The role of BDNF in the adult SVZ has been

The role of BDNF in the adult SVZ has been analyzed by different groups with controversial results. Most studies with BDNF infusions or overexpression in the lateral ventricle demonstrated an increase in the number of newly born neurons in the olfactory bulb. However, Alvarez-Buylla\'s group showed that BDNF did not affect the neurons\' survival in mice while in rats it decreases neuronal survival (for review see Bath et al., 2011). BDNF or its receptors, have also been associated with cell proliferation and neuronal migration (Bath et al., 2011). In the present study, we observed an increase in BDNF expression in the SVZ after the BMMC transplant. Therefore, it would be of interest to analyze if BDNF by itself could be responsible for the effects on proliferation and RGLC differentiation described here. In injuries where the lesion occurs in the white matter, some groups demonstrated that the number of oligodendrocyte precursors in the SVZ increases, and that these cells could be migrating to the lesion area, as was observed with neuroblasts (Menn et al., 2006; Talbott et al., 2005). In our study, we showed white matter damage after BCCL, followed by a reduction in the number of oligodendrocyte progenitors in the SVZ. This contradictory response could be explained by the fact that we submitted the entire SRT 1720 Supplier to a hypoperfusion that is known to affect oligodendrocytes (Farkas et al., 2004; Wakita et al., 2002), differently from the other studies, which induced a localized lesion in the white matter. Models of neonatal hypoperfusion have also shown a reduction in the number of NG2-positive cells, demonstrating how these cells are susceptible to hypoxia (Rothstein and Levison, 2005). After BCCL, we observed a decrease in the number of NG2-positive cells, but the BMMC therapy restored this number. This result indicates that these cells protect the oligodendrocyte progenitors against the injury. The same pattern was observed in the analysis of MBP expression in the optic tract, one of the most affected regions after BCCL. Seven days after ischemia, BCCL animals showed a decrease in the MBP expression, while the animals that were treated with BMMC did not show this reduction. In our model, the factor involved in this event could be the BDNF, which, as discussed above, is expressed more highly after BMMC transplantation. Previous studies have shown that, after spinal-cord lesion, intrathecal delivery of BDNF stimulates myelination and protects the oligodendrocytes from apoptosis (Ikeda et al., 2002; Koda et al., 2002). Also, injection of bone-marrow stem cells overexpressing BDNF reduces demyelination and the number of apoptotic cells in a model of encephalomyelitis (Makar et al., 2008). Therefore, BDNF is probably one of the factors involved in the NG2-cell protection that we observed in the BCCL animals after the BMMC transplantation. In this study, we observed that in animals that suffer global ischemia and receive a BMMC transplant, the number of RGLCs and protection of oligodendrocyte progenitors in the SVZ increase. Although oligodendrocyte progenitors migrate mainly through axon tracts, during development and in some cases of injury it was demonstrated that these progenitors could use radial migration (Diers-Fenger et al., 2001; Suzuki and Goldman, 2003). Further analyses are necessary in order to test the hypothesis based on these indications, suggesting that, in our model, the RGLCs may be acting as a support for the migration of the oligodendrocyte progenitors to the lesion sites, for example the optic tract.
Conclusion The following is the Supplementary data to this article.
Acknowledgments This study was supported by grants from the Ministry of Health (MS/SCTIE/DECIT), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (Inbeb), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). EA is supported by the CNPq, FAPERJ, and Financiadora de Estudos e Projetos (FINEP). We thank Suelen Serio and Felipe Marins for technical assistance.