GABAergic imbalance is normalized by dopamine D1 receptor activation in the striatum contralateral to the cortical injury in motor deficit-recovered rats.

RATIONALE: The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function, which may be modulated by dopamine. OBJECTIVES: We studied whether the activation of dopamine D1 receptors (D1Rs) modulates the γ-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury. METHODS: The D1R agonist SKF-38393 (0, 2, 3, or 4 mg/kg) was administered at 24, 48, 96, and 192 h post-injury, and then rats were decapitated to determine GABA and glutamate levels and the levels of D1R mRNA on both sides of the striatum. RESULTS: GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D1R agonist, but this treatment did not produce a significant effect on glutamate levels, suggesting that glutamate was metabolized into GABA. The administration of SKF-38393 (2 mg/kg) decreased the levels of D1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D1R agonist increased the D1R mRNA levels, an effect that was blocked by SCH-23390. CONCLUSION: The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal D1R activation, and the D1R agonist-induced increases in the D1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.

Treatment with bone marrow mononuclear cells induces functional recovery and decreases neurodegeneration after sensorimotor cortical ischemia in rats.

We evaluated the beneficial effect of treatment with bone marrow mononuclear cells(BMMC) in a rat model of focal ischemia induced by thermocoagulation of the blood vessels in the left sensorimotor cortex. BMMC were obtained from donor rats and injected into the femoral vein one day after ischemia. BMMC-treated animals received approx. 3×107 cells and control animals received PBS. Animals were evaluated for functional sensorimotor recovery weekly with behavioral tests and for changes in neurodegeneration and structural plasticity with histochemical and immunostaining techniques, respectively. The BMMC-treated group showed a significant recovery of function in the cylinder test 14, 21 and 28 days after ischemia. In the beam test, both groups showed improvement, with a tendency for faster recovery in the BMMC-treated group. In the adhesive test, both groups did not show significant recovery of function. FJC+ cell counting revealed significant decrease in the neurodegeneration in the periphery of the lesion in the BMMC-treated group. The analyses by immunoblotting revealed no significant difference in the expression of GAP-43 and synaptophysin between the groups. Thus, our results showed beneficial effects of the treatment with BMMC, which promoted significant functional recovery and decreased neurodegeneration. These results suggest that the therapy with BMMC is effective and might be a protocol of treatment for stroke in humans, alternative to the therapy proposed with the bone marrow-derived mesenchymal stem cells.