Plasticidade sináptica e sobrevivência neuronal após avulsão de raízes motoras e tratamento com células tronco mesenquimais

Abstract

The ventral root avulsion, in the interface of the central and peripheral nervous system, promotes a significant synaptic loss with degeneration up to 80% of the affected motoneurons. Until the present moment, there are not effective strategies that propitiate a reversion or assuage this clinical. Recent studies attribute a neuroprotective potential of mesenchymal stem cells (MSC) to the production of neurotrophic factors. However, little is known about the impact of this treatment in the neuronal survival and synaptic plasticity in the central nervous system (CNS). With the intention of investigating processes related with this treatment, the present study proposed the analysis of the survival of medullary motoneurons in rats subjected to the ventral root avulsion, after therapy using MSC, in the acute (2 weeks) and chronic (6 weeks) periods after the lesion. An analysis of the synaptic inputs dynamics and the astroglial reaction was accomplished. In order to identify conditions to promote the survival and regeneration of axotomized motoneurons, the production of RNA for neurotrophic factors (BDNF and GDNF) was determined in vitro and in vivo, as well as the detection of these proteins in vivo. Thus, it was observed that the treatment with MSC promoted a significant neuroprotective effect on the harmed motoneurons and consequent increase of the neuronal survival in the acute and chronic periods after the lesion. Such protection could be attributed to the local production of BDNF and GDNF by MSC andfor their action on resident cells of CNS. The presence of MSC in the spinal cord microenvironment promoted synaptic stabilization, reduction of the glial reaction, what transcended a need for differentiation in neurons or glia, once these assured a local synthesis of the neurotrophic factors.