Kindling epileptogenesis has been associated with a number of different forms of neuroplasticity in the hippocampus, including mossy fibre sprouting and an increase in both intracellular calcium and zinc. The purpose of this thesis was to determine whether interfering with the influx of calcium via the voltage gated calcium channels would interfere with kindling- induced plasticity. Both kindled and control rats were injected with either 5 or 25mg/kg of the L-type voltage gated calcium channel blocker, nifedipine, or a control vehicle, DMSO (dimethylsulfoxide). The kindled groups received a kindling stimulation twice a day for 11 days. It was revealed that both doses of nifedipine significantly increased afterdischarge duration (p<0.001) and furthermore, both doses of nifedipine were capable of significantly interfering with the rate of kindling (p<0.001). Three weeks following the last kindling stimulation, rats were perfused and brain tissue was processed according to the Timm method. The density of Timm granules, an indication of the level of intracellular zinc in the mossy fibre pathway, was quantified. The results of this analysis revealed that 25mg/kg of nifedipine is capable of significantly reducing the amount of intracellular zinc in both the IML (p<0.04) and the CA3 (p<0.01) region of the mossy fibre pathway, regardless of whether the rats had received kindling stimulations or not. These results provide support for the notion that nifedipine (5 or 25mg/kg) is an effective anticonvulsant agent. These results also suggest that, at a sufficient dose (25mg/kg), nifedipine can reduce the amount of intracellular zinc in the mossy fibre pathway in both kindled and non-kindled animals, suggesting that nifedipine may be a useful therapeutic agent for pathologies that have been associated with zinc-induced neurotoxicity. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/24611 |
| Date | 06 1900 |
| Creators | Vaccarella, Liezanne |
| Contributors | Racine, Ronald, Psychology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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