4.6 Article

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

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ELSEVIER
DOI: 10.1016/j.jmbbm.2020.104176

Keywords

mTBI; Glia; Hydrogel; 3D cell culture; Rotational kinematics

Funding

  1. Alberta Health Services
  2. Natural Sciences and Engineering Research Council of Canada (NSERC)
  3. Canada Foundation for Innovation
  4. Davey Endowment for Brain Research
  5. Leaders Opportunity Fund

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The study aimed to investigate the impact of rotational kinematics on glial cells in a 3D mixed glia environment in an in vitro model. However, the results showed that rotation of glia alone did not cause activation, and future research will focus on investigating the effect of neuronal contributions in activating glia.
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.

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