Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury

• Type of Material: Article
• Authors: Rowan O Brothers, Georgia Institute of Technology; Sara Bitarafan, Georgia Institute of Technology; Alyssa F Pybus, Georgia Institute of Technology; Levi B Wood, Georgia Institute of Technology; Erin Buckley, Emory University
• Language: English
• Date: 2022-05-01
• Publisher: JOURNAL OF VISUALIZED EXPERIMENTS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 JoVE Journal of Visualized Experiments
• Final Published Version (URL): http://dx.doi.org/10.3791/61504
• Title of Journal or Parent Work: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
• Volume: 2022
• Issue: 183
• Keywords: Multidisciplinary Sciences; VULNERABILITY; RECOVERY; TEMPORAL WINDOW; CONCUSSION; MODELS; DIFFUSE CORRELATION SPECTROSCOPY; CEREBRAL-BLOOD-FLOW; Science & Technology - Other Topics; Science & Technology

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.