Department of Neurosurgery, University of Health Sciences, Istanbul Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.
Department of Neurosurgery, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey; Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
Injury. 2019 Oct;50(10):1586-1592. doi: 10.1016/j.injury.2019.08.036. Epub 2019 Aug 20.
Traumatic brain injury (TBI) is one of the most common preventable causes of mortality and morbidity. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophysiological mechanisms underlying neuronal loss after TBI. Mildronate is demonstrated to be beneficial in various experimental models of ischemic diseases via anti-inflammatory, antioxidant, and neuroprotective mechanisms. This study aimed to investigate possible antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of mildronate in a rat model of TBI.
A total of 46 male rats were divided into three groups of control, saline-treated TBI, and mildronate-treated TBI. Both TBI groups were subjected to closed-head contusive weight-drop injuries followed by treatment with saline or mildronate (100 mg/kg) administered intraperitoneally. The forebrain was removed 24 h after trauma induction, the activities of myeloperoxidase (MPO) and caspase-3, levels of superoxide dismutase (SOD), luminol- and lucigenin-enhanced chemiluminescence were measured, and histomorphological evaluation of cerebral tissues was performed.
Increased MPO and caspase-3 activities in the vehicle-treated TBI group (p < 0.001) were suppressed in the mildronate-treated TBI group (p < 0.001). Similarly, increase in luminol and lucigenin levels (p < 0.001 and p < 0.01, respectively) in the vehicle-treated TBI group were decreased in the mildronate-treated TBI group (p < 0.001). Concomitantly, in the vehicle-treated TBI group, TBI-induced decrease in SOD activity (p < 0.01) was reversed with mildronate treatment (p < 0.05). On histopathological examination, TBI-induced damage in the cerebral cortex was lesser in the mildronate-treated TBI group than that in other groups.
This study revealed for the first time that mildronate, exhibits neuroprotective effects against TBI because of its anti-inflammatory, antiapoptotic, and antioxidant activities.
创伤性脑损伤（TBI）是最常见的可预防的死亡和发病原因之一。炎症、细胞凋亡、氧化应激和缺血是 TBI 后神经元丢失的一些重要病理生理机制。米屈肼通过抗炎、抗氧化和神经保护机制，已被证明对各种缺血性疾病的实验模型有益。本研究旨在研究米屈肼对 TBI 大鼠模型的可能的抗氧化、抗炎、抗细胞凋亡和神经保护作用。
将 46 只雄性大鼠分为三组：对照组、生理盐水处理的 TBI 组和米屈肼处理的 TBI 组。两组 TBI 大鼠均采用闭合性颅脑撞击伤模型，随后给予腹腔注射生理盐水或米屈肼（100mg/kg）治疗。伤后 24 小时取出大脑，测定髓过氧化物酶（MPO）和半胱天冬酶-3 的活性、超氧化物歧化酶（SOD）的水平、鲁米诺和荧光素增强化学发光，并进行脑组织形态学评价。
与对照组相比，在 TBI 组中，MPO 和半胱天冬酶-3 的活性显著升高（p<0.001），而米屈肼处理的 TBI 组中这些酶的活性显著降低（p<0.001）。同样，在 TBI 组中，鲁米诺和荧光素增强化学发光水平显著升高（p<0.001 和 p<0.01），而米屈肼处理的 TBI 组中这些酶的活性显著降低（p<0.001）。此外，在 TBI 组中，SOD 活性降低（p<0.01），而米屈肼处理的 TBI 组中 SOD 活性升高（p<0.05）。组织病理学检查发现，与其他组相比，米屈肼处理的 TBI 组大脑皮质损伤程度较轻。
本研究首次揭示，米屈肼通过抗炎、抗细胞凋亡和抗氧化作用，对 TBI 具有神经保护作用。
