Erythropoietin reduces epileptogenic processes following status epilepticus.
OBJECTIVE
Erythropoietin (EPO) has neuron and astroglial protective effects via reduction of tissue-injuring molecules such as reactive oxygen species, glutamate, inflammatory cytokines, and other damaging molecules. Although EPO may constitute an effective therapeutic modality in cases of epileptic insult, no study has been performed on the effects of exogenous EPO on the chronic seizure formation. In this study, we attempted to investigate if EPO could modulate the altered microenvironment in the epileptic rat brain.


METHODS
Morphological changes in the hippocampi of rats subjected to lithium-pilocarpine-induced status epilepticus (SE) were examined with respect to neuronal loss, inflammation, blood-brain barrier (BBB) leakage, and cell genesis. Spontaneous recurrent seizures (SRSs) were investigated by long-term video-EEG monitoring.


RESULTS
EPO receptor (EPOR) was found to be increased in the hippocampus after SE. Administered EPO prevented, during the latent period following SE, BBB leakage, neuronal death, and microglia activation in the dentate hilus, CA1, and CA3, and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1. Moreover, EPO reduced the risk of SRS development.


CONCLUSIONS
These findings suggest that EPO has a potential therapeutic role in the setting of acute epileptic insults.
Chu
Kon
K
Stroke & Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Jung
Keun-Hwa
KH
Lee
Soon-Tae
ST
Kim
Jin-Hee
JH
Kang
Kyung-Muk
KM
Kim
Hyun-Kyung
HK
Lim
Jae-Sung
JS
Park
Hee-Kwon
HK
Kim
Manho
M
Lee
Sang Kun
SK
Roh
Jae-Kyu
JK
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004921:Erythropoietin / Q000627:therapeutic use*; D019793:Fluorescein; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D039481:CD11b Antigen; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D010862:Pilocarpine; D004921:Erythropoietin; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D019793:Fluorescein