Gornicka-Pawlak Elzbieta, Janowski Miroslaw, Habich Aleksandra, Jablonska Anna, Sypecka Joanna, Lukomska Barbara
NeuroRepair Department, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Front Neurol. 2019 Aug 13;10:786. doi: 10.3389/fneur.2019.00786. eCollection 2019.
Focal brain injury is a leading cause of serious disability significantly worsening patients' quality of life. Such damage disrupts the existing circuits, leads to motor, and cognitive impairments as well as results in a functional asymmetry. To date, there is still no therapy to effectively restore the lost functions. We examined the effectiveness of human umbilical cord blood (HUCB)-derived cells after their intra-arterial infusion following focal stroke-like brain damage. The model of stroke was performed using ouabain stereotactic injection into the right dorsolateral striatum in rats. Two days following the brain injury 10 cells were infused into the right carotid artery. The experimental animals were placed into enriched environment housing conditions to enhance the recovery process. Behavioral testing was performed using a battery of tasks visualizing motor as well as cognitive deficits for 30 days following brain injury. We assessed animal asymmetry while they were moving forward at time of testing in different tasks. We found that intra-arterial infusion of HUCB-derived cells inversed lateralized performance resulting from the focal brain injury at the early stage of T-maze habit learning task training. The inversion was independent from the level of neural commitment of infused cells. The learning asymmetry inversion was observed only under specific circumstances created by the applied task design. We did not found such inversion in walking beam task, vibrissae elicited forelimb placing, the first exploration of open field, T-maze switching task as well as apomorphine induced rotations. Both the asymmetry induced by the focal brain injury and its inversion resulting from cell infusion decreased along the training. The inversion of learning asymmetry was also independent on the range of the brain damage. Intra-arterial infusion of HUCB-derived cells inversed lateralized performance of learning task resulting from focal brain damage. The inversion was not visible in any other of the used motor as well as cognitive tests. The observed behavioral effect of cell infusion was also not related to the range of the brain damage. Our findings contribute to describing the effects of systemic treatment with the HUCB-derived cells on functional recovery following focal brain injury.
局灶性脑损伤是导致严重残疾的主要原因，会显著恶化患者的生活质量。这种损伤会破坏现有的神经回路，导致运动和认知障碍，并造成功能不对称。迄今为止，仍没有有效的疗法来恢复丧失的功能。我们研究了局灶性中风样脑损伤后经动脉输注人脐带血（HUCB）来源的细胞的有效性。通过向大鼠右侧背外侧纹状体立体定向注射哇巴因来建立中风模型。脑损伤两天后，将10个细胞注入右侧颈动脉。将实验动物置于丰富环境饲养条件下以促进恢复过程。在脑损伤后的30天内，使用一系列任务进行行为测试，以观察运动和认知缺陷。在测试不同任务时，我们评估了动物向前移动时的不对称性。我们发现，在T迷宫习惯学习任务训练的早期阶段，经动脉输注HUCB来源的细胞可逆转局灶性脑损伤导致的侧向化表现。这种逆转与输注细胞的神经分化水平无关。仅在应用任务设计所创造的特定情况下观察到学习不对称性的逆转。在走平衡木任务、触须诱发前肢放置、旷场首次探索、T迷宫转换任务以及阿扑吗啡诱导的旋转中，我们未发现这种逆转。局灶性脑损伤诱导的不对称性及其因细胞输注导致的逆转均随着训练而降低。学习不对称性的逆转也与脑损伤范围无关。经动脉输注HUCB来源的细胞可逆转局灶性脑损伤导致的学习任务的侧向化表现。在任何其他所使用的运动和认知测试中均未见到这种逆转。观察到的细胞输注行为效应也与脑损伤范围无关。我们的研究结果有助于描述用HUCB来源的细胞进行全身治疗对局灶性脑损伤后功能恢复的影响。
