National Trauma Research Institute, The Alfred Hospital, 89 Commercial Road, Melbourne 3004, Australia.
J Neuroinflammation. 2011 Oct 28;8:147. doi: 10.1186/1742-2094-8-147.
The combination of diffuse brain injury with a hypoxic insult is associated with poor outcomes in patients with traumatic brain injury. In this study, we investigated the impact of post-traumatic hypoxia in amplifying secondary brain damage using a rat model of diffuse traumatic axonal injury (TAI). Rats were examined for behavioral and sensorimotor deficits, increased brain production of inflammatory cytokines, formation of cerebral edema, changes in brain metabolism and enlargement of the lateral ventricles.
Adult male Sprague-Dawley rats were subjected to diffuse TAI using the Marmarou impact-acceleration model. Subsequently, rats underwent a 30-minute period of hypoxic (12% O2/88% N2) or normoxic (22% O2/78% N2) ventilation. Hypoxia-only and sham surgery groups (without TAI) received 30 minutes of hypoxic or normoxic ventilation, respectively. The parameters examined included: 1) behavioural and sensorimotor deficit using the Rotarod, beam walk and adhesive tape removal tests, and voluntary open field exploration behavior; 2) formation of cerebral edema by the wet-dry tissue weight ratio method; 3) enlargement of the lateral ventricles; 4) production of inflammatory cytokines; and 5) real-time brain metabolite changes as assessed by microdialysis technique.
TAI rats showed significant deficits in sensorimotor function, and developed substantial edema and ventricular enlargement when compared to shams. The additional hypoxic insult significantly exacerbated behavioural deficits and the cortical production of the pro-inflammatory cytokines IL-6, IL-1β and TNF but did not further enhance edema. TAI and particularly TAI+Hx rats experienced a substantial metabolic depression with respect to glucose, lactate, and glutamate levels.
Altogether, aggravated behavioural deficits observed in rats with diffuse TAI combined with hypoxia may be induced by enhanced neuroinflammation, and a prolonged period of metabolic dysfunction.
弥漫性脑损伤合并缺氧损伤与创伤性脑损伤患者的不良预后相关。在这项研究中，我们使用弥漫性创伤性轴索损伤（TAI）大鼠模型研究了创伤后缺氧对继发性脑损伤的放大作用。通过行为和感觉运动缺陷、大脑促炎细胞因子产生增加、脑水肿形成、脑代谢变化和侧脑室扩大来评估大鼠。
成年雄性 Sprague-Dawley 大鼠使用 Marmarou 撞击-加速模型进行弥漫性 TAI。随后，大鼠接受 30 分钟的低氧（12% O2/88% N2）或常氧（22% O2/78% N2）通气。仅缺氧组和假手术组（无 TAI）分别接受 30 分钟的低氧或常氧通气。检查的参数包括：1）使用转棒、梁走和胶带去除测试评估行为和感觉运动缺陷，以及自愿开放场探索行为；2）干湿组织重量比法评估脑水肿形成；3）侧脑室扩大；4）促炎细胞因子的产生；5）通过微透析技术评估实时脑代谢物变化。
与假手术组相比，TAI 大鼠表现出明显的感觉运动功能缺陷，并出现明显的脑水肿和脑室扩大。缺氧的额外损伤显著加重了行为缺陷以及皮质中促炎细胞因子 IL-6、IL-1β 和 TNF 的产生，但并未进一步加重水肿。TAI 特别是 TAI+Hx 大鼠的葡萄糖、乳酸和谷氨酸水平出现明显代谢抑制。
弥漫性 TAI 合并缺氧的大鼠观察到的行为缺陷加重可能是由神经炎症增强和代谢功能障碍延长引起的。
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