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Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy
Authors:Malheiros Jackeline M  Polli Roberson S  Paiva Fernando F  Longo Beatriz M  Mello Luiz E  Silva Afonso C  Tannús Alberto  Covolan Luciene
Institution:1. Department of Physiology, Universidade Federal de S?o Paulo – UNIFESP, S?o Paulo, Brazil;2. CIERMag‐S?o Carlos Institute of Physics, University of S?o Paulo, S?o Carlos, Brazil;3. Cerebral Microcirculation Unit/Laboratory of Functional and Molecular Imaging/National Institute of Neurological Disorders and Stroke/National Institutes of Health, Bethesda, Maryland, U.S.A.
Abstract:Purpose: Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese‐enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well‐established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE). Methods: To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was coadministered with Pilo in a subgroup of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo‐Timm histologic labeling of zinc mossy fiber terminals in the dentate gyrus (DG). Key Findings: Chronically epileptic rats displaying MFS as detected by neo‐Timm histology had a hyperintense MEMRI signal in the DG, whereas chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to nonepileptic control animals. A strong correlation (r = 0.81, p < 0.001) was found between MEMRI signal enhancement and MFS. Significance: This study shows that MEMRI is an attractive noninvasive method for detection of mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy.
Keywords:Mossy fiber sprouting  Epilepsy  Pilocarpine  Magnetic resonance imaging  Manganese  Animal models
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