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Updated: Oct 18, 2025
Stab-Wound Mouse Model for Studying Hemorrhage and Inflammation in Traumatic Brain Injury
Published on: February 21, 2025
Rapid orderly migration of neutrophils after traumatic brain injury depends on MMP9/13
Dandan Zou1, Wenlong Hu1, Jie Qin1
1Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing, 400715, PR China.
Abstract:
Macrophages and granulocytes play an important role in various injuries and post-traumatic repair. Due to the limited number of neutrophils in the brain, their role in traumatic brain injury has rarely been mentioned. Here, neutrophils were found to take over the role of macrophages after brain injury in the absence of macrophages. Neutrophils have the characteristics of long residence time and number advantage to actively remove the apoptotic debris. The number of neutrophils recruited was effectively reduced by inhibiting IL-1β. Interestingly, neutrophils migrated regularly and rapidly to the wound during the early stages of brain injury through three paths. They first infiltrated the wound mainly through blood circulation around the eyes, then became unscrupulous and began to move directly across the brain. In addition, MMP9 and MMP13 were found to be related to the migration of neutrophils, and inhibition of MMP could significantly inhibit the number and speed of neutrophils' migration. Our study showed that neutrophils rely on MMP9 and MMP13 for a rapid and orderly response to brain injury to maintain central nervous system stability in the absence or decrease of macrophages.
Insights
In brain injuries lacking macrophages, neutrophils compensate by clearing debris. Inhibiting IL-1β reduces neutrophil recruitment, while MMP9 and MMP13 are key to their migration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Macrophages and granulocytes are crucial in injury repair.
- Neutrophils' role in traumatic brain injury (TBI) is understudied due to their low numbers in the brain.
Purpose of the Study:
- To investigate the role of neutrophils in TBI, particularly in scenarios with limited macrophage presence.
- To identify mechanisms regulating neutrophil recruitment and migration to the injury site.
Main Methods:
- Observational study of neutrophil behavior post-brain injury.
- Inhibition of Interleukin-1 beta (IL-1β) to assess its effect on neutrophil recruitment.
- Investigation of Matrix Metalloproteinases (MMPs), specifically MMP9 and MMP13, in neutrophil migration.
Main Results:
- Neutrophils were observed to replace macrophages in clearing apoptotic debris after brain injury.
- Inhibiting IL-1β significantly reduced the number of neutrophils recruited to the injury site.
- Neutrophil migration occurred via distinct pathways, including through ocular circulation and direct brain traversal.
- MMP9 and MMP13 were identified as critical factors mediating neutrophil migration speed and quantity.
Conclusions:
- Neutrophils play a vital compensatory role in TBI, especially when macrophages are scarce.
- Targeting IL-1β can modulate neutrophil infiltration.
- MMP9 and MMP13 are essential for efficient neutrophil response to brain injury, supporting central nervous system stability.
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