Zhang Qia, Xu Chaoran, Fan Jiayong, Lou Chengjian, Chen Jiarui, Zhang Jianmin, Mo Jun
Department of Neurosurgery, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang Province, China.
Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Neural Regen Res. 2025 Jun 19. doi: 10.4103/NRR.NRR-D-24-01150.
Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis. Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage. However, there is notable absence of biological markers to predict long-term prognosis in this patient population. Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage, this study postulates that telomere length, a recognized biomarker for aging, could be used as a prognostic indicator for subarachnoid hemorrhage. A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage. Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals. Concurrently, the relative telomere length was analyzed by quantitative polymerase chain reaction, which was performed using DNA extracted from ear notch and brain tissue after each assessment. Furthermore, proteomic analysis was employed to investigate differential protein expression in hippocampal tissue. Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time. There was a significant positive correlation between telomere length and neurological test scores, confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage. Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes, energy metabolism, and cellular signal transduction. This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice. Thus, telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.
蛛网膜下腔出血是中风的一种亚型，可导致严重的神经损伤，并与长期预后不良相关。认知障碍是蛛网膜下腔出血患者长期神经功能障碍的主要表现。然而，在这一患者群体中，显著缺乏预测长期预后的生物标志物。鉴于蛛网膜下腔出血相关的类似衰老的神经认知现象，本研究推测端粒长度，一种公认的衰老生物标志物，可作为蛛网膜下腔出血的预后指标。使用左颈内动脉血管内穿刺小鼠模型模拟蛛网膜下腔出血。通过每隔一个月进行的神经行为评估获得综合神经测试分数。同时，通过定量聚合酶链反应分析相对端粒长度，该反应在每次评估后使用从耳缘和脑组织中提取的DNA进行。此外，采用蛋白质组学分析来研究海马组织中的差异蛋白质表达。蛛网膜下腔出血小鼠在较长时间内表现出持续的神经认知障碍。端粒长度与神经测试分数之间存在显著正相关，证实了端粒长度作为蛛网膜下腔出血预后指标的有用性。蛛网膜下腔出血小鼠的海马组织显示乙酰辅酶A合成酶-2表达降低，以及与核糖体、能量代谢和细胞信号转导相关的蛋白质表达异常。本研究证实了蛛网膜下腔出血小鼠大脑中端粒缩短和海马体中的代谢紊乱。因此，端粒长度是实验性蛛网膜下腔出血后小鼠认知功能长期损害的预测标志物。
