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Review
. 2021 Oct:142:112079.
doi: 10.1016/j.biopha.2021.112079. Epub 2021 Aug 27.

Drosophila as a model to explore secondary injury cascades after traumatic brain injury

Lori M Buhlman  1 , Gokul Krishna  2 , T Bucky Jones  3 , Theresa Currier Thomas  4
Affiliations
Review

Drosophila as a model to explore secondary injury cascades after traumatic brain injury

Lori M Buhlman et al. Biomed Pharmacother. 2021 Oct.

Abstract

Drosophilae are emerging as a valuable model to study traumatic brain injury (TBI)-induced secondary injury cascades that drive persisting neuroinflammation and neurodegenerative pathology that imposes significant risk for long-term neurological deficits. As in mammals, TBI in Drosophila triggers axonal injury, metabolic crisis, oxidative stress, and a robust innate immune response. Subsequent neurodegeneration stresses quality control systems and perpetuates an environment for neuroprotection, regeneration, and delayed cell death via highly conserved cell signaling pathways. Fly injury models continue to be developed and validated for both whole-body and head-specific injury to isolate, evaluate, and modulate these parallel pathways. In conjunction with powerful genetic tools, the ability for longitudinal evaluation, and associated neurological deficits that can be tested with established behavioral tasks, Drosophilae are an attractive model to explore secondary injury cascades and therapeutic intervention after TBI. Here, we review similarities and differences between mammalian and fly pathophysiology and highlight strategies for their use in translational neurotrauma research.

Keywords: Apoptosis; Drosophila; Inflammation; Innate immunity; Mitochondria; Neurodegeneration; Oxidative stress; Secondary injury; Traumatic brain injury.

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Conflict of interest statement

Competing financial interests: The authors declare no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Changes in TBI pathophysiological biomarkers over time post-injury. Graphs are not representative of actual fold changes (modified from Bramlett and Dietrich, 2015 and Simon et al., 2017) (31, 32). Created with BioRender.com
Figure 2.
Figure 2.
Immune signaling pathways in Drosophila that are activated in response to CNS injury. The red line indicates negative interactions between the indicated pathways. Created with BioRender.com
Figure 3.
Figure 3.. Intrinsic apoptosis in Drosophila.
The scheme above depicts interactions of Drosophila apoptosis players and their mammalian (in grey font) orthologs and homologs. Dashed arrow (⇢) indicates translocation. Created with BioRender.com
Figure 4.
Figure 4.
Phenotypic similarity of mammalian/vertebrate and Drosophila acute response to diffuse TBI. Created with BioRender.com
Figure 5.
Figure 5.
TBI-induced Drosophila phenotypes. Sham and injured flies are shown trapped in the end of a standard food vial as part of a HIT device. Normal upright positioning and wing placement are depicted in uninjured flies (left). After TBI, Drosophila can become incapacitated, inverted, and their wings splayed (right, black arrows).
Figure 6.
Figure 6.
Summary of findings from fly TBI studies to elucidate injury models, secondary injury mechanisms, systemic changes, sex differences, and behaviors (220-223). Created with BioRender.com
See this image and copyright information in PMC

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