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Increased severity of the CHIMERA model induces acute vascular injury, sub-acute deficits in memory recall, and chronic white matter gliosis.
Bashir, Asma; Abebe, Zelalem A; McInnes, Kurt A; Button, Emily B; Tatarnikov, Igor; Cheng, Wai Hang; Haber, Margalit; Wilkinson, Anna; Barron, Carlos; Diaz-Arrastia, Ramon; Stukas, Sophie; Cripton, Peter A; Wellington, Cheryl L.
Afiliación
  • Bashir A; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada; Graduate Program in Neuroscience, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada. Electro
  • Abebe ZA; International Centre On Repair Discoveries, Department of Mechanical Engineering and School of Biomedical Engineering, University of British Columbia, Vancouver V5Z 1M9, BC, Canada.
  • McInnes KA; International Centre On Repair Discoveries, Department of Mechanical Engineering and School of Biomedical Engineering, University of British Columbia, Vancouver V5Z 1M9, BC, Canada.
  • Button EB; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada. Electronic address: ebbutton@mail.ubc.ca.
  • Tatarnikov I; Graduate Program in Neuroscience, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada; Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada.
  • Cheng WH; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada.
  • Haber M; Department of Neurology, University of Pennsylvania, 51 N 39th Street, Philadelphia, PA, USA.
  • Wilkinson A; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada. Electronic address: anna.wilkinson@ubc.ca.
  • Barron C; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada. Electronic address: cbe37@mail.ubc.ca.
  • Diaz-Arrastia R; Department of Neurology, University of Pennsylvania, 51 N 39th Street, Philadelphia, PA, USA. Electronic address: ramon.diaz-arrastia@uphs.upenn.edu.
  • Stukas S; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada. Electronic address: sophie.stukas@ubc.ca.
  • Cripton PA; International Centre On Repair Discoveries, Department of Mechanical Engineering and School of Biomedical Engineering, University of British Columbia, Vancouver V5Z 1M9, BC, Canada. Electronic address: cripton@mech.ubc.ca.
  • Wellington CL; Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, University of British Columbia, 2215 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada. Electronic address: wcheryl@mail.ubc.ca.
Exp Neurol ; 324: 113116, 2020 02.
Article en En | MEDLINE | ID: mdl-31734317
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recuerdo Mental / Traumatismos Cerrados de la Cabeza / Lesiones del Sistema Vascular / Sustancia Blanca / Gliosis / Trastornos de la Memoria Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Exp Neurol Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recuerdo Mental / Traumatismos Cerrados de la Cabeza / Lesiones del Sistema Vascular / Sustancia Blanca / Gliosis / Trastornos de la Memoria Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Exp Neurol Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos