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


RESULTS
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.


CONCLUSIONS
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.
Department of Physiology, Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil.
Jackeline M
JM
Malheiros
Roberson S
RS
Polli
Fernando F
FF
Paiva
Beatriz M
BM
Longo
Luiz E
LE
Mello
Afonso C
AC
Silva
Alberto
A
Tannús
Luciene
L
Covolan
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D003513:Cycloheximide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects* / Q000473:pathology; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013874:Thiopental / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D018721:Muscarinic Agonists; D011500:Protein Synthesis Inhibitors; D010862:Pilocarpine; D008345:Manganese; D003513:Cycloheximide; D013874:Thiopental