ABSTRACT
OBJECTIVE@#To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism.@*METHODS@#Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum.@*RESULTS@#After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05).@*CONCLUSION@#Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.
Subject(s)
Animals , Male , Rats , Autophagy , Chromatin , Curcumin/pharmacology , Mammals , Manganese/toxicity , Rats, Sprague-Dawley , Saline Solution/pharmacology , TOR Serine-Threonine KinasesABSTRACT
JUSTIFICATIVA E OBJETIVOS: É necessário proceder a relaxamento cerebral durante cirurgia intracraniana e a terapia hiperosmolar é uma das medidas para sua produção. Com frequência, pacientes neurocirúrgicos apresentam distúrbios de sódio. O objetivo deste trabalho foi quantificar e determinar o relaxamento cerebral e a duração das alterações hidroeletrólíticas decorrentes do uso do manitol versus solução isoncótica hipertônica (SIH) durante neurocirurgia. MÉTODO: Foram avaliados relaxamento cerebral e alterações hidroeletrolíticas de 29 pacientes adultos antes, 30 e 120 minutos após o término da infusão de carga aproximadamente equiosmolar de manitol 20 por cento (250 mL) ou SIH (120 mL). Registraram-se volume de líquidos intravenosos infundidos e diurese. Considerou-se p < 0,05 como significativo. RESULTADOS: Não houve diferença estatística significativa entre os dois grupos quanto ao relaxamento cerebral. Embora várias diferenças nos eletrólitos e no equilíbrio ácido-básico com o uso de manitol ou SIH tenham alcançado significância estatística, apenas a redução do sódio plasmático, 30 minutos após o uso do manitol, em média de 6,42 ± 0,40 mEq.L-1 e a elevação do cloro em média 5,41 ± 0,96 mEq.L-1 e 5,45 ± 1,45 mEq.L-1, 30 e 120 minutos, respectivamente, após a SIH deslocaram transitoriamente os níveis séricos desses íons da faixa de normalidade laboratorial. O grupo do manitol (20 por cento) apresentou diurese significativamente maior nos dois tempos estudados em comparação com o grupo da SIH. CONCLUSÕES: Solução salina isoncótica hipertônica [NaCl 7,2 por cento/HES (200/0,5) 6 por cento] e manitol (20 por cento), em dose única com cargas osmolares equivalentes, foram efetivos e seguros em produzir relaxamento cerebral durante os procedimentos neurocirúrgicos eletivos sob anestesia geral.
BACKGROUND AND OBJECTIVE: Cerebral relaxation during intracranial surgery is necessary, and hiperosmolar therapy is one of the measures used to this end. Frequently, neurosurgical patients have sodium imbalances. The objective of the present study was to quantify and determine cerebral relaxation and duration of hydroelectrolytic changes secondary to the use of mannitol versus hypertonic isoncotic solution (HIS) during neurosurgery. METHODS: Cerebral relaxation and hydroelectrolytic changes were evaluated in 29 adult patients before de beginning of infusion, and 30 and 120 minutes after the infusion of equiosmolar loads of approximately 20 percent mannitol (250 mL) or HIS (120 mL). The volume of intravenous fluids infused and diuresis were recorded. A p < 0.05 was considered significant. RESULTS: A statistically significant difference in cerebral relaxation between both groups was not observed. Although several changes in electrolyte levels and acid-base balance with mannitol or HIS reached statistical significance only the reduction in plasma sodium 30 minutes after infusion of mannitol, mean of 6.42 ± 0.40 mEq.L-1, and the increase in chloride, mean of 5.41 ± 0.96 mEq.L-1 and 5.45 ± 1.45 mEq.L-1 30 and 120 minutes after infusion of HIS, caused a transitory dislocation of serum ion levels from normal range. The mannitol (20 percent) group had a significantly greater diuresis at both times studied compared with HIS group. CONCLUSIONS: A single dose of hypertonic isoncotic saline solution [7.2 percent NaCl/6 percent HES (200/0.5)] and mannitol (20 percent) with equivalent osmolar loads were effective and safe in producing cerebral relaxation during elective neurosurgical procedures under general anesthesia.
JUSTIFICATIVA Y OBJETIVOS: La relajación cerebral es necesaria durante la cirugía intracraneana, y la terapia hiperosmolar es una de las medidas para su producción. Los pacientes neuroquirúrgicos a menudo presentan disturbios del sodio. El objetivo del trabajo fue cuantificar y determinar la relajación cerebral y la duración de las alteraciones hidroelectrolíticas provenientes del uso del manitol versus solución isoncótica hipertónica (SIH), durante la neurocirugía. MÉTODO: Se evaluaron la relajación cerebral y las alteraciones hidroelectrolíticas de 29 pacientes adultos antes, 30 y 120 min después del término de la infusión de carga aproximadamente equiosmolar de manitol 20 por ciento (250 mL) o SIH (120 mL). Se registró el volumen de los líquidos intravenosos infundidos y la diuresis. El P < 0,05 fue considerado significativo. RESULTADOS: No hubo ninguna diferencia estadística significativa entre los dos grupos en cuanto a la relajación cerebral. Aunque varias diferencias en los electrólitos y el equilibrio ácido-básico con el uso de manitol o SIH, hayan alcanzado una significancia estadística, solamente la reducción del sodio plasmático 30 min después del uso del manitol, como promedio de 6,42 ± 0,40 mEq.L-1, y la elevación del cloro como promedio 5,41 ± 0,96 mEq.L-1 y 5,45 ± 1,45 mEq.L-1, 30 y 120 min respectivamente después de la SIH, alteraron transitoriamente los niveles séricos de esos iones del rango de la normalidad laboratorial. El grupo del manitol (20 por ciento) tuvo una diuresis significativamente mayor en los dos tiempos estudiados en comparación con el grupo de la SIH. CONCLUSIONES: La solución salina isoncótica-hipertónica [NaCl 7,2 por ciento/HES (200/0,5) 6 por ciento] y manitol (20 por ciento), en dosis única con carga osmolar equivalente, fueron efectivos y seguros para generar la relajación cerebral durante los procedimientos neuroquirúrgicos electivos bajo la anestesia general.