Songarj Phuriphong, Luh Clara, Staib-Lasarzik Irina, Engelhard Kristin, Moosmann Bernd, Thal Serge C
Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Neurosci Lett. 2015 Jan 1;584:253-8. doi: 10.1016/j.neulet.2014.10.037. Epub 2014 Oct 28.
Oxidative stress due to free radical formation is an important mechanism of secondary brain damage following traumatic brain injury (TBI). Phenothiazine has been found to be a strong antioxidant in eukaryotic cells in vitro and in invertebrates in vivo. The present study was designed to determine the neuroprotective potency of unsubstituted phenothiazine in a paradigm of acute brain injury. Thirty minutes after pneumatic, controlled cortical impact (CCI) injury, C57BI6 mice were randomly assigned to "low dose" (3 mg/kg, LD) or "high dose" (30 mg/kg, HD) s.c. phenothiazine or vehicle treatment. Brain lesion, neurofunctional impairment, body weight, and markers of cerebral inflammation were determined 24h after the insult. Phenothiazine treatment dose-dependently reduced brain lesion volume (LD: -19.8%; HD: -26.1%) and posttraumatic body weight loss. There were no significant differences in the neurological function score and in markers of cerebral inflammation (Iba-1 positive cells, TNFα expression), whereas iNOS expression was significantly lower compared to vehicle-treated animals. Phenothiazine appears to modify in a post-treatment protocol certain aspects of secondary brain damage in vivo at unusually low concentrations, in particular the cortical contusion volume after TBI. The potential role of the reduced iNOS expression is unclear at present.
自由基形成导致的氧化应激是创伤性脑损伤（TBI）后继发性脑损伤的重要机制。已发现吩噻嗪在体外真核细胞和体内无脊椎动物中是一种强大的抗氧化剂。本研究旨在确定未取代的吩噻嗪在急性脑损伤模型中的神经保护效力。在进行气动控制皮质撞击（CCI）损伤30分钟后，将C57BI6小鼠随机分为“低剂量”（3mg/kg，LD）或“高剂量”（30mg/kg，HD）皮下注射吩噻嗪组或溶剂对照组。在损伤后24小时测定脑损伤、神经功能损害、体重和脑炎症标志物。吩噻嗪治疗剂量依赖性地减少脑损伤体积（LD：-19.8%；HD：-26.1%）和创伤后体重减轻。神经功能评分和脑炎症标志物（Iba-1阳性细胞、TNFα表达）无显著差异，而与溶剂处理组动物相比，诱导型一氧化氮合酶（iNOS）表达显著降低。吩噻嗪似乎在治疗后方案中以异常低的浓度改变了体内继发性脑损伤的某些方面，特别是TBI后的皮质挫伤体积。目前尚不清楚iNOS表达降低的潜在作用。
