Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury
Authors: Hui Zhang
Derek Lindsey
Tony Wyss-Coray
Saul Villeda
Gregor Bieri
Zhaoqing Ding
Gary S Beaupre
Joseph M Castellano
Andy Nguyen
Jian Luo
Journal: Frontiers in Neurology (2014)
Discipline: CLINICAL MEDICINE
Keywords: astrogliosis; bioluminescence; long-term; mild traumatic brain injury; neurobehavior.
Affiliations: Department of Neurology and Neurological Sciences, Stanford University School of Medicine , Stanford, CA , USA ; Center for Tissue Regeneration, Repair and Restoration, VA Palo Alto Health Care System , Palo Alto, CA , USA., Center for Tissue Regeneration, Repair and Restoration, VA Palo Alto Health Care System , Palo Alto, CA , USA.

Abstract:  Mild traumatic brain injury (mTBI, also referred to as concussion) accounts for the majority of all traumatic brain injuries. The consequences of repetitive mTBI have become of particular concern for individuals engaged in certain sports or in military operations. Many mTBI patients suffer long-lasting neurobehavioral impairments. In order to expedite pre-clinical research and therapy development, there is a need for animal models that reflect the long-term cognitive and pathological features seen in patients. In the present study, we developed and characterized a mouse model of repetitive mTBI, induced onto the closed head over the left frontal hemisphere with an electromagnetic stereotaxic impact device. Using GFAP-luciferase bioluminescence reporter mice that provide a readout of astrocyte activation, we observed an increase in bioluminescence relative to the force delivered by the impactor after single impact and cumulative effects of repetitive mTBI. Using the injury parameters established in the reporter mice, we induced a repetitive mTBI in wild-type C57BL/6J mice and characterized the long-term outcome. Animals received repetitive mTBI showed a significant impairment in spatial learning and memory when tested at 2 and 6 months after injury. A robust astrogliosis and increased p-Tau immunoreactivity were observed upon post-mortem pathological examinations. These findings are consistent with the deficits and pathology associated with mTBI in humans and support the use of this model to evaluate potential therapeutic approaches. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 Not even close as a duplicate , 
 #2 I think ImageTwin has correctly identified a problem with Fig 8. ![file] , 
 Dear Hoya Camphorifolia, Thank you very much for your comments. We will investigate and look at the original image files to verify if there is an error in this figure. We will keep you updated with our progress and findings. Best wishes, Jian , 
 #3 Clearly. The previous commenter may not have caught the difference in orientation. Similar issues in these papers with common authors: https: pubpeer.com publications D770310C83B6E77C7D2225BDFF1CCC https: pubpeer.com publications 9CC94A1B7AE40D4D5B819FF4AD01EA https: pubpeer.com publications 9E5205AE105EB03B8AFA346C0EEADF Common first author: https: pubpeer.com publications C1F2BF3AB0277B837CFC5862487A35 , 
 Dear Hoya and Actinopolyspora, We checked carefully and found that the highlighted left side of Figure 8 was a mistake introduced during figure making. This part of the Figure was intended to show little p-Tau immunoreactivity in the CA3 of sham animals. While this mistake does not affect the conclusion of the paper, we sincerely apologize for it. We are working with the editorial office to correct it. Thank you also for identifying potential mistakes in other papers. We will check each of them and respond accordingly. To avoid similar mistakes in the future, we revised our workflow of figure making and added additional steps of quality check. Thank you again for your efforts. Jian ,