Richelle Mychasiuk1, Harleen Hehar2, Sydeny Candy2, Irene Ma2, Michael J Esser2. 1. Alberta Children's Hospital Research Institute, University of Calgary, Faculty of Medicine, Heritage Medical Research Building Room 274, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 1N4. Electronic address: rmmychas@ucalgary.ca. 2. Alberta Children's Hospital Research Institute, University of Calgary, Faculty of Medicine, Heritage Medical Research Building Room 274, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 1N4.
Abstract
BACKGROUND: The translation of research to clinical application is only as good as the modelling platforms employed. This study sought to improve understanding of mild traumatic brain injury (mTBI), by examining the importance of acceleration and rotational force directions on behavioural and molecular outcomes. It is believed that many symptoms associated with concussive forms of mTBI are related to white matter and fibre tract damage. Given that rodents have significantly less white matter, could changes in acceleration/rotational force directionality alter outcomes? NEW METHOD/COMPARISON WITH EXISTING METHODS: Comparison of mTBIs with two distinct injury platforms, the lateral impact (LI) device, which produces horizontal acceleration/rotation; or the modified weight drop (WD) device, which produces sagittal or vertical acceleration/rotation. Male and female rats underwent a behavioural test battery followed by analysis of 5 TBI-associated biomarkers (BDNF, Eno2, GFAP, MAPT, TERT) from the prefrontal cortex and hippocampus. RESULTS: Acute behavioural impairments were similar for both injury models; animals exhibited increased time-to-wake, and deficits of balance and motor control. However, as the post-injury interval increased LI animals displayed deficits on tasks related to emotional functioning, whereas WD animals showed impairment in cognitive measures. Biomarker expression varied as a function of injury platform, sex, and brain region. CONCLUSION: Just as with humans, the direction of the acceleration and rotational forces produced injuries in different networks and connections, resulting in altered functional deficits for rodents as well. These findings suggest that rodents are a valuable resource for the study of mTBI, when appropriately modelled.
BACKGROUND: The translation of research to clinical application is only as good as the modelling platforms employed. This study sought to improve understanding of mild traumatic brain injury (mTBI), by examining the importance of acceleration and rotational force directions on behavioural and molecular outcomes. It is believed that many symptoms associated with concussive forms of mTBI are related to white matter and fibre tract damage. Given that rodents have significantly less white matter, could changes in acceleration/rotational force directionality alter outcomes? NEW METHOD/COMPARISON WITH EXISTING METHODS: Comparison of mTBIs with two distinct injury platforms, the lateral impact (LI) device, which produces horizontal acceleration/rotation; or the modified weight drop (WD) device, which produces sagittal or vertical acceleration/rotation. Male and female rats underwent a behavioural test battery followed by analysis of 5 TBI-associated biomarkers (BDNF, Eno2, GFAP, MAPT, TERT) from the prefrontal cortex and hippocampus. RESULTS: Acute behavioural impairments were similar for both injury models; animals exhibited increased time-to-wake, and deficits of balance and motor control. However, as the post-injury interval increased LI animals displayed deficits on tasks related to emotional functioning, whereas WD animals showed impairment in cognitive measures. Biomarker expression varied as a function of injury platform, sex, and brain region. CONCLUSION: Just as with humans, the direction of the acceleration and rotational forces produced injuries in different networks and connections, resulting in altered functional deficits for rodents as well. These findings suggest that rodents are a valuable resource for the study of mTBI, when appropriately modelled.
Authors: Teodor T Postolache; Abhishek Wadhawan; Adem Can; Christopher A Lowry; Margaret Woodbury; Hina Makkar; Andrew J Hoisington; Alison J Scott; Eileen Potocki; Michael E Benros; John W Stiller Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472
Authors: Jahnavi Mundluru; Abdul Subhan; Tsz Wai Bentley Lo; Nathan Churchill; Luis Fornazzari; David G Munoz; Tom A Schweizer; Corinne E Fischer Journal: J Neurotrauma Date: 2020-10-20 Impact factor: 5.269