Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats.
Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and beta galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-beta gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.
Chu
Kon
K
Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Kim
Manho
M
Jung
Keun-Hwa
KH
Jeon
Daejong
D
Lee
Soon-Tae
ST
Kim
Juhyun
J
Jeong
Sang-Wuk
SW
Kim
Seung Up
SU
Lee
Sang Kun
SK
Shin
Hee-Sup
HS
Roh
Jae-Kyu
JK
D000374:Aggression / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D010320:Parvalbumins / Q000378:metabolism; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D012640:Seizures / Q000209:etiology / Q000628:therapy*; D013226:Status Epilepticus / Q000139:chemically induced / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D010320:Parvalbumins; D018091:Receptors, AMPA; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; C104722:glutamate receptor ionotropic, AMPA 2