volume of 0.5 microl) was administered to mice by intra hippocampal injections. The results showed an impairment of the hippocampus region of brain after KA injection. The lipid peroxidation and protein carbonyl content were significantly (P < 0.05) increased in comparison to controls. Glutathione peroxidase (GPx) activity (EC 1.11.1.9) and reduced glutathione (GSH) content declined after appearance of excitotoxic lesions. As GPx and GSH represent a major pathway in the cell for metabolizing hydrogen peroxide (H2O2), their depletion would be expected to allow H2O2 to accumulate to toxic levels. Dried ethanolic plant extracts of Withania somnifera (WS), Convolvulus pleuricauas (CP) and Aloe vera (AV) dissolved in distilled water were tested for their total antioxidant activity. The diet was prepared in terms of total antioxidant activity of plant extracts. The iron (Fe3+) reducing activity of plant extracts was also tested and it was found that WS and AV were potent reductants of Fe3+ at pH 5 5. CP had lower Fe3+ reducing activity in comparison to WS and AV. Plant extracts given singly and in combination 3 weeks prior to KA injections resulted in a decrease in neurotoxicity. Measures of lipid peroxidation and protein carbonyl declined. GPx activity and GSH content were elevated in hippocampus supplemented with WS and combination of WS + CP + AV. However, when CP and AV were given alone, the changes in the GPx activity and GSH content were not significant. Although the major factors involved in these properties of phytochemicals remain to be specified, the finding of this study has suggested that phytochemicals present in plant extracts mitigate the effects of excitotoxicity and oxidative damage in hippocampus and this might be accomplished by their antioxidative properties.