ABSTRACT
Emerging literature suggests that after a stroke, the peri-infarct region exhibits dynamic changes in excitability. In rodent stroke models, treatments that enhance excitability in the peri-infarct cerebral cortex promote motor recovery. This increase in cortical excitability and plasticity is opposed by increases in tonic GABAergic inhibition in the peri-infarct zone beginning three days after a stroke in a mouse model. Maintenance of a favorable excitatory-inhibitory balance promoting cerebrocortical excitability could potentially improve recovery. Brevetoxin-2 (PbTx-2) is a voltage-gated sodium channel (VGSC) gating modifier that increases intracellular sodium ([Na+]i), upregulates N-methyl-D-aspartate receptor (NMDAR) channel activity and engages downstream calcium (Ca2+) signaling pathways. In immature cerebrocortical neurons, PbTx-2 promoted neuronal structural plasticity by increasing neurite outgrowth, dendritogenesis and synaptogenesis. We hypothesized that PbTx-2 may promote excitability and structural remodeling in the peri-infarct region, leading to improved functional outcomes following a stroke. We tested this hypothesis using epicortical application of PbTx-2 after a photothrombotic stroke in mice. We show that PbTx-2 enhanced the dendritic arborization and synapse density of cortical layer V pyramidal neurons in the peri-infarct cortex. PbTx-2 also produced a robust improvement of motor recovery. These results suggest a novel pharmacologic approach to mimic activity-dependent recovery from stroke.
Subject(s)
Cerebral Cortex/drug effects , Excitatory Amino Acid Agonists/administration & dosage , Marine Toxins/administration & dosage , Motor Activity/drug effects , Neuronal Plasticity/drug effects , Oxocins/administration & dosage , Thrombotic Stroke/drug therapy , Animals , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Disease Models, Animal , Injections , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice, Transgenic , Recovery of Function , Thrombotic Stroke/metabolism , Thrombotic Stroke/pathology , Thrombotic Stroke/physiopathologyABSTRACT
Os oitos milhões de brasileiros com mais 65 anos padecem da falta de políticas de saúde pública adequadas e atendimento especializado. As vésperas da celebração de mais um Dia Nacional do Idoso (27 de setembro), os 8.489.958 brasileiros, inseridos nesta faixa etária, que correspondem a 5,85 por cento da população nacional segundo o censo demográfico do IBGE de 2000, ainda encontram poucos motivos para comemorar a data
