The beneficial effect of treatment with bone marrow mononuclear cells (BMMCs) was evaluated in different therapeutic windows in a rat model of focal ischemia induced by thermocoagulation of the blood vessels in the left motor, somestesic, and sensorimotor cortices. We also compared the therapeutic benefits between BMMCs and bone marrow-derived mesenchymal stem cells (MSCs). BMMCs and MSCs were obtained from donor rats and injected into the jugular vein after ischemia. BMMCs-treated animals received approximately 3x10(7) cells at post-ischemic days (PIDs) 1, 7, 14, or 30. MSCs-treated animals received approximately 3x10(6) cells at PIDs 1 and 30. Control animals received only the vehicle. The animals were then evaluated for functional sensorimotor recovery weekly with behavioral tests (cylinder test and adhesive test). Significant recovery of sensorimotor function was only observed in the cylinder test in animals treated with BMMCs at PIDs 1 and 7. Similar effects were also observed in the animals treated with MSCs 1 day after ischemia, but not in animals treated with MSCs 30 days after ischemia. Significant decrease in glial scarring did not seem to be a mechanism of action of BMMCs, since treatment with BMMCs did not change the level of expression of GFAP, indicating no significant change in the astrocytic scar in the periphery of the ischemic lesion. These results suggest that BMMCs might be an efficient treatment protocol for stroke only in the acute/subacute phase of the disease, and its efficiency in inducing functional recovery is similar to that of MSCs.

We used the activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) to detect the presence of nitric oxide synthase (NOS) in the developing rat superior colliculus. Our results showed that NOS is present in cells and neuropil in the developing and adult rat superior colliculus. The first NOS-positive cells were detected at postnatal day 7 and were weakly stained. During the following days the number of stained cells increased markedly, reaching a peak by postnatal day 15, coinciding with the time of eye opening in the rat. By the end of the third postnatal week, both the number and intensity of stained cells showed an adult-like pattern. We conclude that NOS expression lags behind the initial period of reorganization of the retinotectal projection. However, NOS activity could be involved in the subsequent synaptic remodeling and plasticity of the retinocollicular projection.

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.