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Purpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats. Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1ß, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3. Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS. Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.
RESUMO
BACKGROUND: Hematoma expansion (HE) is a significant predictor of poor outcomes in patients with intracerebral hemorrhage (ICH). Non-contrast computed tomography (NCCT) markers in ICH are promising predictors of HE. We aimed to determine the association of the NCCT markers with HE by using different temporal HE definitions. METHODS: We utilized Risa-MIS-ICH trial data (risk stratification and minimally invasive surgery in acute intracerebral hemorrhage). We defined four HE types based on the time to baseline CT (BCT) and the time to follow-up CT (FCT). Hematoma volume was measured by software with a semi-automatic edge detection tool. HE was defined as a follow-up CT hematoma volume increase of >6 mL or a 33% hematoma volume increase relative to the baseline CT. Multivariable regression analyses were used to determine the HE parameters. The prediction potential of indicators for HE was evaluated using receiver-operating characteristic analysis. RESULTS: The study enrolled 158 patients in total. The time to baseline CT was independently associated with HE in one type (odds ratio (OR) 0.234, 95% confidence interval (CI) 0.077-0.712, p = 0.011), and the blend sign was independently associated with HE in two types (OR, 6.203-6.985, both p < 0.05). Heterogeneous density was independently associated with HE in all types (OR, 6.465-88.445, all p < 0.05) and was the optimal type for prediction, with an area under the curve of 0.674 (p = 0.004), a sensitivity of 38.9%, and specificity of 96.0%. CONCLUSION: In specific subtypes, the time to baseline CT, blend sign, and heterogeneous density were independently associated with HE. The association between NCCT markers and HE is influenced by the temporal definition of HE. Heterogeneous density is a stable and robust predictor of HE in different subtypes of hematoma expansion.
