TY - JOUR
T1 - A novel animal model of closed-head concussive-induced mild traumatic brain injury
T2 - Development, implementation, and characterization
AU - Chen, Zhiyong
AU - Leung, Lai Yee
AU - Mountney, Andrea
AU - Liao, Zhilin
AU - Yang, Weihong
AU - Lu, Xi Chun May
AU - Dave, Jitendra
AU - Deng-Bryant, Ying
AU - Wei, Guo
AU - Schmid, Kara
AU - Shear, Deborah A.
AU - Tortella, Frank C.
PY - 2012/1/20
Y1 - 2012/1/20
N2 - 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 24h 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.
AB - 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 24h 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.
KW - biomarker
KW - brain injury
KW - closed-head injury
KW - concussion; mild traumatic projectile concussive impact
KW - motor function
KW - rat helmet
UR - http://www.scopus.com/inward/record.url?scp=84863069049&partnerID=8YFLogxK
U2 - 10.1089/neu.2011.2057
DO - 10.1089/neu.2011.2057
M3 - Article
C2 - 21988140
AN - SCOPUS:84863069049
SN - 0897-7151
VL - 29
SP - 268
EP - 280
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 2
ER -