Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
J Neurotrauma. 2010 Aug;27(8):1449-61. doi: 10.1089/neu.2010.1331.
Arginine vasopressin (AVP) has previously been shown to promote disruption of the blood-brain barrier, exacerbate edema, and augment the loss of neural tissue in various forms and models of brain injury. However, the mechanisms underlying these AVP actions are not well understood. These mechanisms were studied in AVP-deficient Brattleboro rats (Avp(di/di)), and their parental Long-Evans strain, using a controlled cortical impact model of traumatic brain injury (TBI). The increased influx of inflammatory cells into the injured cortex in wild-type versus Avp(di/di) rats was associated with higher levels of cortical synthesis of the CXC and CC chemokines found in wild-type versus Avp(di/di) rats. These chemokines were predominantly produced by the cerebrovascular endothelium and astrocytes. In astrocyte and brain endothelial cell cultures, AVP acted synergistically with tumor necrosis factor-alpha (TNF-alpha) to increase the TNF-alpha-dependent production of CXC and CC chemokines. These AVP actions were mediated by c-Jun N-terminal kinase (JNK), as shown by Western blotting and pharmacological inhibition of JNK activity. The activity of JNK was increased in response to injury, and the differences in the magnitude of its post-traumatic activation between Avp(di/di) and wild-type rats were observed. These data demonstrate that AVP plays an important role in exacerbating the brain inflammatory response to injury.
精氨酸加压素 (AVP) 先前已被证明可促进血脑屏障的破坏，加重水肿，并加剧各种形式和模型的脑损伤中神经组织的丧失。然而，这些 AVP 作用的机制尚不清楚。这些机制在 AVP 缺乏的 Brattleboro 大鼠（Avp(di/di)）及其亲本 Long-Evans 品系中，使用创伤性脑损伤（TBI）的皮质控制撞击模型进行了研究。与 Avp(di/di) 大鼠相比，野生型大鼠受伤皮质中炎症细胞的增加与皮质中 CXC 和 CC 趋化因子的合成水平升高有关，而这些趋化因子在野生型大鼠中发现的水平高于 Avp(di/di) 大鼠。这些趋化因子主要由脑血管内皮细胞和星形胶质细胞产生。在星形胶质细胞和脑内皮细胞培养物中，AVP 与肿瘤坏死因子-α（TNF-α）协同作用，增加 TNF-α 依赖性 CXC 和 CC 趋化因子的产生。这些 AVP 作用是通过 c-Jun N 末端激酶（JNK）介导的，如 Western blot 和 JNK 活性的药理学抑制所证明的。JNK 的活性在受伤后增加，并且在 Avp(di/di) 和野生型大鼠之间观察到其创伤后激活幅度的差异。这些数据表明，AVP 在加剧损伤后大脑炎症反应中发挥重要作用。
