Table 2 Animal studies on the effects of extracranial injury on TBI
From: The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome
Author | Subjects | Major Relevant Findings | Limitations |
|---|---|---|---|
Yang et al., 2016 | Male C57BL/6 mice. 12–14 weeks old Sham: Incisions etc., no trauma TBI: CCI (open skull, 4.5 m/s, penetration depth 1 mm) MT: TBI + FX (Tibia, intramedullary pin) MT treated: TBI+ HMGB1 (10mg/kg 60 min prior to FX) | –Elevated brain levels of IL-6 at 2- and 4-days in MT mice compared to TBI mice, higher levels of TNF-α and IL-1β levels at 4 days. –Brain lesion volume and edema elevated in MT mice compared to TBI mice at 4 days –MT mice pre-treated with HMGB1 had reduced neurological scores, edema and brain lesion volumes at 2 and 4 days | –No FX only group: FX affect neurological scores? –No neuroinflammation analysis following HMGB1 treatment –Acute analysis only –Confounding craniotomy |
Shultz et al., 2015 | 124 male C57BL/6 mice. 12 weeks old Sham: Incisions etc., no trauma TBI: Weight-drop (333 g rod, 2 cm drop) FX: Tibia (intramedullary pin) MT: TBI + FX | –Brain IL-1β levels higher in MT group compared to all groups at 24 h and 35 days, GFAP elevated in MT mice at 24 h and 35 days, neutrophil highest in MT mice at 24 h –Edema and blood–brain barrier damage higher in MT group compared to all groups at 24 h –Lateral ventricle enlargement and diffusion abnormalities in MT mice not found other groups at 35 days –Altered anxiety-related behavior in MT mice compared to all groups at 35 days | - Variability in serum cytokine levels –No chronic time-point |
Weckbach et al., 2013 | Male C57BL/6 mice. 8–9 weeks old. Sham: Incisions etc., no trauma Blunt chest trauma (ChT): Blast wave to thorax TBI: Weight-drop (333 g rod, 2 cm drop) FX: Femur (intramedullary pin) with soft tissue injury MT (3 groups): TBI + ChT or FX + ChT or TBI + FX PT: TBI + ChT + FX | –Serum IL-6 higher in PT mice compared to all other groups at 2 h, only elevated in PT and MT mice involving TBI at 6 h –Serum G-CSF and CCL-2 higher in MT mice with TBI than for TBI only mice –Serum neutrophil apoptosis marker expression decreased in PT animals only | –Only acute time-point analysis –Systemic analysis only |
Probst et al., 2012 | 45 male C57BL/6 mice. 8–10 weeks old. TBI: Weight-drop (3m/s; weight details not included) FX/Shock: Femur (wood splint) + 60% blood vol. loss PT: TBI + FX/Shock | –Mortality rates higher in PT compared to FX/Shock and TBI only –Serum IL-6, TNF-α and CCL-2 higher in PT animals compared to FX/Shock and TBI only animals at 4 days | –No sham/control animals –Single time-point –Systemic analysis only |
Weckbach et al., 2012 | 352 male Wistar rats, 10–12 weeks old Sham: Incisions etc., no trauma Blunt chest trauma (ChT): Blast wave to thorax TBI: Weight-drop (severity not disclosed) FX: Tibia-fibula (fixation not disclosed) + soft tissue injury MT (2 groups): TBI + ChT or ChT + FX PT: TBI + ChT + FX | –Serum IL-6 singificantly increased in PT animals only –Serum neutrophil chemoattractant expression elevated only in multiply injured animals –No changes in serum TNF-α | –Only acute time-point analysis –No FX only group –Variability in serum cytokine levels –Systemic analysis only |
Mirzayan et al., 2012 | 60 male C57BL/6 mice. 8–10 weeks old. TBI: CCI (open skull, 3 m/s, penetration depth 1 mm) FX/Shock: Femur (un-supported) + 60% blood vol. loss PT: CCI + FX/Shock | –Trend (p = 0.068) towards elevated reactive astrocyte (GFAP) density in the ipsilateral hippocampus of PT compared to TBI only mice at 4 days | –No sham animals (only controls)- –Single time-point analysis |
Maegele et al., 2007 | 100 male Sprague–Dawley rats, 300–250g Control: No trauma TBI: LFP (2.1 atm) FX: Tibia (un-supported) MT: TBI + FX | –Serum IL-6 and IL-10 levels higher in MT rats compared TBI only and FX only rats during first week post-injury –No differences in serum tumour necrosis factor receptor 1 and IL-1β between groups | –Small numbers per group for plasma analysis (3–5) –No sham animals (only controls) –Systemic analysis only –Confounding craniotomy |