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Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review)

  • Authors:
    • Rijin Lin
    • Sheng Guan
    • Jian Wang
    • Mingyang Han
    • Mengyan Fan
    • Jiaxin Wan
    • Xiaowen Zhang
    • Nan Zhang
    • Jing Li
  • View Affiliations / Copyright

    Affiliations: Department of Neurointervention, The First Affiliated Hospital of Zhengzhou University, Henan Provincial Neurointerventional Engineering Research Center, Zhengzhou, Henan 450003, P.R. China, Department of Human Anatomy, School of Basic Medical Sciences, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 256
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    Published online on: July 14, 2025
       https://doi.org/10.3892/mmr.2025.13621
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Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a subtype of stroke associated with high morbidity and mortality rates worldwide, posing challenges in developing effective treatment strategies. The present review aimed to summarize the role of inflammation and pyroptosis in early brain injury (EBI), a key determinant of outcomes in aSAH, the interplay between oxidative stress, neuroinflammation and cell death and the immune‑inflammatory response and oxidative stress as central components in the pathogenesis of aSAH. Key signaling pathways include toll‑like receptor 4/NF‑κB and NLR family pyrin domain‑containing 3/gasdermin D pathways, which regulate inflammatory responses and pyroptotic cell death. Additionally, current and traditional Chinese therapeutic approaches to mitigating EBI and improving patient outcomes are summarized, demonstrating the potential roles of salvianolic acid B, pterostilbene, luteolin and electro‑acupuncture. The findings of the present review underscore the necessity for continued research into the molecular mechanisms underlying aSAH to translate these insights into clinical practice, enhancing patient survival and recovery.
View Figures

Figure 1

Inflammation signaling pathways in
early brain injury. After intracranial aneurysm ruptures, blood
enters the subarachnoid space and red blood cells release oxygen,
hemoglobin and other breakdown products as DAMPs. TLR4 recognizes
DAMPs and triggers immune cascade reactions. Inflammatory cytokines
upregulate MMP-9, ZO-1 and other structure proteins, which damages
the tight junction of BBB; disrupted BBB will further lead to
increased neuroinflammation. Meanwhile, hemoglobin through the
hemoglobin metabolite axis of hemoglobin-heme-iron further
decomposes into heme, and heme further decomposes bilirubin and
free iron. The free iron catalyzes the production of ROS, and ROS
induces NLRP3 inflammasome, which leads to the activation of
caspase-1. This active caspase-1 then triggers the activation of
GSDMD and the cellular inflammatory response, the activated GSDMD
induces apoptosis and pyroptosis. DAMP, damage associated molecular
pattern; zonula occludens-1, ZO-1; BBB, blood brain barrier; ROS,
reactive oxygen species; NLRP3, NLR family pyrin domain containing
3; GSDMD, gasdermin D; ASC, apoptosis-associated speck-like protein
containing a caspase recruitment domain.
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Copy and paste a formatted citation
Spandidos Publications style
Lin R, Guan S, Wang J, Han M, Fan M, Wan J, Zhang X, Zhang N and Li J: Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review). Mol Med Rep 32: 256, 2025.
APA
Lin, R., Guan, S., Wang, J., Han, M., Fan, M., Wan, J. ... Li, J. (2025). Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review). Molecular Medicine Reports, 32, 256. https://doi.org/10.3892/mmr.2025.13621
MLA
Lin, R., Guan, S., Wang, J., Han, M., Fan, M., Wan, J., Zhang, X., Zhang, N., Li, J."Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review)". Molecular Medicine Reports 32.3 (2025): 256.
Chicago
Lin, R., Guan, S., Wang, J., Han, M., Fan, M., Wan, J., Zhang, X., Zhang, N., Li, J."Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review)". Molecular Medicine Reports 32, no. 3 (2025): 256. https://doi.org/10.3892/mmr.2025.13621
Copy and paste a formatted citation
x
Spandidos Publications style
Lin R, Guan S, Wang J, Han M, Fan M, Wan J, Zhang X, Zhang N and Li J: Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review). Mol Med Rep 32: 256, 2025.
APA
Lin, R., Guan, S., Wang, J., Han, M., Fan, M., Wan, J. ... Li, J. (2025). Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review). Molecular Medicine Reports, 32, 256. https://doi.org/10.3892/mmr.2025.13621
MLA
Lin, R., Guan, S., Wang, J., Han, M., Fan, M., Wan, J., Zhang, X., Zhang, N., Li, J."Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review)". Molecular Medicine Reports 32.3 (2025): 256.
Chicago
Lin, R., Guan, S., Wang, J., Han, M., Fan, M., Wan, J., Zhang, X., Zhang, N., Li, J."Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review)". Molecular Medicine Reports 32, no. 3 (2025): 256. https://doi.org/10.3892/mmr.2025.13621
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