Department of Histology-Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.
Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Folia Neuropathol. 2024;62(3):277-292. doi: 10.5114/fn.2024.140788.
Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide, and brings a huge burden on the quality of life of patients with TBI and the country's healthcare system. Peripheral organs, especially the kidney, and liver, may be affected by the onset of molecular responses following brain tissue damage. While secondary injury responses post TBI has been well studied in the brain, the effect/consequences of these responses in the peripheral organs have not yet been fully elucidated. Thus, our study aimed to investigate the immunoreactivity of these responses, particularly via proinflammatory cytokines and autophagy markers in the kidney and liver post-acute and chronic TBI.
Mild TBI (mTBI) and repetitive mTBI (r-mTBI) were induced in male and female 2-month-old Balb/c mice via the Marmarou weight-drop model. Liver and kidney tissues were sampled at 24 hours (acute) and 30 days (chronic) post TBI and subjected to histopathological and immunoreactivity analysis.
Interleukin (IL)-6 levels were significantly increased in the male liver and kidney tissues in both TBI groups compared to the control group but were seen to be decreased in the female r-mTBI chronic liver and r-mTBI acute kidney. Tumor necrosis factor a (TNF-a) levels were found to increase only in the female r-mTBI chronic kidney tissue and mTBI chronic liver tissue. IL-1b levels were increased in the male and female r-mTBI liver tissues but decreased in the female mTBI kidney tissue. Inducible nitric oxide synthase (iNOS) levels were found to be significantly increased in the female mTBI acute and r-mTBI chronic kidney tissue and mTBI liver tissue, but decreased in the r-mTBI acute kidney and r-mTBI liver tissues. Beclin-1 levels were increased in male mTBI chronic and r-mTBI acute liver tissue but decreased in the r-mTBI chronic group. LC3A/B and P62/SQSTM1 levels were significantly increased in the female mTBI chronic and male r-mTBI chronic liver tissues but decreased in the male r-mTBI and female r-mTBI acute kidney tissues. Significant histopathological changes were also observed in the liver and kidney tissue which were dependent on the TBI severity, gender, and time post TBI.
The results showed that TBI may elicit peripheral molecular responses, particularly in terms of alteration in the levels of inflammatory cytokines and autophagy markers, which were gender- and time-dependent. This suggests that TBI may have a significant role in the cellular damage of the kidney and liver in both the acute and chronic phases post TBI, thus ensuring that the effects of TBI may not be confined to the brain.
颅脑损伤（TBI）是全球范围内导致死亡和残疾的主要原因之一，给 TBI 患者的生活质量和国家医疗体系带来了巨大负担。脑组织损伤后，外周器官（尤其是肾脏和肝脏）可能会受到分子反应的影响。虽然 TBI 后的继发性损伤反应在大脑中已经得到了很好的研究，但这些反应在周围器官中的影响/后果尚未得到充分阐明。因此，我们的研究旨在研究这些反应的免疫反应性，特别是通过急性和慢性 TBI 后肾脏和肝脏中的促炎细胞因子和自噬标志物来研究。
通过 Marmarou 重物坠落模型诱导雄性和雌性 2 个月大的 Balb/c 小鼠发生轻度 TBI（mTBI）和重复 mTBI（r-mTBI）。TBI 后 24 小时（急性）和 30 天（慢性）采集肝脏和肾脏组织，进行组织病理学和免疫反应性分析。
与对照组相比，TBI 组雄性肝脏和肾脏组织中的白细胞介素（IL）-6 水平显著升高，但 r-mTBI 慢性肝脏和 r-mTBI 急性肾脏中的 IL-6 水平降低。仅在女性 r-mTBI 慢性肾脏组织和 mTBI 慢性肝脏组织中发现肿瘤坏死因子-α（TNF-α）水平升高。IL-1b 水平在雄性和雌性 r-mTBI 肝脏组织中升高，但在雌性 mTBI 肾脏组织中降低。诱导型一氧化氮合酶（iNOS）水平在雌性 mTBI 急性和 r-mTBI 慢性肾脏组织以及 mTBI 肝脏组织中显著升高，但在 r-mTBI 急性肾脏和 r-mTBI 肝脏组织中降低。Beclin-1 水平在雄性 mTBI 慢性和 r-mTBI 急性肝脏组织中升高，但在 r-mTBI 慢性组中降低。LC3A/B 和 P62/SQSTM1 水平在女性 mTBI 慢性和男性 r-mTBI 慢性肝脏组织中显著升高，但在男性 r-mTBI 和女性 r-mTBI 急性肾脏组织中降低。在肝组织和肾组织中也观察到了显著的组织病理学变化，这些变化取决于 TBI 的严重程度、性别和 TBI 后时间。
结果表明，TBI 可能会引起外周分子反应，特别是在炎症细胞因子和自噬标志物水平的改变方面，这些反应具有性别和时间依赖性。这表明，TBI 可能在 TBI 后急性和慢性阶段对肾脏和肝脏的细胞损伤有重要作用，因此 TBI 的影响可能不仅局限于大脑。
