2. Academic Validation
  3. Urolithin A alleviates early brain injury after subarachnoid hemorrhage by regulating the AMPK/mTOR pathway-mediated autophagy

Urolithin A alleviates early brain injury after subarachnoid hemorrhage by regulating the AMPK/mTOR pathway-mediated autophagy

  • Neurochirurgie. 2023 Aug 18;69(5):101480. doi: 10.1016/j.neuchi.2023.101480.
Meiqiu Liu 1,  Zhen Chen 2,  Huan Zhang 3,  Zhiji Cai 1,  Tiancheng Liu 2,  Mengli Zhang 2,  Xian Wu 2,  Fen Ai 2,  Ganzhe Liu 4,  Chao Zeng 5,  Jiancheng Shen 6
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Ningde Municipal Hospital of Ningde Normal University, Ningde 352000, China.
  • 2 Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
  • 3 Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
  • 4 Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
  • 5 Department of Neurosurgery, Ningde Municipal Hospital of Ningde Normal University, Ningde 352000, China. Electronic address: zc414822@126.com.
  • 6 Department of Neurosurgery, Ningde Municipal Hospital of Ningde Normal University, Ningde 352000, China. Electronic address: 190996473@qq.com.
PMID: 37598622 DOI: 10.1016/j.neuchi.2023.101480
Abstract

Objective: Unfavorable outcomes in patients with subarachnoid hemorrhage (SAH) are mainly attributed to early brain injury (EBI). Reduction of neuronal death can improve the prognosis in SAH patients. Autophagy and Apoptosis are critical players in neuronal death. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins and ellagic acid. Here, we detected the role of UA in EBI post-SAH.

Methods: We established an animal model of SAH in rats by endovascular perforation, with administration of UA, 3-methyladenine (3-MA) and Compound C. SAH grading, neurological function, brain water content, western blotting analysis of levels of proteins related to Apoptosis, Autophagy and pathways, blood-brain barrier (BBB) integrity, TUNEL staining, and immunofluorescence staining of LC3 were evaluated at 24h after SAH.

Results: SAH induction led to neurological dysfunctions, BBB disruption, and cerebral edema at 24h post-SAH in rats, which were relieved by UA. Additionally, cortical neuronal Apoptosis in SAH rats was also attenuated by UA. Moreover, UA restored Autophagy level in SAH rats. Mechanistically, UA activated the AMPK/mTOR pathway. Furthermore, inhibition of Autophagy and AMPK limited UA-mediated protection against EBI post-SAH CONCLUSION: UA alleviates neurological deficits, BBB permeability, and cerebral edema by inhibiting cortical neuronal Apoptosis through regulating the AMPK/mTOR pathway-dependent Autophagy in rats following SAH.

Keywords

AMPK/mTOR; Autophagy; Early brain injury; Subarachnoid hemorrhage; Urolithin A.

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