Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy.
In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.
Costa-Ferro
Zaquer S M
ZS
Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Vitola
Affonso S
AS
Pedroso
Michele F
MF
Cunha
Fernanda B
FB
Xavier
Léder L
LL
Machado
Denise C
DC
Soares
Milena B P
MB
Ribeiro-dos-Santos
Ricardo
R
DaCosta
Jaderson C
JC
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000473:pathology; D066298:In Vitro Techniques; D008094:Lithium; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000601:surgery*; D013997:Time Factors
D015703:Antigens, CD; D005904:Glial Fibrillary Acidic Protein; C485184:enhanced green fluorescent protein; D010862:Pilocarpine; D049452:Green Fluorescent Proteins; D008094:Lithium