PMID- 25157845 OWN - NLM STAT- MEDLINE DCOM- 20151209 LR - 20240322 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 8 DP - 2014 TI - Influence of delivery method on neuroprotection by bone marrow mononuclear cell therapy following ventral root reimplantation with fibrin sealant. PG - e105712 LID - 10.1371/journal.pone.0105712 [doi] LID - e105712 AB - The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results. FAU - Barbizan, Roberta AU - Barbizan R AD - Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil. FAU - Castro, Mateus V AU - Castro MV AD - Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil. FAU - Barraviera, Benedito AU - Barraviera B AD - Center for the Study of Venoms and Venomous Animals (CEVAP), Sao Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, Sao Paulo, Brazil. FAU - Ferreira, Rui S Jr AU - Ferreira RS Jr AD - Center for the Study of Venoms and Venomous Animals (CEVAP), Sao Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, Sao Paulo, Brazil. FAU - Oliveira, Alexandre L R AU - Oliveira AL AD - Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140826 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Fibrin Tissue Adhesive) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cranial Nerve Injuries MH - Female MH - Fibrin Tissue Adhesive/*therapeutic use MH - Gene Expression MH - Glial Cell Line-Derived Neurotrophic Factor/genetics/metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Leukocytes, Mononuclear/*transplantation MH - Microglia/physiology MH - Nerve Tissue/transplantation MH - Rats, Inbred Lew MH - Recovery of Function MH - Spinal Nerve Roots/pathology PMC - PMC4144952 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/08/27 06:00 MHDA- 2015/12/15 06:00 PMCR- 2014/08/26 CRDT- 2014/08/27 06:00 PHST- 2014/06/08 00:00 [received] PHST- 2014/07/23 00:00 [accepted] PHST- 2014/08/27 06:00 [entrez] PHST- 2014/08/27 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2014/08/26 00:00 [pmc-release] AID - PONE-D-14-25581 [pii] AID - 10.1371/journal.pone.0105712 [doi] PST - epublish SO - PLoS One. 2014 Aug 26;9(8):e105712. doi: 10.1371/journal.pone.0105712. eCollection 2014.