深低温停循环激活新生脑内神经前体细胞。

Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain.

机构信息

Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California.

出版信息

Ann Thorac Surg. 2020 Dec;110(6):2076-2081. doi: 10.1016/j.athoracsur.2020.02.058. Epub 2020 Mar 30.

DOI:10.1016/j.athoracsur.2020.02.058

PMID:32240645

Abstract

BACKGROUND

Use of antegrade cerebral perfusion (ACP) as an alternative neuroprotection strategy to deep hypothermic circulatory arrest (DHCA) in the setting of cardiopulmonary bypass in neonates has become a common approach, although the value of ACP over DHCA remains highly debated. This study investigated the disruption to neonatal brain homeostasis by DHCA and ACP.

METHODS

Neonatal pigs (7 days old) undergoing bypass were assigned to 4 groups: DHCA at 18°C and ACP at 18°, 25°, and 32° for 45 minutes (n = 6 per group). ACP was initiated through the innominate artery and maintained at 40 mL/kg/min. After bypass, all animals were maintained sedated and intubated for 24 hours before being euthanized. Brain subventricular zone tissues were analyzed for histologic injury by assessing apoptosis and neural homeostasis (Nestin).

RESULTS

Histologic examination showed no significant ischemic/hypoxic neuronal death at any cooling temperature among the 4 treatment groups. However, we detected a significantly higher apoptotic rate in DHCA compared with ACP at 18°C (P = .003-.017) or 25°C (P = .012-.043), whereas apoptosis at 32°C was not different from DHCA. Of note, we identified increased Nestin expression in the DHCA group compared with all ACP groups (P range = .011-.041).

CONCLUSIONS

Neonatal piglet ACP at 18° or 25°C provides adequate protection from increased brain cellular apoptosis. In contrast to ACP, however, DHCA induces brain Nestin expression, indicating activation of neural progenitor cells and the potential of altering neonatal neurodevelopmental progression. DHCA has potential to more profoundly disrupt neural homeostasis than does ACP.

摘要

背景

在体外循环中，使用顺行性脑灌注（ACP）作为替代深低温循环停止（DHCA）的神经保护策略在新生儿中已成为一种常见方法，尽管 ACP 相对于 DHCA 的价值仍存在高度争议。本研究旨在探讨 DHCA 和 ACP 对新生儿大脑内稳态的破坏。

方法

接受旁路手术的新生仔猪（7 天大）被分为 4 组：DHCA 组在 18°C 下进行，ACP 组分别在 18°C、25°C 和 32°C 下进行 45 分钟（每组 6 只）。ACP 通过无名动脉开始，并维持在 40mL/kg/min。旁路后，所有动物均镇静并插管 24 小时，然后安乐死。通过评估凋亡和神经内稳态（Nestin）来分析脑室下区组织的组织学损伤。

结果

组织学检查显示，在 4 个治疗组中，任何冷却温度下均未观察到明显的缺血/缺氧性神经元死亡。然而，与 18°C 时的 ACP 相比，DHCA 组的凋亡率显著升高（P=0.003-0.017）或 25°C 时（P=0.012-0.043），而 32°C 时的凋亡率与 DHCA 无差异。值得注意的是，与所有 ACP 组相比，DHCA 组的 Nestin 表达增加（P 范围=0.011-0.041）。