Regeneration of lesioned entorhino-hippocampal axons in vitro by combined degradation of inhibitory proteoglycans and blockade of Nogo-66/NgR signaling.

Damaged axons do not regenerate after axotomy in the adult mammalian central nervous system (CNS). This may be due to local inhibitory factors at the site of injury, such as overexpression of chondroitin sulfate (CS) proteoglycans (CSPG), and the presence of myelin-associated inhibitors (MAI). To overcome CSPG- or myelin-induced inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For example, NEP1-40 is a synthetic peptide that promotes axonal regeneration by blocking Nogo-66/NgR interaction and chondroitinase ABC (ChABC), which degrades CS, thereby also promoting axon regrowth. Here, we examined whether the combination of these complementary strategies facilitates regeneration of the lesioned entorhino-hippocampal pathway (EHP) in slice cultures. In this model, overexpressed CSPG and MAI impaired axon regrowth, which mimics regeneration failure in vivo. Both CS cleavage with ChABC and NEP1-40 strongly facilitated the regrowth of entorhinal axons after axotomy, permitting the re-establishment of synaptic contacts with target cells. However, the combined treatment did not improve the regeneration induced by ChABC alone, and the delayed treatment of ChABC, but not NEP1-40, had a less pronounced effect on axonal regrowth compared with acute treatment. These results provide insight into the development of new assays and strategies to enhance axon regeneration in injured cortical connections.

Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation.

Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids.

Cultivo de células de Schwann, un modelo de microambiente del sistema nervioso / Schwann cells cultures: a model of the nervous system microenvironment

Algunos aspectos de la fisiopatología del sistema nervioso periférico pueden ser ampliamente estudiados en un modelo celular in vitro, enriquecido en células de Schwann. La célula de Schwann como glia del sistema nervioso periférico produce la mielina responsable de la transmisión saltatoria del impulso, influye en la actividad neural y da soporte y protección axonal. A su vez es blanco de procesos que alteran la normalidad del sistema nervioso periférico como neuropatías congénitas y/o desmielizantes, lesiones nerviosas, respuestas a patógenos neurotrópicos, etc., eventos más frecuentes y discapacitantes en individuos adultos. de ahí la importancia de obtener célulkas a partir de animales adultos. Sin embargo, estas células son mitóticamente lentas y su obtención en cultico requiere de condiciones específicas que estimulen su proliferación y actividad. describimos a continuación, un modelo in vitro mediante el cual se obtienen cultivos enriquecidos en céelulas de Schwann de ratón adulto, las cuales conservan características de las células in vivo, lo cual permite estudiar diversos fenómenos específicos del sistema nervioso períferico