Severe Brief Pressure-Controlled Hemorrhagic Shock after Traumatic Brain Injury Exacerbates Functional Deficits and Long-Term Neuropathological Damage in Mice
Severe Brief Pressure-Controlled Hemorrhagic Shock after Traumatic Brain Injury Exacerbates Functional Deficits and Long-Term Neuropathological Damage in Mice
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DOI：
10.1089/neu.2011.2303
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发表时间：
2012-08-01
影响因子：
4.2
通讯作者：
Kochanek, Patrick M.
中科院分区：
文献类型：
--
作者：
Hemerka, Joseph N.;Wu, Xianren;Kochanek, Patrick M.
创伤性脑损伤（TBI）后低血压影响预后。我们发表了第一份使用容量控制方法在小鼠中进行TBI加出血性休克（HS）的报告，并注意到神经元死亡增加。为了在HS期间严格控制血压，需要压力控制HS模型。我们的假设是，与单独的TBI或HS相比，小鼠TBI后短暂、严重的压力控制HS将加剧功能缺陷和神经病理学。将C57BL 6雄性小鼠随机分为四组（n = 10/组）：假手术组、HS组、对照皮质撞击（CCI）组和CCI + HS组。我们使用压力控制休克期（平均动脉压[MAP]= 25 - 27 mm Hg，持续35 min）和轻度至中度CCI后的治疗，包括90 min院前阶段，在此期间给予乳酸林格氏溶液以维持MAP> 70 mm Hg，以及住院阶段，当流出的血液重新输注时。在第14 - 20天，在Morris水迷宫（MWM，隐藏平台范例）中评价小鼠。在第21天，定量病变和半球体积。在24小时、7天或21天（n = 5/组/时间点）在小鼠（n = 60）中评价神经病理学和海马神经元计数（苏木精和伊红[H & E]、Fluoro-Jade B和NeuN）。HS和CCI + HS组在休克期的MAP降低（p <0.05）。入院前阶段的液体需求在CCI + HS组中最大（p <0.05），并且HS与假手术和CCI动物相比增加（p <0.05）。CCI + HS后第14、15天MWM潜伏期延长（p <0.05）。CCI + HS组的游泳速度和可见平台潜伏期受损（p <0.05）。CCI + HS动物相对于CCI组具有增加的挫伤体积（p <0.05）。CCI + HS组与CCI组相比，半球体积损失增加了33.3%（p <0.05）。在CCI + HS和CCI动物中在24小时和7天时观察到CA 1细胞损失（p <0.05）。在CCI + HS后观察到CA3细胞损失（在24小时和7天时p <0.05）。仅在CCI + HS动物中观察到21天时的CA 1细胞损失（p <0.05）。与CCI或单纯HS相比，CCI后短暂、严重、压力控制的HS会产生强大的功能缺陷，并加重神经病理学。
Hypotension after traumatic brain injury (TBI) worsens outcome. We published the first report of TBI plus hemorrhagic shock (HS) in mice using a volume-controlled approach and noted increased neuronal death. To rigorously control blood pressure during HS, a pressure-controlled HS model is required. Our hypothesis was that a brief, severe period of pressure-controlled HS after TBI in mice will exacerbate functional deficits and neuropathology versus TBI or HS alone. C57BL6 male mice were randomized into four groups (n = 10/group): sham, HS, controlled cortical impact (CCI), and CCI + HS. We used a pressure-controlled shock phase (mean arterial pressure [MAP] = 25-27 ram Hg for 35 min) and its treatment after mild to moderate CCI including, a 90 min pre-hospital phase, during which lactated Ringer's solution was given to maintain MAP > 70 mm Hg, and a hospital phase, when the shed blood was re-infused. On days 14-20, the mice were evaluated in the Morris water maze (MWM, hidden platform paradigm). On day 21, the lesion and hemispheric volumes were quantified. Neuropathology and hippocampal neuron counts (hematoxylin and eosin [H&E], Fluoro-Jade B, and NeuN) were evaluated in the mice (n=60) at 24 h, 7 days, or 21 days (n = 5/group/time point). HS reduced MAP during the shock phase in the HS and CCI+HS groups (p < 0.05). Fluid requirements during the pre-hospital phase were greatest in the CCI + HS group (p < 0.05), and were increased in HS versus sham and CCI animals (p < 0.05). MWM latency was increased on days 14 and 15 after CCI + HS (p < 0.05). Swim speed and visible platform latency were impaired in the CCI + HS group (p < 0.05). CCI+HS animals had increased contusion volume versus the CCI group ( p < 0.05). Hemispheric volume loss was increased 33.3% in the CCI + HS versus CCI group (p < 0.05). CA1 cell loss was seen in CCI + HS and CCI animals at 24 h and 7 days (p < 0.05). CA3 cell loss was seen after CCI+HS (p < 0.05 at 24h and 7 days). CA1 cell loss at 21 days was seen only in CCI+HS animals (p < 0.05). Brief, severe, pressure-controlled HS after CCI produces robust functional deficits and exacerbates neuropathology versus CCI or HS alone.