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Published on: June 18, 2021
Mechanism of subdural effusion evolves into chronic subdural hematoma: IL-8 inducing neutrophil oxidative burst
Zhiqiang Tao1, Yingying Lin2, Maotong Hu1
1Department of Neurosurgery, Yiwu Central Hospital, Wenzhou Medical College, Yiwu 32200, Zhejiang Province, People's Republic of China.
Insights
Interleukin-8 (IL-8) drives neutrophil activity, causing fluid accumulation in subdural effusion to develop into chronic subdural hematoma (CSDH). This discovery offers new therapeutic targets for CSDH.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Chronic subdural hematoma (CSDH) remains poorly understood despite effective neurosurgical treatments.
- The correlation between subdural effusion (SDE) and CSDH is observed, but a systematic explanation for CSDH's origin and progression is lacking.
Purpose of the Study:
- To propose a novel hypothesis on the origin and progression of CSDH.
- To elucidate the role of Interleukin-8 (IL-8) in the evolution of SDE to CSDH.
Main Methods:
- This study presents a hypothesis based on existing clinical observations and known biological mechanisms.
- The proposed mechanism involves IL-8, neutrophil respiratory burst, and neo-vascularization within the subdural space.
Main Results:
- IL-8 accumulation in SDE promotes neo-vasculature formation and attracts lymphocytes.
- Neutrophil activation by IL-8 leads to neo-capillary leakage, causing plasma and blood cells to enter the SDE.
- Erythrocytes binding IL-8 creates a negative feedback loop, but this can be overwhelmed in conditions like brain atrophy, leading to hematoma expansion.
Conclusions:
- IL-8-induced neutrophil oxidative burst is a critical factor in SDE evolving into CSDH.
- Targeting IL-8 with antagonists or anti-inflammatory drugs may offer therapeutic strategies to prevent CSDH expansion.
Abstract:
Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo-vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist the liquid cavity expanding as actually occurs obvious bleeding soon.
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