The use of bone marrow mononuclear cells (BMMCs) has been shown as a putative efficient therapy for stroke. However, the mechanisms of therapeutic action are not yet completely known. Mannose receptor (MR) is a subgroup of the C-type lectin receptor superfamily involved in innate immune response in several tissues. Although known primarily for its immune function, MR also has important roles in cell migration, cell debris clearance and tissue remodeling during inflammation and wound healing. Here we analyzed MR expression in brains of rats one week after induction of unilateral focal cortical ischemia by thermocoagulation in blood vessels of sensorimotor cortex. Additionally, we evaluated possible changes in such expression in cortices of rats subjected to ischemia plus treatment with BMMCs. Our results showed high expression of MR in an unknown GFAP(+) cell type and in phagocytic macrophages/microglia within the lesion boundary zone whereas in the non-injured (contralateral) cortical parenchyma, low levels of MR expression were observed. Moreover, therapy with BMMCs induced overexpression of MR in ipsilateral (injured) cortex. Previous studies from our group have shown functional recovery and decreased neurodegeneration in BMMC-treated rats in the same model of focal cortical ischemia. Thus, we suggest that ischemic injury induces large increase in MR expression as part of a mechanism for clearance of damage-associated molecular patterns (DAMPs). In addition, induction of MR overexpression by BMMCs might increase the efficiency of clearance, being one of the protective mechanisms of these cells.

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BackgroundDifferent models of cortical lesion lead to different effects on plasticity of connections and loss of function. In opposition to ischemia, cortical lesion made by ablation does not induce significant adaptive plasticity of corticocortical and corticostriatal projections and leads to functional alterations other than those observed after ischemia. We have demonstrated sensorimotor recovery after treatment with bone marrow-derived mesenchymal stem cells (MSCs) or bone marrow mononuclear cells (BMMCs) in a model of focal cortical ischemia. Here, we extended this analysis evaluating the effect of these cells on sensorimotor recovery after focal cortical ablation, reproducing the same size and location of previous ischemic lesion.FindingsFocal cerebral aspiration of the six cortical layers in left frontoparietal cortex was performed in male Wistar rats. One day later, MSCs or BMMCs were administrated (i.v.) in the ablated animals. Vehicle was administrated in the control group. Sensorimotor tests were performed before and after injury followed by i.v. injection. The monitoring of functional recovery was performed weekly during three post-ablation months. The results showed significant sensorimotor recovery with both treatments, whereas control groups had no recovery. Moreover, both cell types induced the same level of recovery.ConclusionsBone marrow cells showed therapeutic efficacy in a model of brain injury known to promote low structural plasticity. Thus, the results support the idea of BMMCs as better candidates to treat acute CNS injuries than MSCs, since they have the same therapeutic potential, but its obtainment for autologous transplantation has been shown to be faster and easier.

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