Choy, M.; (2007) MRI investigations into the pilocarpine model of status epilepticus. Doctoral thesis , University of London.

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Abstract

Status epilepticus (SE) is a medical neurological emergency and may cause brain injury associated with epilepsy and cognitive decline. Evidence suggests that the hippocampus is particularly vulnerable to injury from SE and that the resulting hippocampal injury has been hypothesised to continue to evolve on to mesial temporal sclerosis associated temporal lobe epilepsy (MTS-TLE). This form of epilepsy is particularly difficult to treat with current medical therapies, and thus it is the most common epilepsy that requires surgical intervention. Therefore understanding the relationships between SE, hippocampal injury and MTS-TLE may provide the basis for development of novel therapies for treating post-SE injury. Clinical magnetic resonance imaging (MRI) studies have indicated that the hippocampus is injured following SE, but whether this injury will progress on to MTS-TLE remains unclear. To facilitate research, experimental models have been developed for investigating SE and its sequelae. Therefore, this study used the pilocarpine rat model for investigating SE and its related injury with multi-parametric MRI. The first part of this work investigated post-SE pathology with MRI and results indicate a characteristic injury profile for various brain regions injured by SE. Analysis of the hippocampus indicated a peak response 2 days following the insult showed a striking relationship to the degree of later injury, suggesting that imaging during the early period may predict later outcome. To investigate this response further, a combination of MRI and proteomic analysis was used and protein changes were identified. The second part of this study consisted of developing a method for imaging the onset and evolution of SE, and results suggest that limited perfusion may contribute to the hippocampal vulnerability to prolonged seizures. This work has identified an early MRI biomarker of later injury, and possible protein substrates for interventional therapy. Furthermore, evidence for the selective vulnerability to SE was found.

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