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We investigated the pathogenic mechanisms of hippocampal structural changes and neuronal activation in a kainic acid (KA)-treated rat model using non-invasive high-resolution diffusion-weighted imaging, T2-weighted imaging, and manganese-enhanced magnetic resonance imaging (MEMRI). We found that high-resolution MRI can reveal KA-induced subtle lesions in hippocampus. The signal changes were first observed in the CA3 area and then the CA1 area, and were revealed to be focal edema and neuronal death in histopathological studies. MR signal intensity was higher in CA1 area than in CA3 area at 168 h post KA treatment due to the increase of proliferating astrocytes as shown by histopathological studies. MEMRI studies revealed signal hyperintensity in the CA3 pyramidal cell layer after KA treatment, and the MEMRI signal can be attenuated by diltiazem, an L-type calcium channel blocker. Histopathological study revealed attenuation of focal edema and neuronal swelling following diltiazem treatment. It indicated that KA-induced neuronal activation mainly developed in CA3, and calcium channels may play important roles in pathogenesis of KA-induced hippocampal lesions. We conclude that high-resolution MRI is able to identify KA-induced hippocampal damage, and that MEMRI can be used to investigate the role of calcium channels in the pathogenic mechanisms of neurological conditions.

Multiparametric MRI evaluation of kainic acid-induced neuronal activation in rat hippocampus