aDepartment of Neurology, The Fourth Central Clinical College, Tianjin Medical University, Tianjin, China
bDepartment of Gastroenterology, The Fourth Central Clinical College, Tianjin Medical University, Tianjin, China
cMetabolic Center, The Fourth Central Clinical College, Tianjin Medical University, Tianjin, China
dDepartment of Neurology, Tianjin Medical University General Hospital, Tianjin, China
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Article / Publication DetailsFirst-Page Preview
Received: May 21, 2021
Accepted: January 15, 2022
Published online: March 29, 2023
Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0
ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)
For additional information: https://www.karger.com/NPS
AbstractIntroduction: Inflammation is closely associated with the pathogenesis of vascular dementia (VD). Dl-3-n-butylphthalide (NBP) is a small molecule compound extracted from the seeds of Chinese celery, which have anti-inflammatory properties in animal models of acute ischemia and patients with stroke. In this experiment, we studied the protective effects of NBP in a rat model of VD induced by permanent bilateral occlusion of the common carotid arteries and investigated the role of the TLR-4/NF-κB inflammatory signaling pathway in the pathology of VD. Methods: The Morris water maze test was used to evaluate cognitive deficits in the VD rats. Western blot, immunohistochemistry, and PCR analyses were used to analyze the molecular basis of the inflammatory response. Results: NBP significantly improved the learning and memory ability of VD rats. With regard to the protective mechanism, the results showed that NBP significantly downregulated the relative expression of Cleaved Cas-1/Cas-1 and Cleaved GSDMD/GSDMD. Moreover, NBP decreased the levels of the TLR-4 and NF-κB (P65) protein and phosphorylation of P65 in the hippocampus of VD rats via the TLR-4/NF-κB signaling pathway. Conclusion: These findings demonstrate that NBP protects against memory deficits in permanent bilateral common carotid artery occlusion-induced VD rats by attenuating pyroptosis via the TLR-4/NF-κB signaling pathway.
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References van de Vorst IE, Koek HL, de Vries R, Bots ML, Reitsma JB, Vaartjes I. Effect of vascular risk factors and diseases on mortality in individuals with dementia: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64:37–46. Liu Q, Bhuiyan MIH, Liu R, Song S, Begum G, Young CB, et al. Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function. J Neuroinflammation. 2021;18(1):187. Cong Lin ZZ. Dynamic behavioral assessment of vascular dementia rat models made by bilateral common carotid artery occlusion. Lab Anim Comp Med. 2020;40:22–7. Poh L, Fann DY, Wong P, Lim HM, Foo SL, Kang SW, et al. AIM2 inflammasome mediates hallmark neuropathological alterations and cognitive impairment in a mouse model of vascular dementia. Mol Psychiatry. 2021 Aug;26(8):4544–60. Shen H, Han C, Yang Y, Guo L, Sheng Y, Wang J, et al. Pyroptosis executive protein GSDMD as a biomarker for diagnosis and identification of Alzheimer’s disease. Brain Behav. 2021;11(4):e02063. Yuan R, Zhao W, Wang QQ, He J, Han S, Gao H, et al. Cucurbitacin b inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. Pharmacol Res. 2021;170:105748. Li J, Li Y, Ogle M, Zhou X, Song M, Yu SP, et al. Dl-3-n-butylphthalide prevents neuronal cell death after focal cerebral ischemia in mice via the JNK pathway. Brain Res. 2010;1359:216–26. Huang JZ, Chen YZ, Su M, Zheng HF, Yang YP, Chen J, et al. Dl-3-n-butylphthalide prevents oxidative damage and reduces mitochondrial dysfunction in an mpp(+)-induced cellular model of parkinson’s disease. Neurosci Lett. 2010;475:89–94. Abdoulaye IA, Guo YJ. A review of recent advances in neuroprotective potential of 3-n-butylphthalide and its derivatives. Biomed Res Int. 2016;2016:5012341. Wang F, Ma J, Han F, Guo X, Meng L, Sun Y, et al. Dl-3-n-butylphthalide delays the onset and progression of diabetic cataract by inhibiting oxidative stress in rat diabetic model. Sci Rep. 2016;6:19396. Dong GX, Feng YP. Effects of NBP on ATPase and anti-oxidant enzymes activities and lipid peroxidation in transient focal cerebral ischemic rats. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002;24:93–7. Yang LC, Li J, Xu SF, Cai J, Lei H, Liu DM, et al. L-3-n-butylphthalide promotes neurogenesis and neuroplasticity in cerebral ischemic rats. CNS Neurosci Ther. 2015;21:733–41. Feng X, Peng Y, Liu M, Cui L. Dl-3-n-butylphthalide extends survival by attenuating glial activation in a mouse model of amyotrophic lateral sclerosis. Neuropharmacology. 2012;62:1004–10. Xiong N, Huang J, Chen C, Zhao Y, Zhang Z, Jia M, et al. Dl-3-n-butylphthalide, a natural antioxidant, protects dopamine neurons in rotenone models for parkinson’s disease. Neurobiol Aging. 2012;33:1777–91. He Z, Zhou Y, Lin L, Wang Q, Khor S, Mao Y, et al. Dl-3-n-butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF-κB signalling. J Cell Mol Med. 2017;21:3010–22. Choi BR, Kwon KJ, Park SH, Jeon WK, Han SH, Kim HY, et al. Alternations of septal-hippocampal system in the adult wistar rat with spatial memory impairments induced by chronic cerebral hypoperfusion. Exp Neurobiol. 2011;20:92–9. Zhang M, Hu Y, Zhang J, Zhang J. FTY720 prevents spatial memory impairment in a rat model of chronic cerebral hypoperfusion via a SIRT3-independent pathway. Front Aging Neurosci. 2020;12:593364. Zhao Y, Lee JH, Chen D, Gu X, Caslin A, Li J, et al. Dl-3-n-butylphthalide induced neuroprotection, regenerative repair, functional recovery and psychological benefits following traumatic brain injury in mice. Neurochem Int. 2017;111:82–92. Ottow MK, Klaver EJ, van der Pouw Kraan TC, Heijnen PD, Laan LC, Kringel H, et al. The helminth trichuris suis suppresses TLR4-induced inflammatory responses in human macrophages. Genes Immun. 2014;15:477–86. Kim H, Chung D. TLR4-mediated IL-12 production enhances IFN-γ and IL-1β production, which inhibits TGF-β production and promotes antibody-induced joint inflammation. Arthritis Res Ther. 2012;14(5):R210. Fang H, Wang PF, Zhou Y, Wang YC, Yang QW. Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury. J Neuroinflammation. 2013;10:27. Zhu HT, Bian C, Yuan JC, Chu WH, Xiang X, Chen F, et al. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury. J Neuroinflammation. 2014;11:59. Ahmad A, Crupi R, Campolo M, Genovese T, Esposito E, Cuzzocrea S. Absence of TLR4 reduces neurovascular unit and secondary inflammatory process after traumatic brain injury in mice. PloS one. 2013;8:e57208. Takeda K, Akira S. Tlr signaling pathways. Semin Immunol. 2004;16:3–9. Zheng Y, Zhang J, Zhao Y, Zhang Y, Zhang X, Guan J, et al. Curcumin protects against cognitive impairments in a rat model of chronic cerebral hypoperfusion combined with diabetes mellitus by suppressing neuroinflammation, apoptosis, and pyroptosis. Int Immunopharmacol. 2021;93:107422. Article / Publication DetailsFirst-Page Preview
Received: May 21, 2021
Accepted: January 15, 2022
Published online: March 29, 2023
Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0
ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)
For additional information: https://www.karger.com/NPS
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