Increased severity of the CHIMERA model induces acute vascular injury, sub-acute deficits in memory recall, and chronic white matter gliosis
| Autor: | Emily B. Button, Sophie Stukas, Ramon Diaz-Arrastia, Margalit Haber, Asma Bashir, Anna Wilkinson, Kurt A. McInnes, Peter A. Cripton, Carlos Barron, Cheryl L. Wellington, Zelalem A. Abebe, Wai Hang Cheng, Igor Tatarnikov |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Rotation Traumatic brain injury Acceleration Grey matter Microgliosis Proinflammatory cytokine White matter 03 medical and health sciences Mice 0302 clinical medicine Developmental Neuroscience Skull fracture Head Injuries Closed medicine Animals Gliosis Maze Learning Swimming Brain Chemistry Memory Disorders business.industry Depression Diffuse axonal injury Vascular System Injuries medicine.disease White Matter Axons Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Neurology Cerebrovascular Circulation Mental Recall medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Experimental neurology. 324 |
| ISSN: | 1090-2430 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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