Mesial temporal lobe epilepsy (MTLE) is the most common drug resistant form of epilepsy, and is associated with progressive memory impairment. Currently there is no pharmacological means to restore memory function in these patients, making it a significant unmet therapeutic need. This research thesis shows severe impairment in spatial memory acquisition and long term retention on a virtual Morris Water Maze (MWM) task in patients who had trans-slyvian selective amagdalohippocampectomies as treatment for MTLE. This pattern of impairment was also found in patients with MTLE and with MRI positive hippocampal sclerosis. Memory impairment in MTLE has been associated with depleted levels of stem cell derived new neurons, a process called neurogenesis which occurs almost exclusively in the dentate gyrus of the hippocampus; a brain area frequently associated with memory. Rats with kainate induced epilepsy also show learning and memory deficits on a MOlTis Water Maze We have shown that neurogenesis is depleted in chronic animal models of epilepsy, supporting the theory that there is a temporary increase in neurogenesis post insult but then a chronic depletion in the levels of neurogenesis. We are also one of a very small number of studies able to show abnonnal neurite sprouting in new neurons born in the chronically epileptic hippocampus. Uniquely we have been able to restore spatial learning ability and reverse the reduction in neurogenesis seen in chronically epileptic animals by administration of chronic dose of fluoxetine, although this did not alleviate the accelerated forgetting impairment. This opens a possible therapeutic avenue for h·eating spatial memory impairment in patients with MTLE.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:664607 |
| Date | January 2013 |
| Creators | Barkas, Lisa Jane |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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