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Brain Advance Access published online on September 4, 2007

Brain, doi:10.1093/brain/awm207
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Yi-Hua Hsu1,*, Wang-Tso Lee3,* and Chen Chang1,2

1Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, 2Institute of Pharmacology, National Yang-Ming University, Taipei, 112 and 3Department of Pediatrics, National Taiwan University Hospital, Taipei, 100, Taiwan

Correspondence to: Dr Chen Chang, Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan, R.O.C. E-mail: bmcchen{at}ibms.sinica.edu.tw

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.

Key Words: neuronal activation; high resolution MRI; manganese-enhanced MRI; kainic acid; c-Fos

Abbreviations: BBB, blood-brain barrier; DWI, diffusion-weighted imaging; KA, kainic acid; MEMRI, manganese-enhanced MRI; SI, signal intensity; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging; TLE, temporal lobe epilepsy; VGCC, voltage-gated Ca2+ channel

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Received June 1, 2007. Revised July 31, 2007. Accepted August 6, 2007.


*These authors contributed equally to this work.


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