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Int J Mol Sci ; 21(12)2020 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-32630606

RESUMEN

Pan-histone deacetylase (HDAC) inhibition with valproic acid (VPA) has beneficial effects after spinal cord injury (SCI), although with side effects. We focused on specific HDAC8 inhibition, because it is known to reduce anti-inflammatory mediators produced by macrophages (Mφ). We hypothesized that HDAC8 inhibition improves functional recovery after SCI by reducing pro-inflammatory classically activated Mφ. Specific HDAC8 inhibition with PCI-34051 reduced the numbers of perilesional Mφ as measured by histological analyses, but did not improve functional recovery (Basso Mouse Scale). We could not reproduce the published improvement of functional recovery described in contusion SCI models using VPA in our T-cut hemisection SCI model. The presence of spared fibers might be the underlying reason for the conflicting data in different SCI models.


Asunto(s)
Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Animales , Antiinflamatorios/farmacología , Ácidos Hidroxámicos/farmacología , Indoles/farmacología , Inflamación/tratamiento farmacológico , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Recuperación de la Función/efectos de los fármacos , Médula Espinal/patología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/inmunología , Ácido Valproico/farmacología
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