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Updated: Sep 8, 2025
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Rowan O Brothers1, Sara Bitarafan2, Alyssa F Pybus3
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University.
Abstract:
Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional deficits. Numerous studies by our group and others have shown that mTBI stimulates cytokine expression and activates microglia, decreases cerebral blood flow and metabolism, and impairs cerebrovascular reactivity. Moreover, several works have reported an association between derangements in these neuroinflammatory and hemodynamic markers and cognitive impairments. Herein we detail methods to characterize the neuroinflammatory and hemodynamic tissue response to mTBI in mice. Specifically, we describe how to perform a weight-drop model of mTBI, how to longitudinally measure cerebral blood flow using a non-invasive optical technique called diffuse correlation spectroscopy, and how to perform a Luminex multiplexed immunoassay on brain tissue samples to quantify cytokines and immunomodulatory phospho-proteins (e.g., within the MAPK and NFκB pathways) that respond to and regulate activity of microglia and other neural immune cells. Finally, we detail how to integrate these data using a multivariate systems analysis approach to understand the relationships between all of these variables. Understanding the relationships between these physiologic and molecular variables will ultimately enable us to identify mechanisms responsible for mTBI.
Insights
Mild traumatic brain injuries (mTBIs) cause lasting deficits by altering brain inflammation and blood flow. This study details methods to measure these changes and their links to cognitive impairments, aiding in understanding mTBI mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Physiology
Background:
- Mild traumatic brain injuries (mTBIs) are a major public health concern with potential for cumulative, long-term functional deficits.
- mTBIs are known to trigger neuroinflammation, microglial activation, and hemodynamic changes, which have been linked to cognitive impairments.
Purpose of the Study:
- To establish comprehensive methods for characterizing the neuroinflammatory and hemodynamic responses to mTBI in a mouse model.
- To investigate the relationships between neuroinflammatory markers, hemodynamic changes, and cognitive outcomes following mTBI.
Main Methods:
- Utilized a weight-drop model to induce mTBI in mice.
- Employed diffuse correlation spectroscopy (DCS) for longitudinal, non-invasive measurement of cerebral blood flow.
- Performed Luminex multiplexed immunoassay on brain tissue to quantify cytokines and phospho-proteins involved in neuroinflammation.
- Applied multivariate systems analysis to integrate diverse physiological and molecular data.
Main Results:
- Established a robust methodology for assessing mTBI-induced changes in neuroinflammation and cerebral hemodynamics.
- Demonstrated the feasibility of longitudinally tracking hemodynamic alterations post-mTBI.
- Quantified specific cytokine and signaling pathway (MAPK, NFκB) changes associated with microglial activation.
Conclusions:
- The integrated approach provides a framework for understanding the complex interplay between neuroinflammation, hemodynamics, and functional deficits after mTBI.
- This methodology will facilitate the identification of key mechanisms underlying mTBI pathology and inform the development of targeted therapeutic strategies.
