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Traumatic Brain Injury-Mediated Neuroinflammation and Neurological Deficits are Improved by 8-Methoxypsoralen Through Modulating PPARγ/NF-κB Pathway

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Abstract

8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in-vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats’ neurological functions. The rats’ brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl’s staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.

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Data Availability

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not- for- profit sectors.

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  1. Yuzuo Hui1 and Han Zhao have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Liaocheng People’s Hospital, 67 Dongchang Road, Liaocheng, 252000, Shandong, China

    Yuzuo Hui & Haitao Zhang

  2. Department of Neurosurgery, Taian Central Hospital, Taian, 271000, Shandong, China

    Han Zhao

  3. Shandong Rongjun General Hospital, Ward 7, Jinan, 250000, Shandong, China

    Lei Shi

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  1. Yuzuo Hui
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Contributions

Conceived and designed the experiments: HZ. Performed the experiments: YH, HZ. Statistical analysis: LS. Wrote the paper: YH, HZ. All authors read and approved the final manuscript.

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Correspondence to Haitao Zhang.

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Our study was approved by the ethic committee of Liaocheng People’s Hospital (Approve No: LC-H2019039).

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The analysis result of F, df and P-values for the ANOVA factors and interactions in Figs. 4, 5 and 6

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Hui, Y., Zhao, H., Shi, L. et al. Traumatic Brain Injury-Mediated Neuroinflammation and Neurological Deficits are Improved by 8-Methoxypsoralen Through Modulating PPARγ/NF-κB Pathway. Neurochem Res 48, 625–640 (2023). https://doi.org/10.1007/s11064-022-03788-6

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