Abstract|Motor Neuron Disease 1| Volume 357, SUPPLEMENT 1, e50, October 15, 2015

Rehabilitation of blood-spinal cord-barrier toward amyotrophic lateral sclerosis therapy

      Background: ALS patients and transgenic mice expressing ALS-associated superoxide dismutase 1 (SOD1) mutations show alterations in the blood-spinal cord barrier (B-SC-B) as suggested from the reduction of levels of various tight junction proteins (TJPs) including zonula occludens-1 (ZO-1), occludin and claudin-5 between endothelial cells and early protection of the B-SC-B integrity was found to delay onset of motor-neuron impairment and degeneration.
      Objective: The aim of this research was to investigate if inhibition of the axis CXCL12/CXCR4 receptor widely expressed in neurons and glial cells and modulates neuronal apoptosis, may improve motor neurons survival by increasing the expression of tight junction proteins and rehabilitation of the barrier.
      Materials and methods: Transgenic mice model of ALS were treated with AMD3100, antagonist of CXCR4. Motor function, weight changes and survival were evaluated. In a separate experiment, mice were sacrificed after one month of treatment and levels of proteins essential for the formation of the barrier in comparison with proteins that do not participate in the barrier were measured.
      Results: We found that chronic administration of AMD3100 to ALS mouse model was effective in restoring the expression of tight junction proteins and considerably increase the survival, confirming the importance of early treatment for rehabilitation of the barriers to prevent infiltration of neurotoxic products and microhemorrhages.
      Conclusions: These data reveal that multi-faceted action of AMD3100 may provide a novel option for ALS therapy leading to rehabilitation of B-SC-B proteins and thus preventing additional damage to motor neurons.