TY - JOUR
T1 - Mild closed-head injury in conscious rats causes transient neurobehavioral and glial disturbances
T2 - A novel experimental model of concussion
AU - Pham, Louise
AU - Shultz, Sandy R.
AU - Kim, Hyun Ah
AU - Brady, Rhys
AU - Wortman, Ryan Cristopher
AU - Genders, Shannyn G.
AU - Hale, Matthew W.
AU - O'Shea, Ross
AU - Djouma, Elvan
AU - van den Buuse, Maarten
AU - Church, Jarrod E.
AU - Christie, Brian R.
AU - Drummond, Grant
AU - Sobey, Christopher G
AU - McDonald, Stuart
PY - 2019/7/15
Y1 - 2019/7/15
N2 - Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research.
AB - Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research.
KW - anesthesia
KW - astrocytes
KW - behavior
KW - microglia
KW - mild traumatic brain injury
KW - neuroinflammation
UR - https://www.scopus.com/pages/publications/85068497669
U2 - 10.1089/neu.2018.6169
DO - 10.1089/neu.2018.6169
M3 - Article
C2 - 30843474
AN - SCOPUS:85068497669
SN - 0897-7151
VL - 36
SP - 2260
EP - 2271
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 14
ER -