Linking severe traumatic brain injury to pulmonary Infections: Translocation of intestinal bacteria mediated by nociceptor neurons.

The prevalence of bacterial infections significantly increases among patients with severe traumatic brain injury (STBI), leading to a notable rise in mortality rates. While immune dysfunctions are linked to the incidence of pneumonia, our observations indicate that endogenous pathogens manifest in the lungs post-STBI due to the migration of gut commensal bacteria. This translocation involves gut-innervating nociceptor sensory neurons, which are crucial for host defense. Following STBI, the expression of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons significantly decreases, despite an initial brief increase. The timing of TRPV1 defects coincides with the occurrence of pulmonary infections post-STBI. This alteration in TRPV1+ neurons diminishes their ability to signal bacterial injuries, weakens defense mechanisms against intestinal bacteria, and increases susceptibility to pulmonary infections via bacterial translocation. Experimental evidence demonstrates that pulmonary infections can be successfully replicated through the chemical ablation and gene interference of TRPV1+ nociceptors, and that these infections can be mitigated by TRPV1 activation, thereby confirming the crucial role of nociceptor neurons in controlling intestinal bacterial migration. Furthermore, TRPV1+ nociceptors regulate the immune response of microfold cells by releasing calcitonin gene-related peptide (CGRP), thereby influencing the translocation of gut bacteria to the lungs. Our study elucidates how changes in nociceptive neurons post-STBI impact intestinal pathogen defense. This new understanding of endogenous risk factors within STBI pathology offers novel insights for preventing and treating pulmonary infections.

Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

CONTEXT: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown. OBJECTIVE: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever. MATERIALS AND METHODS: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP. RESULTS: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1ß levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats. CONCLUSIONS: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

Lizhong decoction ameliorates pulmonary infection secondary to severe traumatic brain injury in rats by regulating the intestinal physical barrier and immune response.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathogenesis of pulmonary infection secondary to severe traumatic brain injury (sTBI) is closely related to damage to the intestinal barrier. Lizhong decoction (LZD) is a prominent traditional Chinese medicine (TCM) that is widely used in clinical treatment to regulate gastrointestinal movement and enhance resistance. Nevertheless, the role and mechanism of LZD in lung infection secondary to sTBI have yet to be elucidated. AIM OF THE STUDY: Here, we evaluate the therapeutic effect of LZD on pulmonary infection secondary to sTBI in rats and discuss potential regulatory mechanisms. MATERIALS AND METHODS: The chemical constituents of LZD were analyzed by ultra-high performance liquid chromatography-Q Exactive-tandem mass spectrometry(UPLC-QE-MS/MS). The efficacy of LZD on rats with lung infection secondary to sTBI was examined by changes in brain morphology, coma time, brain water content, mNSS score, colony counts, 16S rRNA/RNaseP/MRP30 kDa(16S/RPP30), myeloperoxidase (MPO) content and pathology of lung tissue. The concentration of fluorescein isothiocyanate(FITC)-dextran in serum and the contents of secretory immunoglobulin A (SIgA) in colon tissue were detected by enzyme-linked immunosorbent assay (ELISA). Subsequently, Alcian Blue Periodic acid Schiff (AB-PAS) was used to detect colonic goblet cells. Immunofluorescence (IF) was used to detect the expression of tight junction proteins. The proportions of CD3+ cell, CD4+CD8+ T cells, CD45+ cell and CD103+ cells in the colon were analyzed by flow cytometry (FC). In addition, colon transcriptomics were analyzed by Illumina mRNA-Seq sequencing. Real-time quantitative polymerase chain reaction (qRT‒PCR) was used to verify the genes associated with LZD alleviation of intestinal barrier function. RESULTS: Twenty-nine chemical constituents of LZD were revealed with UPLC-QE-MS/MS analysis. Administration of LZD significantly reduced colony counts, 16S/RPP30 and MPO content in lung infection secondary to sTBI rats. In addition, LZD also reduced the serum FITC-glucan content and the SIgA content of the colon. Additionally, LZD significantly increased the number of colonic goblet cells and the expression of tight junction proteins. Furthermore, LZD significantly decreased the proportion of CD3+ cell, CD4+CD8+ T cells,CD45+ and CD103+ cells in colon tissue. Transcriptomic analysis identified 22 upregulated genes and 56 downregulated genes in sTBI compared to the sham group. The levels of seven genes were recovered after LZD treatment. qRT‒PCR successfully validated two genes (Jchain and IL-6) at the mRNA level. CONCLUSION: LZD can improves sTBI secondary lung infection by regulating the intestinal physical barrier and immune response. Thees results suggested that LZD may be a prospective treatment for pulmonary infection secondary to sTBI.