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Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Subacute proteome changes following traumatic injury of the developing brain: Implications for a dysregulation of
Angela M Kaindl1, Claus Zabel, Vanya Stefovska
1Department of Pediatric Neurology, Charité, University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany; Institute of Human Genetics, Charité, University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany; Department of Pediatric Neurology, University Childrens' Hospital, Technical University Dresden, Dresden, Germany. angela.kaindl@charite.de.
Insights
Traumatic brain injury (TBI) in young mice disrupts brain proteome, causing cell death, inflammation, and oxidative stress. These changes impact crucial developmental processes like neuronal migration and growth.
Area of Science:
- Neuroscience
- Developmental Biology
- Proteomics
Background:
- Traumatic brain injury (TBI) is a significant cause of death and disability in children and adolescents.
- Understanding TBI's impact on the developing brain is critical for improving outcomes.
Purpose of the Study:
- To investigate subacute proteome alterations in the developing mouse brain following traumatic brain injury (TBI).
- To identify specific proteins and pathways affected by TBI during critical developmental periods.
Main Methods:
- Utilized a percussion head trauma model in P7 mice.
- Analyzed brain proteome changes ipsilateral and contralateral to the injury site using quantitative proteomics.
- Correlated proteomic findings with histological and biochemical assessments.
Main Results:
- Identified reproducible changes in 28 proteins (30 spots) in response to TBI.
- Observed evidence of apoptosis, inflammation, and oxidative stress, including increased protein carbonyls and microglia activation.
- Detected alterations in proteins regulating neuronal migration, axonal growth, and dendritic guidance.
Conclusions:
- TBI in early development induces significant proteomic changes indicative of neurodegeneration and inflammation.
- These injuries interfere with fundamental developmental processes, potentially leading to long-term neurological deficits.
Abstract:
Traumatic brain injury (TBI) is a major cause of morbidity and mortality among children and adolescents. To gain insight into developmental events influenced by TBI, we analyzed subacute mouse brain proteome changes in a percussion head trauma model at P7 ipsi- and contralateral to the site of injury. The comparison of brain proteomes of trauma mice and controls revealed reproducible changes in the intensity of 28 proteins (30 protein spots) in response to trauma. The changes detected suggest that TBI leads to apoptosis, inflammation, and oxidative stress. These changes were consistent with our results of histological and biochemical evaluation of the brains which revealed widespread apoptotic neurodegeneration, microglia activation, and increased levels of protein carbonyls. Furthermore, we detected changes in proteins involved in neuronal migration as well as axonal and dendritic growth and guidance, suggesting interference of trauma with these developmental events.
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