Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and has complicated underlying pathophysiology. Numerous TBI animal models have been developed over the past decade to effectively mimic the human TBI pathophysiology. These models are of mostly mammalian origin including rodents and non‐human primates. However, the mammalian models demanded higher costs and have lower throughput often limiting the progress in TBI research. Thus, this systematic review aims to discuss the potential benefits of non‐mammalian TBI models in terms of their face validity in resembling human TBI. Three databases were searched as follows: PubMed, Scopus, and Embase, for original articles relating to non‐mammalian TBI models, published between January 2010 and December 2019. A total of 29 articles were selected based on PRISMA model for critical appraisal. Zebrafish, both larvae and adult, was found to be the most utilized non‐mammalian TBI model in the current literature, followed by the fruit fly and roundworm. In conclusion, non‐mammalian TBI models have advantages over mammalian models especially for rapid, cost‐effective, and reproducible screening of effective treatment strategies and provide an opportunity to expedite the advancement of TBI research.

Highlights

  • Traumatic brain injury (TBI) is one of the leading causes of death and morbidity worldwide especially in industrialized countries.[1]

  • After applying the inclusion and exclusion criteria, a total of 240 articles were excluded which included; (a) 56 articles not published within the specified date range (1st January 2010 – 31st December 2019), (b) 117 non-original research articles, (c) 38 duplicates, and (d) 29 articles that were not related to non-mammalian animal models of traumatic brain injury (Figure 1)

  • Caenorhabditis worm (C. elegans) is one of the least used alternate choices of animal models in TBI research (Table 1) despite the advantages it offers including the relative ease of genetic manipulation.[20]

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Summary

Introduction

Traumatic brain injury (TBI) is one of the leading causes of death and morbidity worldwide especially in industrialized countries.[1] TBI has become a major public health concern with a global prevalence that has escalated to almost 27.08 million people in 2016 as reported by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) study.[2] The study stated that about 8.1 million people were living with long-term disability caused by TBI, mainly due to falls and motor vehicle accidents. Traumatic brain injury has been alarmingly related to a number of adverse long-term effects, including elevated risk toward long-term complications such as Parkinson's disease, Alzheimer's disease, Dementia Pugilistica, and posttraumatic epilepsy.[3] TBI is comprised of two phases which are the primary and secondary injury phase. The primary injury phase is the initial impact encountered from the external mechanical force that results in blood vessel damage, axonal tearing,[4] cell death at the injury site, blood-brain barrier disruption, presence of edema, and generation of damage-associated molecular patterns (DAMPs).[5]

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