Programa de Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Ciudad de México, Mexico.
Dirección de Investigación, Arenal de Guadalupe, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, SSa, Calzada México-Xochimilco 289, Arenal de Guadalupe, Ciudad de México, Mexico.
Neurochem Res. 2024 Nov;49(11):3043-3059. doi: 10.1007/s11064-024-04222-9. Epub 2024 Aug 6.
Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.
去甲肾上腺素(NA)水平在皮质损伤后的头几个小时和几天内发生改变。NA 调节运动功能的恢复。本研究调查了铁诱导的皮质损伤是否会调节大脑皮质、脑桥和小脑的去甲肾上腺素合成和多巴胺β-羟化酶(DBH)活性,以应对大脑的氧化应激。78 只大鼠分为两组:(a)假手术组,接受皮质内注射载体溶液;(b)损伤组,接受皮质内注射氯化亚铁。损伤后 20 天评估运动缺陷。第 3 天和第 20 天,处死大鼠测量氧化应激指标(活性氧(ROS)、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG))和儿茶酚胺(NA、多巴胺(DA)),以及 DBH mRNA 和蛋白水平。我们的结果表明,铁诱导的皮质损伤会在损伤后 3 天增加大脑皮质、脑桥和小脑的去甲肾上腺素合成和 DBH 活性,主要发生在损伤侧,以应对氧化应激。在对侧观察到去甲肾上腺素活性的代偿性增加,但小脑和脑桥的 DBH mRNA 和蛋白水平没有变化。总之,铁诱导的皮质损伤增加了大脑皮质、脑桥和小脑的去甲肾上腺素反应,特别是在损伤侧,伴有对侧的代偿反应。抗氧化活性对抗氧化应激,有利于运动缺陷后的功能恢复。