From the Division of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery (P.B., A.T., M.C., M.C.C., P.S., P.M.-Q., C.J., L.J.K., J.L.P.), and Center for Brain Injury and Repair, Department of Neurosurgery (P.B., A.T., M.C., M.C.C., P.S., A.P.G., E.A., K.D.B., C.J., L.J.K., D.F.M., D.H.S., J.L.P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
J Trauma Acute Care Surg. 2024 Nov 1;97(5):776-784. doi: 10.1097/TA.0000000000004400. Epub 2024 May 20.
Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI.
CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on Day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction ( p < 0.05).
On Day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 ( p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 ( p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones ( p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones ( p < 0.05).
Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.
创伤性脑损伤 (TBI) 引发的认知缺陷是由神经炎症和脑水肿引起的。最近发现，常用的非典型抗精神病药喹硫平 (QTP) 可改善 TBI 后的预后。我们假设 QTP 会因此改善严重 TBI 后 2 周的动物学习和记忆能力。
CD1 雄性小鼠 (n = 35) 接受严重 TBI（皮质控制冲击，损伤，I）或假手术（S），随后接受 BID 生理盐水（P，安慰剂）或 QTP（10 或 20 mg/kg，IP）治疗 2 周。动物接受 Morris 水迷宫 (MWM) 运动以评估空间学习和记忆。从使用 Ethovision 软件分析的数字视频记录中计算游泳动物到达位于象限 1 (Z1) 的平台区域 (Z5) 的距离和时间。每天记录动物体重，并在第 14 天获取受伤大脑半球以确定水肿程度（湿重-干重比）。使用 ANOVA/Bonferroni 校正评估组间差异（p < 0.05）。
在第 14 天，与 I + QTP20 和 I + QTP10 相比，I + P 组的动物体重减轻恢复最低（p ≤ 0.01）。I + P 组的脑水肿最大，仅在 I + QTP20 组中显著降低（p < 0.05）。两种 QTP 剂量均通过显著减少到达目标区域的潜伏期和行进距离来改善空间学习（p < 0.05）。在探测记忆试验中，只有 I + QTP20 而不是 I + QTP10 显著有利于动物进入或穿过目标区域（p < 0.05）。
TBI 后 QTP 可减轻脑水肿，并改善空间学习和记忆，具有潜在的剂量依赖性影响，可在 14 天内改善记忆。这些数据表明，在脑损伤后 QTP 具有意外获益，应特别加以探索。
