Increased severity of the CHIMERA model induces acute vascular injury, sub-acute deficits in memory recall, and chronic white matter gliosis

被引:33
作者
Bashir, Asma [1 ,2 ]
Abebe, Zelalem A. [3 ,4 ]
McInnes, Kurt A. [3 ,4 ]
Button, Emily B. [1 ]
Tatarnikov, Igor [2 ,5 ]
Cheng, Wai Hang [1 ]
Haber, Margalit [6 ]
Wilkinson, Anna [1 ]
Barron, Carlos [1 ]
Diaz-Arrastia, Ramon [6 ]
Stukas, Sophie [1 ]
Cripton, Peter A. [3 ,4 ]
Wellington, Cheryl L. [1 ]
机构
[1] Univ British Columbia, Dept Pathol & Lab Med, Djavad Mowafaghian Ctr Brain Hlth, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Grad Program Neurosci, 2215 Wesbrook Mak, Vancouver, BC V6T 1Z3, Canada
[3] Univ British Columbia, Dept Mech Engn, Int Ctr Repair Discoveries, Vancouver, BC V5Z 1M9, Canada
[4] Univ British Columbia, Sch Biomed Engn, Vancouver, BC V5Z 1M9, Canada
[5] Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
[6] Univ Penn, Dept Neurol, 51 N 39th St, Philadelphia, PA 19104 USA
关键词
TBI; CHIMERA; Diffuse axonal injury; Vascular injury; Plasma biomarkers; TRAUMATIC BRAIN-INJURY; HEAD-INJURY; SEX-DIFFERENCES; PROFESSIONAL FOOTBALL; MICROVASCULAR INJURY; RISK; CONCUSSION; GENOTYPE; AGE;
D O I
10.1016/j.expneurol.2019.113116
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Traumatic brain injury (TBI) is a leading cause of death and disability in modern societies. Diffuse axonal and vascular injury are nearly universal consequences of mechanical energy impacting the head and contribute to disability throughout the injury severity spectrum. CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a non-surgical, impact-acceleration model of rodent TBI that reliably produces diffuse axonal injury characterized by white matter gliosis and axonal damage. At impact energies up to 0.7 joules, which result in mild TBI in mice, CHIMERA does not produce detectable vascular or grey matter injury. This study was designed to expand CHIMERA's capacity to induce more severe injuries, including vascular damage and grey matter gliosis. This was made possible by designing a physical interface positioned between the piston and animal's head to allow higher impact energies to be transmitted to the head without causing skull fracture. Here, we assessed interface-assisted single CHIMERA TBI at 2.5 joules in wild-type mice using a study design that spanned 6 h-60 d time points. Injured animals displayed robust acute neurological deficits, elevated plasma total tau and neurofilament-light levels, transiently increased proinflammatory cytokines in brain tissue, blood-brain barrier (BBB) leakage and microstructural vascular abnormalities, and grey matter microgliosis. Memory deficits were evident at 30 d and resolved by 60 d. Intriguingly, white matter injury was not remarkable at acute time points but evolved over time, with white matter gliosis being most extensive at 60 d. Interface-assisted CHIMERA thus enables experimental modeling of distinct endophenotypes of TBI that include acute vascular and grey matter injury in addition to chronic evolution of white matter damage, similar to the natural history of human TBI.
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页数:16
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