In human studies of epilepsy, measurements of NAA have been widely used to assess neuronal loss and damage to localize seizure loci in a variety of different epileptic pathologies. Decreases in cerebral GABA (the primary inhibitory neurotransmitter) have been shown to be widespread and its metabolism and receptor systems are the target of a wide variety of anti-epileptic medications. Similarly, glutamate (the primary excitatory neurotransmitter) may be elevated in the epileptogenic hippocampus. However, mechanistic studies in humans are often difficult to pursue due to varying treatment regimens, medical history and the often poorly defined origin of the seizures. Therefore, mouse models of epilepsy are of great importance in evaluating the biochemical mechanisms underlying epiteptogenesis. Despite the clear ability of MR spectroscopic imaging to localize seizure foci, map the metabolic effects through networked structures, monitor alterations in critical neurotransmitter systems and by its non-invasive nature monitor the progression of epileptogenesis, its application in mouse models has been hinted. The lack of applications in the mouse brain is a direct reflection of a number of technological limitations including: 1) difficulties with shimming due to strong susceptibility effects associated with the small size of the mouse brain and proximity of bony and air-filled passages to brain tissue; 2) SNR limitations and volume resolution effects due to the relatively small size of the brain within the skull; 3) regional heterogeneity in metabolite content and its effects on interpretation of acquired data. Therefore the overall goal of this proposal is to develop the tools required to reproducibly acquire and analyze high-resolution spectroscopic images of NAA, glutamate and GABA in the mouse brain.
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| Kennan, Richard P; Machado, Fabiana S; Lee, Sunhee C et al. (2005) Reduced cerebral blood flow and N-acetyl aspartate in a murine model of cerebral malaria. Parasitol Res 96:302-7 |
