TABLE 1.
Summary of the selected articles on non‐mammalian TBI models
| Animal model | Scientific name (strain) (age) | Injury model | Functional findings | Pathophysiological outcomes | Limitations of the model described | References |
|---|---|---|---|---|---|---|
| Roundworm | Caenorhabditis elegans (Wild type N2) | Therapeutic shock wave device |
Dose‐dependent reduction in mean speed of worm movement Dose‐dependent increase in percentage of worms rendered paralyzed |
Not applicable | Strains raised in different agar plates exhibited different speed of movement and the heterogeneity of the worms at baseline | Angstman et al. 20 |
|
Caenorhabditis elegans (Wild type N2) (Mutant type DR26 daf‐16(m26) (Mutant type CB1370 daf‐2(e1370) |
Therapeutic shock wave device |
Reduction of lifespan after the shockwave seen with all the strains NGM agar plates worms exhibited shorter lifespan with 500 shock wave compared to 100 shock wave Cavitation effect attenuated by PVA resulted in significant longer lifespan |
Not applicable | Not applicable | Angstman et al. 21 | |
| Caenorhabditis elegans (Wild type N2) | High‐frequency acoustic wave (SAW) | Learning delays observed at lower SAW intensity and paralysis observed at higher SAW intensity | Not applicable | Not applicable | Miansari et al. 22 | |
| Fruit fly |
Drosophila melanogaster (white (w1118) flies) (0–3 day old) |
High‐Impact trauma (HIT) |
Temporary disability and impaired movement observed Mortality increased after injury 42 fly lines showed variation in mortality (MI24) after primary injury threshold |
Innate immune response activation resembling the secondary injury mechanism Neurodegeneration seen |
Not applicable | Katzenberger et al. 23 |
|
Drosophila melanogaster (w1118 flies) (0–7 or 20–27‐day old) |
The mortality index at 24 h (MI24) after injury showed higher in older groups and genotype dependent | Not applicable | Tendency of inconsistency of unskilled person in charge in the preparation of the device will lead to inconsistent outcome | Katzenberger, Loewen, et al. 24 | ||
| Drosophila melanogaster (Genotype w1118 (BL 5905) and y1w1 (BL 1495)) |
Injury severity is proportional to the deflection angle and higher severity resulted in higher in mortality Locomotor abilities reduced after the injury but recovered to normal state at 24 h post‐TBI |
Not applicable | Not applicable | Putnam et al. 25 | ||
| Drosophila Genetic Reference Panel (DGRP) | Not applicable | Age and diet influenced the mortality through different secondary injury pathways | Not applicable | Katzenberger et al. 26 | ||
| Drosophila melanogaster (male flies that are cultured as previously described in ref. 27) | Blast simulator |
Disruption of motor function 24 h in 5 days post‐blast period and full recovery at 8 days post‐injury The lifespan and mortality of flies decreased despite the recovery of motor function |
Not applicable | Not applicable | Hockey et al. 28 | |
|
Drosophila melanogaster (Canton‐S WT female flies) (2‐day‐old) |
Blast strike |
Walking ability and distance travel after injury reduced Mobility recovered within 4 min and walking activity recovered after 2 days after 1 strike at 5.0 L/min Lifespan reduced with increase in flow rate of the strike |
Not applicable | Not applicable | Sun and Chen 29 | |
|
Drosophila melanogaster (w1118 males) (NF‐κB Relish null mutants) (RepoGal4) (UAS GFP:RpL10A) (3–7 days old) |
Drosophila Closed Head Injury (dCHI) unanesthetized |
Mortality increased dose‐dependent in 24 h after injury Negative geotaxis impaired after 5–10 consecutive hits in dose‐dependent manner Sleep pattern decreased after injury |
Innate immune response activation after injury Apoptosis seen within first 24 h |
Not applicable | van Alphen et al. 30 | |
|
Drosophila melanogaster (Canton‐S, w1118) (APPL‐Gal4) (PUAS‐Tau.wt1.13 (BL#−51362, G. Jackson)) |
Omni Bead Ruptor | Injury sensitivity increased | Innate immune system activation observed |
Risk of intestinal barrier dysfunction Confounding effect of CO2 anesthesia |
Barekat et al. 10 | |
| Zebrafish |
Danio rerio Zebrafish larvae (secA5‐YFP transgenic) (Larvae) |
Larval glutamate insult |
Dose‐dependent response to injury Locomotor deficits observed |
Not applicable | Suitable to screen for impairment or changes to the pathophysiological processes of TBI and not represent the whole disease in its entirety | McCutcheon et al. 31 |
|
Danio rerio (Transgenic Tg(coro1a:EGFP)hkz04t and Tg(HuC:EGFP)as8) (Larvae) |
Larval stab lesion | Not applicable | Microglia accumulated around the lesion after injury. | Not applicable | Gan et al. 32 | |
|
Danio rerio (wild type: WIK strain) (Larvae) |
Not applicable |
Presented different phases of primary and secondary death Excitotoxicity caused secondary cell death Microglia debris clearance suggested as neuroprotective. |
Not applicable | Herzog et al. 33 | ||
|
Danio rerio (macrophage‐specific lineage mpeg1:mCherry) (neutrophil‐specific mpo: GFP) (erythroid‐specific gata1:dsRed) (ubiq:secAnnexinV‐mVenus) (Larvae) |
Larval intracerebral hemorrhage (ICH) | Locomotor deficits increased |
Brain cell death increased Macrophage based phagocytosis observed surrounding the injury area. |
Effect of edema as seen in ICH patients might not effectively presented by this type of model due to the cranium is not fully developed. | Crilly et al. 34 | |
|
Danio rerio (wild‐type, AB strain, short fin) (adult‐ 6–12 months) |
Ultrasound Injury (pHIFU) |
Offered Non‐invasive method No contact model with behavioral endpoints assessed in an automated device. |
Molecular changes, observed which associated with the behavioral impairments |
Size ratio limitation of the pHIFU wave to only zebrafish brain Limited region‐specific analysis able for investigation limited to acute condition of the injury |
McCutcheon et al. 9 | |
| Danio rerio (Adult) | Acoustic shock wave | 50 ms shock waves at 11 MPa represented much more severe type of injury model which showed delayed recovery and displayed erratic swim patterns post‐injury. | Not applicable | Not applicable | Ferrier et al. 35 | |
|
Danio rerio (Male wild type strain AB) (older than 90 days) |
Telencephalon injury | Severe damage in tectum opticum and posterior tuberculum identified via 1325 nm 3D SD‐OCT imaging. | Not applicable | Not applicable | Zhang et al. 36 | |
|
Danio rerio (male wild type, AB strain) (adult‐ 6‐month‐old) |
Not applicable |
Telencephalon exhibited strong regenerative property after injury Proliferation activity seen highest in the brain parenchyma. |
Not applicable | Diotel et al. 37 | ||
| Danio rerio (adult 5‐ to 10‐month‐old) | Not applicable | Regenerative properties seen in the injured telencephalon. | Not applicable | Kishimoto et al. 38 | ||
|
Danio rerio (Tg(kdr:EGFP)) and wildtype) (adult−6 months old) |
Not applicable | Molecular restoration mechanism identified after injury. | Not applicable | Wu et al. 39 | ||
|
Danio rerio (Wild‐type AB strain) (adult‐ 5‐ to 8‐month old) |
Not applicable | An important biomarker for neurogenesis identified. | Not applicable | Ayari et al. 40 | ||
|
Danio rerio (Wild‐type, gol‐b1 line in the AB strain) (adult−6–10 months old) |
Not applicable |
Radial glia‐type stem/progenitor cells involved in the regeneration process after a traumatic lesion Absence of permanent glial scarring seen. |
Not applicable | Kroehne et al. 41 | ||
|
Danio rerio (Transgenic Tg(olig2:EGFP) Tg(GFAP:GFP), Tg(3.9nestin:GFP) Tg(Apo‐E‐GFP)) (adult−1–1.5‐year‐old) |
Not applicable |
Regenerative properties observed around the lesion site Oligodendrocytes increased after the lesion No permanent glial scarring observed Radial glial cells upregulated at the ventricle Moderate increase of Olig2 seen |
Not applicable | März et al. 42 | ||
| Danio rerio (adult) | Not applicable | Regenerative properties and gene upregulation seen around lesion | Side effect such as non‐specific cell ablation, higher cell death due to secondary degeneration, disruption and impairment of blood brain barrier, destruction of ventricular zone which allow CSF flow into brain parenchyma | Schmidt et al. 43 | ||
|
Danio rerio (wild‐type, AB strain) (Tg(fli1aEGFP)y1, Tg(gfap:gfp)mi2001 and Tg(olig2:gfp)) (Adult 3‐ to 4‐month old |
Not applicable |
Microglia seen as the earliest cell in the injury site Oligodendrocyte progenitor cells observed to be reduced after the injury The wound closed completely without any scar tissue |
Not applicable | Baumgart et al. 44 | ||
|
Danio rerio (Tg(1016tuba1a:GFP)) (Tg(her4.1:CreERT2)) (Tg(β‐actin2:loxP‐mCherry‐loxP‐GFP)) (Tg(gfap:GFP)) (Tg(ascl1a:GFP)) (Tg(olig2:GFP) (Double transgenic Tg(her4.1:CreERT2;β‐actin2:loxP‐mCherry‐loxP‐GFP)) |
Quinolinic acid (QA) lesion | Not applicable | Strong neural regeneration reported and the lesion repair at the telencephalon enhanced with the QA injection | Not applicable | Skaggs et al. 45 | |
|
Danio rerio (Homozygous with lofdt2, long‐fin) (Adult) |
Weight drop model | Significant deficits in spatial memory test after the injury | Gene Ontology (GO) categories of peak injury pathways and neuroregeneration pathways elucidated in the zebrafish model | Not applicable | Maheras et al. 46 | |
| Danio rerio (adult) | Brain mechanical lesion | Not applicable | Characteristics of spred‐2 in the cell proliferation phase and its role in neural repair were identified after injury | Not applicable | Lim et al. 47 |
Abbreviations: 3D SD‐OCT, three‐dimensional spectral‐domain optical coherence tomography; CO2, carbon dioxide; GO, gene ontology; MPa, MegaPascal; ms, millisecond; nm, nanometer; Olig2, Oligodendrocyte transcription factor; OPC, oligodendrocyte progenitors; pHIFU, Pulsed high‐intensity focused ultrasound; SAW, surface acoustic wave.