Tress Erika E, Clark Robert S B, Foley Lesley M, Alexander Henry, Hickey Robert W, Drabek Tomas, Kochanek Patrick M, Manole Mioara D
University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
University of Pittsburgh, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; University of Pittsburgh, Critical Care Medicine, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA; University of Pittsburgh, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA.
Neurosci Lett. 2014 Aug 22;578:17-21. doi: 10.1016/j.neulet.2014.06.020. Epub 2014 Jun 14.
Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological outcome in most survivors. Development of neuroprotective therapies is contingent upon understanding the permeability of intravenously delivered medications through the blood brain barrier (BBB). In a model of pediatric CA we sought to characterize BBB permeability to small and large molecular weight substances. Additionally, we measured the percent brain water after CA. Asphyxia of 9 min was induced in 16-18 day-old rats. The rats were resuscitated and the BBB permeability to small (sodium fluorescein and gadoteridol) and large (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24 h after asphyxial CA or sham surgery. Percent brain water was measured post-CA and in shams using wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1, 4h and over the entire 24 h post-CA did not differ from shams, suggesting absence of BBB permeability to these solutes. Cerebral water content was increased at 3h post-CA vs. sham. In conclusion, after 9 min of asphyxial CA there is no BBB permeability over 24h to conventional small or large molecule tracers despite the fact that cerebral water content is increased early post-CA indicating the development of brain edema. Evaluation of novel therapies targeting neuronal death after pediatric CA should include their capacity to cross the BBB.
小儿窒息性心脏骤停（CA）导致大多数幸存者出现不良神经学转归。神经保护疗法的发展取决于对静脉给药通过血脑屏障（BBB）的通透性的了解。在小儿CA模型中，我们试图描述BBB对小分子和大分子物质的通透性。此外，我们测量了CA后的脑含水量百分比。对16 - 18日龄大鼠诱导9分钟的窒息。使大鼠复苏，并在窒息性CA或假手术后1、4和24小时评估BBB对小分子（荧光素钠和钆特醇）和大分子（免疫球蛋白G，IgG）的通透性。使用脑湿重与干重测量CA后和假手术组的脑含水量百分比。CA后1、4小时以及整个24小时的荧光、钆特醇摄取或IgG染色与假手术组无差异，表明BBB对这些溶质无通透性。与假手术组相比，CA后3小时脑含水量增加。总之，在9分钟的窒息性CA后，尽管CA后早期脑含水量增加表明脑水肿的发展，但在24小时内BBB对传统小分子或大分子示踪剂无通透性。评估针对小儿CA后神经元死亡的新疗法应包括其穿过BBB的能力。
