Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy

• Published in: Epilepsia (Copenhagen) 2012-07, Vol.53 (7), p.1225-1232
• Main Authors: Malheiros, Jackeline M., Polli, Roberson S., Paiva, Fernando F., Longo, Beatriz M., Mello, Luiz E., Silva, Afonso C., Tannús, Alberto, Covolan, Luciene
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Biological and medical sciences; Cycloheximide; Cycloheximide - administration & dosage; Dentate gyrus; Disease Models, Animal; Drug Interactions; Drug therapy; Epilepsy; Epilepsy - chemically induced; Epilepsy - drug therapy; Epilepsy - pathology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - drug effects; Hippocampus - pathology; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Manganese; Medical sciences; Mossy fiber sprouting; mossy fibers; Mossy Fibers, Hippocampal - drug effects; Mossy Fibers, Hippocampal - pathology; Muscarinic Agonists - toxicity; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Pilocarpine; Pilocarpine - toxicity; Protein Synthesis Inhibitors - administration & dosage; Rats; Rats, Wistar; Statistics, Nonparametric; Temporal lobe; Thiopental - pharmacology; Thiopental - therapeutic use; Zinc
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2012.03521.x

Summary 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