J Korean Neurosurg Soc.  2022 Sep;65(5):680-687. 10.3340/jkns.2021.0310.

Mild Traumatic Brain Injury and Subsequent Acute Pulmonary Inflammatory Response

• Lim SH
• Jung H
• Youn DH
• Kim TY
• Han SW
• Kim BJ
• Lee JJ
• Jeon JP

• KMID: 2533030
• DOI: http://doi.org/10.3340/jkns.2021.0310

Abstract

Objective
: The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI.
Methods
: Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines.
Results
: Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were observed after mild TBI. The IL-6, TNF-α, and TGF-β levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury.
Conclusion
: Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient’s prognosis.

Keyword

Traumatic brain injury; Acute lung injury; Inflammation

Figure

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  Fig. 1. A : Schematic diagram of the experimental design of the study. B and C : The mild traumatic brain injury (TBI) model was generated using controlled cortical impact (CCI) on the right cortex by targeting a point located 2 mm lateral and 1.5 mm posterior from the bregma. qRT-PCR : quantitative real-time polymerase chain reaction.

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  Fig. 2. A : Mild traumatic injury (TBI) increased neuronal cell death seen on fluoro-Jade B (FJB) staining over time. The fluorescence images represent the relative degree of neuronal death in the cortex in sham-operated and mild TBI mice 6 hours, 24 hours, and 72 hours after the insult (scale bar=200 µm). B : Comparison of the quantification of FJB-positive cells in the cortex over time. C-F : Changes in pro-inflammatory (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) and anti-inflammatory cytokines (IL-10 and transforming growth factor [TGF]-β) in the brain over time after the insults. Error bars, mean standard error of mean. *p<0.05.

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  Fig. 3. A : Illustration of alveolar morphological changes and acute pulmonary inflammatory response over time after mild traumatic brain injury (TBI) using Astra blue and hematoxylin staining (scale bar=20 μm). The sections show mast cell infiltration (red arrows), neutrophils (yellow arrow), interstitial edema, and structural changes in the alveoli. B : Comparison of mast cell counts in the lungs over time after the insult. C-F : Changes in proinflammatory (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) and anti-inflammatory cytokines (IL-10 and transforming growth factor [TGF]-β) in the lungs over time in response to mild TBI. All slides were observed under light microscopy at ×100 original magnification. Error bars, mean standard error of mean. *p<0.05.

Reference

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