title: A novel animal model of closed-head concussive-induced mild traumatic brain injury: development, implementation, and characterization.
abstract: Closed-head concussive injury is one of the most common causes of traumatic brain injury (TBI). While single concussions result in short-term neurologic dysfunction, multiple concussions can result in cumulative damage and increased risk for neurodegenerative disease. Despite the prevalence of concussion, knowledge about what occurs in the brain following this injury is limited, in part due to the limited number of appropriate animal research models. To study clinically relevant concussion we recently developed a simple, non-invasive rodent model of closed-head projectile concussive impact (PCI) TBI. For this purpose, anesthetized rats were placed on a platform positioned above a torque-sealed microcentrifuge tube packed with fixed amounts of dry ice. Upon heating, rapid sublimation of the dry ice produced a build-up of compressed CO(2) that triggered an eruptive force causing the cap to launch as an intact projectile, resulting in a targeted PCI head injury. A stainless steel helmet was implemented to protect the head from bruising, yet allowing the brain to sustain a mild PCI event. Depending on the injury location and the application of the helmet, PCI-induced injuries ranged from severe (i.e., head injury with subdural hematomas, intracranial hemorrhage, and brain tissue damage), to mild (no head injury, intracranial hemorrhage, or gross morphological pathology). Although no gross pathology was evident in mild PCI-induced injury, the following protein changes and behavioral abnormalities were detected between 1 and 24 h after PCI injury: (1) upregulation of glial fibrillary acidic protein (GFAP) in hippocampal regions; (2) upregulation of ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) in cortical tissue; and (3) significant sensorimotor abnormalities. Overall, these results indicated that this PCI model was capable of replicating salient pathologies of a clinical concussion, and could generate reproducible and quantifiable outcome measures.
authors: Brain Trauma Neuroprotection and Neurorestoration, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors: Zhiyong
authors: Z
authors: Chen
authors: Lai Yee
authors: LY
authors: Leung
authors: Andrea
authors: A
authors: Mountney
authors: Zhilin
authors: Z
authors: Liao
authors: Weihong
authors: W
authors: Yang
authors: Xi-Chun May
authors: XC
authors: Lu
authors: Jitendra
authors: J
authors: Dave
authors: Ying
authors: Y
authors: Deng-Bryant
authors: Guo
authors: G
authors: Wei
authors: Kara
authors: K
authors: Schmid
authors: Deborah A
authors: DA
authors: Shear
authors: Frank C
authors: FC
authors: Tortella
mesh_terms: D000818:Animals; D001924:Brain Concussion / Q000150:complications* / Q000175:diagnosis* / Q000503:physiopathology; D001930:Brain Injuries / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D003943:Diagnostic Techniques, Neurological / Q000191:economics / Q000295:instrumentation; D004195:Disease Models, Animal; D018450:Disease Progression; D016489:Head Injuries, Closed / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009460:Neurologic Examination / Q000191:economics / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015599:Trauma Severity Indices