Propranolol improves cognitive function and glymphatic system recovery through STAT3/MMP2 pathway after TBI
Dongming Gao , Guohui Huang ,Lei Li, Peng Yu
Abstract
There is no effective treatment for cognitive impairment after traumatic brain injury (TBI). Previous studies have demonstrated that propranolol may improve cognitive function. The glymphatic system plays a crucial role in cognitive impairment after TBI. Thus, we explored the mechanism by which propranolol improves cognitive function and promotes glymphatic system recovery after TBI
Introduction
Traumatic brain injury (TBI) induces multiple symptoms, such as fatigue, headaches, anxiety and cognitive impairment .However, there is still no effective treatment for TBI-induced cognitive impairment. Therefore, it is urgent to explore novel therapeutic strategies for this condition.
Materials and methods
Animals and TBI model
All experiments were performed in accordance with the guidelines approved by the Animal Care and Use Committee of Tongji University. Male Sprague-Dawley rats (12 weeks old, body weight 280–320 g) were randomly assigned to five groups: TBI group, TBI + propranolol group, sham group.
Cell culture
Primary astrocytes were isolated from the cerebral cortex of neonatal rats within 24h after birth. Cerebral cortices were dissected and transferred into sterile tubes. After incubation with 0.25% trypsin (Sigma, St. Louis, MO, USA) for 10 min at 37 °C, the tissue was centrifuged at 1000 rpm for 5 min.
Result
Propranolol improved cognitive function after TBI
Compared with untreated TBI rats, propranolol, S31-201 and SB-3CT all significantly relieved short- and long-term memory deficits in the novel object recognition and odor tests, though none of the three agents fully recovered memory function compared with the normal rats. In the Morris water maze test, propranolol.
Propranolol recovered glymphatic dysfunction in TBI rats
Since propranolol was found to reduce cerebral p-tau and Aβ deposition following TBI, we further examined glymphatic system function. The results revealed that propranolol, S31-201, and SB-3CT totally rescued TBI-induced delay in metabolic waste clearance.
Conclusion
Propranolol may improve cognitive function and glymphatic system recovery after TBI through STAT3/MMP2 pathway.
Citation: Gao D, Huang G, Li L, Yu P (2026) Propranolol improves cognitive function and glymphatic system recovery through STAT3/MMP2 pathway after TBI. PLoS One 21(8): e0353852. https://doi.org/10.1371/journal.pone.0353852
Editor: Firas H. Kobeissy, University of Florida, UNITED STATES OF AMERICA
Received: September 2, 2025; Accepted: June 30, 2026; Published: August 21, 2026
Copyright: © 2026 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: The work is supported by the National Natural Science Foundation of China (grant Nos. 81801217 and 81801215, external fund). There was no additional external funding received for this study.
Competing interests: The authors have declared that no competing interests exist.
