4.7 Article

Transplantation of Bone Marrow Mononuclear Cells Modulates Hippocampal Expression of Growth Factors in Chronically Epileptic Animals

Journal

CNS NEUROSCIENCE & THERAPEUTICS
Volume 21, Issue 5, Pages 463-471

Publisher

WILEY
DOI: 10.1111/cns.12382

Keywords

Epilepsy; Neurotrophic factors; Pilocarpine; Stem cells

Funding

  1. Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [PQG-11/1546-1, ARD- 11/1678-0]
  2. Pandurata Ltda
  3. Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES)

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AimsIn previous studies, transplantation of bone marrow mononuclear cells (BMMCs) in epileptic animals has been found to be neuroprotective. However, the mechanism by which the BMMCs act remains unclear. We hypothesize that BMMCs may provide neuroprotection to the epileptic brain through trophic support. To test our hypothesis, we studied the temporal expression of neurotrophins after BMMC transplantation in the epileptic rat hippocampus. MethodsChronically epileptic rats were intravenously transplanted with 1x10(7) BMMCs isolated from GFP transgenic mice. Expression levels of BDNF, GDNF, NGF, VEGF, and TGF-1, and their receptors, were evaluated by ELISA and/or qRT-PCR analysis. ResultsOur data revealed increased protein expression of BDNF, GDNF, NGF, and VEGF and reduced levels of TGF-1 in the hippocampus of transplanted epileptic animals. Additionally, an increase in the mRNA expression of BDNF, GDNF, and VEGF, a reduction in TGF-1, and a decrease in mRNA levels of the TrkA and TGFR-1 receptors were also observed. ConclusionThe gain provided by transplanted BMMCs in the epileptic brain may be related to the ability of these cells in modulating the network of neurotrophins and angiogenic signals.

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