GABAergic Neuronal Precursor Grafting: Implications in Brain Regeneration and Plasticity

Numerous neurological disorders are caused by a dysfunction of the GABAergic system that impairs or either stimulates its inhibitory action over its neuronal targets. Pharmacological drugs have generally been proved very effective in restoring its normal function, but their lack of any sort of spatial or cell type specificity has created some limitations in their use. In the last decades, cell-based therapies using GABAergic neuronal grafts have emerged as a promising treatment, since they may restore the lost equilibrium by cellular replacement of the missing/altered inhibitory neurons or modulating the hyperactive excitatory system. In particular, the discovery that embryonic ganglionic eminence-derived GABAergic precursors are able to disperse and integrate in large areas of the host tissue after grafting has provided a strong rationale for exploiting their use for the treatment of diseased brains. GABAergic neuronal transplantation not only is efficacious to restore normal GABAergic activities but can also trigger or sustain high neuronal plasticity by promoting the general reorganization of local neuronal circuits adding new synaptic connections. These results cast new light on dynamics and plasticity of adult neuronal assemblies and their associated functions disclosing new therapeutic opportunities for the near future.

The role of cell therapy for stroke

Cellular therapy has been evaluated in small animals, subhuman primates, and now humans for the potential repair of brain injury due to stroke. Experimental striate stroke models have proven useful for the purpose of evaluating different treatment paradigms. Early clinical trials involving neuronal transplantation in patients suffering motor-related stroke in the basal ganglia region have begun. This research will be described in this report.