Observation of panobinostat alleviates early brain injury in subarachnoid hemorrhage model

Abstract

Objective To observe the effect of panobinostat (LBH589) on the early brain injury (EBI) in the model of subarachnoid hemorrhage(SAH) in SD rats. Methods SD rats were randomly divided into 4 groups: sham(10 rats) and SAH(10 rats), SAH+ vehicle(20 rats) and SAH+ Panobinostat(20 rats). Drug or vehicle was given by lateral-ventricular stereotaxic injection 24h before the SAH model was introduced.Water contents and the neurological scores were determined at 24h post-SAH.The levels of Ac-H3K27 in frontal and lateral lobe were detected by Western blot. Results The mean neurological score of the SAH group was higher than that of the sham group(F=13.000, P=0.007). The water content of the SAH group was higher than that of the sham group (F=8.229, P=0.019). The level of Ac-H3K27 was higher in the SAH+ Panobinostat group than that in the SAH+ vehicle group(F=41.250, P=0.000). The mean neurological score of the SAH+ Panobinostat group was lower than that of the SAH+ vehicle group(F=9.560, P=0.011). The water content of the SAH+ Panobinostat group was lower than that of the SAH+ vehicle group(F=8.211, P=0.020). The correlation analysis indicated that the level of acetylation of H3 was negatively correlated with the neurological score(r=-0.585, P=0.046). Conclusion Panobinostat can improve the neurological behavior and alleviate early brain injury in the SAH model. Key words: Subarachnoid hemorrhage; Brain injury; Panobinostat (LBH589); Histone deacetylase(HDAC)/Enzyme Inhibitor; Neurons; Apoptosis; Acetylation; Animals