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

• Published in: Journal of the mechanical behavior of biomedical materials 2021-02, Vol.114, p.104176-104176, Article 104176
• Main Authors: Tsui, Christopher T., MacGillivray, Samantha R., Weber, Savannah M., McAllister, Lowell, Churchward, Matthew A., Dennison, Christopher R., Todd, Kathryn G.
• Format: Article
• Language: English
• Subjects: 3D cell culture; Biomechanical Phenomena; Brain Concussion; Cell Culture Techniques; Glia; Humans; Hydrogel; Hydrogels; Microglia; mTBI; Rotational kinematics
• ISSN: 1751-6161; 1878-0180
• DOI: 10.1016/j.jmbbm.2020.104176

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. [Display omitted] •3D hydrogel cell cultures can be utilized to study the effects of mTBI in vitro.•A device that inflicts rotational impacts onto 3D glial cell cultures was designed.•Glial cells alone do not activate in response to rotational impacts.•Neuronal damage hypothesized to be necessary for glia to activate.