Abstract
Status epilepticus (SE) is a condition of persistent seizure that leads to brain damage and, frequently, to the establishment of chronic epilepsy. Cord blood is an important source of adult stem cells for the treatment of neurological disorders. The present study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (HUCBC) transplanted into rats after induction of SE by the administration of lithium and pilocarpine chloride. Transplantation of HUCBC into epileptic rats protected against neuronal loss in the hippocampal subfields CA1, CA3 and in the hilus of the dentate gyrus, up to 300 days after SE induction. Moreover, transplanted rats had reduced frequency and duration of spontaneous recurrent seizures (SRS) 15, 120 and 300 days after the SE. Our study shows that HUCBC provide prominent antiepileptic and neuroprotective effects in the experimental model of epilepsy and reinforces that early interventions can protect the brain against the establishment of epilepsy.
References
Abercrombie M (1946) The density of neurones in the human hippocampus. Anat Rec 94:239–247
Arien-Zakay H, Lecht S, Nagler A, Lazarovici P (2011) Neuroprotection by human umbilical cord bloodderived progenitors in ischemic brain injuries. Arch Ital Biol 149:233–245
Costa-Ferro ZS, Vitola AS, Pedroso MF, Cunha FB, Xavier LL, Machado DC, Soares MB, Ribeiro-dos-Santos R, DaCosta JC (2010) Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy. Seizure 19:84–92
Costa-Ferro ZS, Souza BS, Leal MM, Kaneto CM, Azevedo CM, da Silva IC, Soares MB, Ribeiro-dos-Santos R, Dacosta JC (2012) Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats. Neurobiol Dis 46:302–313
Erices A, Conget P, Minguel JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242
Garbuzova-Davis S, Willing AE, Zigova T, Saporta S, Justen EB, Lane JC, Hudson JE, Chen N, Davis CD, Sanberg PR (2003) Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J. Hematother. Stem Cell Res 12:255–270
Löscher W, Brandt C (2010) Prevention or Modification of Epileptogenesis after Brain Insults: experimental approaches and translational research. Pharmacol Rev 62:668–700
Lu L, Shen RN, Broxmeyer HE (1996) Stem cells from bone marrow, umbilical cord blood and peripheral blood for clinical application: current status and future application. Crit Rev Oncol Hematol 22:61–78
Newcomb JD, Ajmo CTJ, Sanberg CD, Sanberg PR, Pennypacker KR, Willing AE (2006) Timing of cord blood treatment after experimental stroke determines therapeutic efficacy. Cell Transplant 15:213–223
Nieda M, Nicol A, Denning-Kendall P, Sweetenham J, Bradley B, Hows J (1997) Endothelial cell precursors are normal components of human umbilical cord blood. Br J Haematol 98:775–777
Paradiso B, Zucchini S, Su T, Bovolenta R, Berto E, Marconi P, Marzola A, Navarro Mora G, Fabene PF, Simonato M (2011) Localized overexpression of FGF-2 and BDNF in hippocampus reduces mossy fiber sprouting and spontaneous seizures up to 4 weeks after pilocarpine-induced status epilepticus. Epilepsia 52:572–578
Park DH, Lee JH, Borlongan CV, Sanberg PR, Chung YG, Cho TH (2011) Transplantation of umbilical cord blood stem cells for treating spinal cord injury. Stem Cell Rev 7:181–194
Paxinos G, Watson C (1996) The rat brain in stereotaxic coordinates, compact 3rd edition CDRom. Academic Press, San Diego
Racine RJ (1972) Modification of seizure activity by electrical stimulation I. After-discharge threshold. Electroencephalogra Clin Neurophysiol 32:269–279
Simonato M, Zucchini S (2010) Are the neurotrophic factors a suitable therapeutic target for the prevention of epileptogenesis? Epilepsia 51:48–51
Turski L, Ikonomidou C, Turski WA, Bortolotto ZA, Cavalheiro EA (1989) Cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse 3:154–171
Vendrame M, Gemma C, de Mesquita D, Collier L, Bickford PC, Sanberg CD, Sanberg PR, Pennypacker KR, Willing AE (2005) Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev 14:595–604
Venturin GT, Greggio S, Marinowic DR, Zanirati G, Cammarota M, Machado DC, DaCosta JC (2011) Bone marrow mononuclear cells reduce seizure frequency and improve cognitive outcome in chronic epileptic rats. Life Sci 89:229–234
Vezzani A, Friedman A (2011) Brain inflammation as a biomarker in epilepsy. Biomark Med 5:607–614
Vezzani A, Aronica E, Mazarati A, Pittman QJ (2011) Epilepsy and brain inflammation. Exp Neurol doi:10.1016/j.expneurol.2011.09.033
Uccelli A (2013) Mesenchymal stem cells exert a remarkable regenerative effect requiring minimal CNS integration. Commentary on: “Mesenchymal stem cells protect CNS neurons against glutamate excitotoxicity by inhibiting glutamate receptor expression and function” by Voulgari-Kokota et al. Exp Neurol doi:10.1016/j.expneurol.2013.01.028
Acknowledgments
This work was supported by the Brazilian National Research Council (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) and Financiadora de Estudos e Projetos (FINEP). The authors would like to thank Geraldo Pedral for assistance with flow cytometry analysis.
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Costa-Ferro, Z.S.M., de Borba Cunha, F., de Freitas Souza, B.S. et al. Antiepileptic and neuroprotective effects of human umbilical cord blood mononuclear cells in a pilocarpine-induced epilepsy model. Cytotechnology 66, 193–199 (2014). https://doi.org/10.1007/s10616-013-9557-3
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DOI: https://doi.org/10.1007/s10616-013-9557-3