Background

Hypoxic ischemic (HI) insults during pregnancy and birth can result in neurodevelopmental disorders, such as cerebral palsy. We have previously shown that a single dose of umbilical cord blood (UCB) cells is effective at reducing short-term neuroinflammation and improves short and long-term behavioural outcomes in rat pups. A single dose of UCB was not able to modulate long-term neuroinflammation or brain tissue loss. In this study we examined whether multiple doses of UCB can modulate neuroinflammation, decrease cerebral tissue damage and improve behavioural outcomes when followed up long-term.

Methods

HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received either 1 dose (PND11), or 3 doses (PND11, 13, 20) of UCB cells. Rats were followed with behavioural testing, to assess both motor and cognitive outcomes. On PND50, brains were collected for analysis.

Results

HI brain injury in rat pups caused significant behavioural deficits. These deficits were significantly improved by multiple doses of UCB. HI injury resulted in a significant decrease in brain weight and left hemisphere tissue, which was improved by multiple doses of UCB. HI resulted in increased cerebral apoptosis, loss of neurons and upregulation of activated microglia. Multiple doses of UCB modulated these neuropathologies. A single dose of UCB at PND11 did not improve behavioural or neuropathological outcomes.

Conclusions

Treatment with repeated doses of UCB is more effective than a single dose for reducing tissue damage, improving brain pathology and restoring behavioural deficits following perinatal brain injury.

中文翻译：

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多剂量脐带血细胞可改善新生大鼠的长期脑损伤。

背景

怀孕和分娩期间的缺氧缺血 (HI) 损伤会导致神经发育障碍，例如脑瘫。我们之前已经表明，单剂量的脐带血 (UCB) 细胞可有效减少短期神经炎症，并改善幼鼠的短期和长期行为结果。单剂量的 UCB 无法调节长期神经炎症或脑组织损失。在这项研究中，我们检查了多剂量 UCB 是否可以调节神经炎症、减少脑组织损伤并改善长期随访时的行为结果。

方法

使用颈动脉结扎的 Rice-Vannucci 方法在出生后第 10 天 (PND10) 大鼠幼崽中诱导 HI 损伤。幼崽接受 1 剂 (PND11) 或 3 剂 (PND11、13、20) 的 UCB 细胞。对大鼠进行行为测试，以评估运动和认知结果。在 PND50 上，收集大脑进行分析。

结果

大鼠幼崽的 HI 脑损伤导致显着的行为缺陷。多剂量的 UCB 显着改善了这些缺陷。HI 损伤导致脑重量和左半球组织显着减少，多剂量 UCB 可改善这种情况。HI 导致脑细胞凋亡增加、神经元丢失和活化小胶质细胞上调。多剂量的 UCB 调节了这些神经病理学。PND11 的单剂量 UCB 没有改善行为或神经病理学结果。

结论

在减少组织损伤、改善脑病理和恢复围产期脑损伤后的行为缺陷方面，重复剂量的 UCB 治疗比单次剂量更有效。