Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.
Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.
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DOI：
10.1016/j.nbd.2020.105084
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发表时间：
2020-11
影响因子：
6.1
通讯作者：
Waldau B
中科院分区：
文献类型：
--
作者：
Kamal K;Keiter JA;Binyamin TR;de la Cruz Dapula JN;Vergara AR;Hawk CW;Izadi A;Lyeth B;Gurkoff GG;Sharp FR;Waldau B
室壁性脑室内出血(IVH)的幸存者可能会康复，并伴有明显的学习和记忆障碍。本研究的目的是探讨脑室壁瘤破裂后记忆减退的机制。我们通过向右侧脑室注入自体动脉血两分钟，建立了一种动脉瘤样室内出血大鼠模型。我们还评估了容量匹配的人工脑脊液(CSF)控制、凝血酶和输送方式(脉冲手注射与持续泵输注)的效果。我们在1周和5周后进行磁共振脑成像，以评估脑积水，并在6周后对齿状回进行组织学分析。只有接受了全血脉冲手部注射的动物在5周后出现了空间记忆获得和保持缺陷。这些动物在1周和5周时的脑室比持续泵入全血的动物大。IVH后6周，我们未发现齿状回颗粒细胞神经元减少或齿状回神经发生或分化受损。快速注射血液或体积导致齿状回小胶质细胞激活。综上所述，我们的结果指出机械损伤是脑室壁瘤破裂后记忆力下降的主要机制。然而，体积匹配的人工脑脊液脉冲注射在5周时并没有造成空间记忆障碍。因此，全血本身必须在这一机制中发挥作用。需要进一步的研究来评估血液的粘度是否通过初级损伤机制导致额外的机械破坏和脑积水，或者血液的毒性是否导致继发性损伤机制，从而导致5周后观察到的空间记忆障碍。
Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.
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