Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by abnormalities in brain microstructure, neuroinflammation, and social behavior deficits. In addition, children with ASD frequently exhibit irritable bowel syndrome and other gastrointestinal symptoms linked to anxiety....
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Elsevier
2025-08-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811925003477 |
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| author | Lalitha Palanivelu You-Yin Chen Yao-Wen Liang Ssu-Ju Li Ching-Wen Chang Yu-Ting Huang Yu-Chun Lo |
| author_facet | Lalitha Palanivelu You-Yin Chen Yao-Wen Liang Ssu-Ju Li Ching-Wen Chang Yu-Ting Huang Yu-Chun Lo |
| author_sort | Lalitha Palanivelu |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by abnormalities in brain microstructure, neuroinflammation, and social behavior deficits. In addition, children with ASD frequently exhibit irritable bowel syndrome and other gastrointestinal symptoms linked to anxiety. This study investigated if central thalamic nucleus deep brain stimulation (CTN-DBS) can improve social behavior, suppress neuroinflammation, restore brain microstructure, and reverse gut dysbiosis in the valproic acid-induced rat model of ASD by modulating the microbiota–gut–brain (MGB) axis. Daily CTN-DBS for 7 days (30 min/day) enhanced neuronal density, organization, and microstructural complexity as evidenced by increases in the diffusion kurtosis imaging (DKI) metrics—mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK). These neurostructural improvements were associated with reduced astrocyte and microglial activation, two core hallmarks of neuroinflammation in ASD, and lower systemic levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, signaling factors that may increase gut permeability and disrupt gut microbial composition. Indeed, CTN-DBS enhanced gut barrier function, promoted the proliferation of beneficial Bacteroides spp., and improved short-chain fatty acid (SCFA) metabolism, thereby restoring normal gut acetate and butyrate levels and counteracting dysbiosis. Specific energy absorption rate and thermal effect analyses demonstrated that CTN-DBS is safe under DKI. These findings support CTN-DBS as a safe and efficacious therapeutic strategy to reduce neuroinflammation, restore gray matter circuit function, and improve gut microbial composition in ASD via MGB axis modulation. Furthermore, DKI can reveal neurobiomarkers indicative of these improvements in ASD model rats. |
| format | Article |
| id | doaj-art-9a1ea78e54e84dcc8443a6ef13e6811d |
| institution | OA Journals |
| issn | 1095-9572 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj-art-9a1ea78e54e84dcc8443a6ef13e6811d2025-08-20T02:21:59ZengElsevierNeuroImage1095-95722025-08-0131712134410.1016/j.neuroimage.2025.121344Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young ratsLalitha Palanivelu0You-Yin Chen1Yao-Wen Liang2Ssu-Ju Li3Ching-Wen Chang4Yu-Ting Huang5Yu-Chun Lo6International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, 7F., No. 250, Wuxing St., Taipei City, 11031, TaiwanDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei City, 112304, Taiwan; PhD. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University. 12F., Education and Research Building, Shuang-Ho Campus, No. 301, Yuantong Rd., New Taipei City 23564, TaiwanDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei City, 112304, TaiwanDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei City, 112304, TaiwanDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei City, 112304, TaiwanDepartment of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei City, 11031, TaiwanPhD. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University. 12F., Education and Research Building, Shuang-Ho Campus, No. 301, Yuantong Rd., New Taipei City 23564, Taiwan; Corresponding author.Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by abnormalities in brain microstructure, neuroinflammation, and social behavior deficits. In addition, children with ASD frequently exhibit irritable bowel syndrome and other gastrointestinal symptoms linked to anxiety. This study investigated if central thalamic nucleus deep brain stimulation (CTN-DBS) can improve social behavior, suppress neuroinflammation, restore brain microstructure, and reverse gut dysbiosis in the valproic acid-induced rat model of ASD by modulating the microbiota–gut–brain (MGB) axis. Daily CTN-DBS for 7 days (30 min/day) enhanced neuronal density, organization, and microstructural complexity as evidenced by increases in the diffusion kurtosis imaging (DKI) metrics—mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK). These neurostructural improvements were associated with reduced astrocyte and microglial activation, two core hallmarks of neuroinflammation in ASD, and lower systemic levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, signaling factors that may increase gut permeability and disrupt gut microbial composition. Indeed, CTN-DBS enhanced gut barrier function, promoted the proliferation of beneficial Bacteroides spp., and improved short-chain fatty acid (SCFA) metabolism, thereby restoring normal gut acetate and butyrate levels and counteracting dysbiosis. Specific energy absorption rate and thermal effect analyses demonstrated that CTN-DBS is safe under DKI. These findings support CTN-DBS as a safe and efficacious therapeutic strategy to reduce neuroinflammation, restore gray matter circuit function, and improve gut microbial composition in ASD via MGB axis modulation. Furthermore, DKI can reveal neurobiomarkers indicative of these improvements in ASD model rats.http://www.sciencedirect.com/science/article/pii/S1053811925003477Autism spectrum disorderSocial interactionCentral thalamic DBSMicrobiota–gut–brain axisNeuroinflammationDiffusion kurtosis imaging |
| spellingShingle | Lalitha Palanivelu You-Yin Chen Yao-Wen Liang Ssu-Ju Li Ching-Wen Chang Yu-Ting Huang Yu-Chun Lo Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats NeuroImage Autism spectrum disorder Social interaction Central thalamic DBS Microbiota–gut–brain axis Neuroinflammation Diffusion kurtosis imaging |
| title | Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats |
| title_full | Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats |
| title_fullStr | Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats |
| title_full_unstemmed | Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats |
| title_short | Diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation, gray matter microstructural abnormalities, and gut dysbiosis by central thalamic deep brain stimulation in autistic -like young rats |
| title_sort | diffusion kurtosis imaging biomarkers associated with amelioration of neuroinflammation gray matter microstructural abnormalities and gut dysbiosis by central thalamic deep brain stimulation in autistic like young rats |
| topic | Autism spectrum disorder Social interaction Central thalamic DBS Microbiota–gut–brain axis Neuroinflammation Diffusion kurtosis imaging |
| url | http://www.sciencedirect.com/science/article/pii/S1053811925003477 |
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