**6. Conclusion**

*Neuroprotection - New Approaches and Prospects*

Both growth factors and IL-10 have been reported to be directly involved in the stimulation of SVZ and SGZ stem cells; specifically, IL-10 has been observed to induce stem cell proliferation but not differentiation in primary cultures [84]. Moreover, IL-10 has immunomodulatory capacity as it inhibits the synthesis and release of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β that are known to affect neurogenesis [85]. Moreover, growth factors such as NT-3 maintain viable stem cells from neurogenic niches facilitating plasticity [86]. BDNF promotes the proliferation and survival of neuroblasts [87] and IGF-1 promotes stem cell differentiation and migration of neuroblasts [88]. Therefore, this investigation allowed to demonstrate that Cop-1 is capable of raising the expression of IL-10 and growth

*Effect of the copolymer-1 on the expression of growth factors and IL-10. Gene expression of: (A) BDNF; (B) NT-3; (C) IGF-1; and (D) IL-10. Bars represent mean ± SEM of 5 rats from each group. \*p < 0.05,* 

In order to know if Cop-1 modulates the number of leukocytes in CP and to know if these intervene in the synthesis and release of growth factors and IL-10, we evaluated the cell types present in the cerebrospinal fluid in animals submitted to tMCAO and Cop-1 therapy. The results showed a significant increment in CD8+ T cells, which positively linked with the increase in growth factors and IL-10 [unpublished data]. The increase in CD8+ T lymphocytes has been observed as an effect of copaxone immunization in patients with MS [46]. In addition, experiments performed in the EAE model have considered these cells indispensable for the development of the beneficial effect of Cop-1 [89]. However, it is necessary to identify the nature of these cells and whether the type of CD8 T lymphocytes is of a regulatory phenotype. Finally, the combination of Cop-1 with other strategies like polyunsaturated fatty acids has shown optimistic results as together, they have a greater capacity to significantly reduce the size of the infarction in the tMCAO model [unpublished data].

factors, which have beneficial effects on neurogenesis.

*\*\*p < 0.001. Mann-Whitney U test. Dunn's post hoc multiple comparison test.*

**150**

**Figure 3.**

The existing evidence of the effect of Cop-1 in the tMCAO model has been very encouraging, as it shows a significant neurological recovery. This beneficial effect could be caused by modulatory mechanisms that allow the increase of IL-4 and the reduction of TNF-α and IL-1β at the lesion site, promoting then neuroprotection. Additionally, neurological recovery could also be reinforced by the changes induced by Cop-1 at the CP as the increase of IL-10 and growth factors in this site stimulate neurogenesis after ischemia. We consider that more investigations are needed in order to analyze in greater detail the mechanism by which Cop-1 acts so that in the medium term, it may be considered as a pharmacological alternative for patients suffering from a cerebrovascular event.
