Applying a novel 3D hydrogel cell culture to investigate activation of microglia due to rotational kinematics associated with mild traumatic brain injury

Christopher T Tsui; Samantha R MacGillivray; Savannah M Weber; Lowell McAllister; Matthew A Churchward; Christopher R Dennison; Kathryn G Todd

doi:10.1016/j.jmbbm.2020.104176

Applying a novel 3D hydrogel cell culture to investigate activation of microglia due to rotational kinematics associated with mild traumatic brain injury

J Mech Behav Biomed Mater. 2021 Feb:114:104176. doi: 10.1016/j.jmbbm.2020.104176. Epub 2020 Oct 28.

Authors

Christopher T Tsui¹, Samantha R MacGillivray², Savannah M Weber³, Lowell McAllister⁴, Matthew A Churchward⁵, Christopher R Dennison⁶, Kathryn G Todd⁷

Affiliations

¹ Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2G3, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, AB T6G 2V2, Canada. Electronic address: cttsui@ualberta.ca.
² Biomedical Instrumentation Lab, Department of Mechanical Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada. Electronic address: smacgill@ualberta.ca.
³ Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2G3, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada. Electronic address: smweber@ualberta.ca.
⁴ Biomedical Instrumentation Lab, Department of Mechanical Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada. Electronic address: lowellm@ualberta.ca.
⁵ Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2G3, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada. Electronic address: churchwa@ualberta.ca.
⁶ Biomedical Instrumentation Lab, Department of Mechanical Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada. Electronic address: cdenniso@ualberta.ca.
⁷ Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2G3, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, AB T6G 2V2, Canada. Electronic address: kgtodd@ualberta.ca.

PMID: 33184015
DOI: 10.1016/j.jmbbm.2020.104176

Abstract

Many investigations on mild traumatic brain injury (mTBI) aim to further understand how cells in the brain react to the mechanical forces associated with the injury. While it is known that rapid head rotation is a mechanism contributing to mTBI, establishing definitive thresholds for head rotation has proved challenging. One way to advance determining mechanisms and thresholds for injury is through in vitro models. Here, an apparatus has been designed that is capable of delivering rotational forces to three-dimensional (3D) hydrogel cell cultures. Using an in vitro model, we test the hypothesis that rotational kinematics can activate microglia suspended in a 3-dimensional mixed glia environment (absent neurons). The impact apparatus was able to deliver peak angular velocities of approximately 45 rad/s, a magnitude for angular velocity that in select literature is associated with diffuse brain injury. However, no measurable glial cell reactivity was observed in response to the rotational kinematics through any of the chosen metrics (nitric oxide, pro-inflammatory cytokine release and proportion of amoeboid activated microglia). The results generated from this study suggest that rotation of the glia alone did not cause activation - in future work we will investigate the effect of neuronal contributions in activating glia.

Keywords: 3D cell culture; Glia; Hydrogel; Rotational kinematics; mTBI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomechanical Phenomena
Brain Concussion*
Cell Culture Techniques
Humans
Hydrogels
Microglia

Substances

Hydrogels