Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (7): 3055-3062.doi: 10.4103/NRR.NRR-D-24-01150

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Telomere length as a predictive marker for long-term cognitive function in a mouse model of subarachnoid hemorrhage 

Qia Zhang1, 2, #, Chaoran Xu1, 3, #, Jiayong Fan1, Chengjian Lou1, Jiarui Chen2, Jianmin Zhang1, 2, *, Jun Mo1, *   

  1. 1Department 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; 
    2Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China;
    3Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • Online:2026-07-15 Published:2026-03-31
  • Contact: Zhang, MD, zjm135@zju.edu.cn; Jun Mo, MD, mojun@zju.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81901336 (to JM).

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Abstract:

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.

Key words: acetyl-coenzyme A synthetase-2, brain aging, DNA damage response, long-term prognosis, subarachnoid hemorrhage, telomere length