The evolution of traumatic brain injury in a rat focal contusion model

Abstract

Serial magnetic resonance imaging (MRI) facilitates the in vivo analysis of the intra- and intersubject evolution of traumatic brain injury (TBI) lesions. Despite the availability of MRI, the natural history of experimental focal contusion lesions in the controlled cortical impact (CCI) rat model has not been well described. We performed CCI on rats and MRI during the acute to chronic stages of cerebral injury to investigate the time course of changes in the brain. Female Wistar rats underwent CCI of their left motor cortex with a flat impact tip driven by an electromagnetic piston. In vivo MRI was performed at 7 T serially over six weeks post-CCI. The appearance of CCI-induced lesions and lesion-associated cortical volumes were variable on MRI, with the percent change in cortical volume of the CCI ipsilateral side to the contralateral side ranging from 18% within 2 hours of injury on Day 0 to a peak of 35% on Day 1 and a trough of -28% by Week 5/6, with an average standard deviation of ±14% at any given time point. In contrast, the percent change of ipsilateral side to contralateral side cortical volumes in control rats was not significant (1%±2%). Hemorrhagic conversion within and surrounding the CCI lesion occurred between days 2 and 9 in 45% of rats with no hemorrhage noted on initial scan. Furthermore, hemorrhage and hemosiderin within the lesion were positive for Prussian blue and highly autofluorescent on histological examination. Although some variation in injuries may be technique related, the divergence of similar lesions between initial and final scans demonstrates the inherent biological variability of the CCI rat model.

Imaging of Spontaneous Ventriculomegaly and Vascular Malformations in Wistar Rats: Implications for Preclinical Research

“…When much attention has been given to the generation of disease models, the baseline characteristics of the animals used have typically been assumed to be normal in the absence of external behavioral or physical signs. The inadvertent inclusion of ventriculomegaly Wistar rats in neurological studies may contribute variability to experiments that lead to unforeseen bias in studies of low sample size (53). Beyond the implications that these ventriculomegaly rats may have for interpretation of experimental results, this newly documented form of ventriculomegaly may be importance as an animal model to study hydrocephalus/ventriculomegaly in association with cyst formation and/or vascular malformations.…”

Macrophagic and microglial responses after focal traumatic brain injury in the female rat

“…As previously described [24], a 6-mm craniotomy was followed by CCI with a 5-mm flat impactor tip over the left motor cortex (2.5 mm left lateral and 1.0 mm anterior from the bregma; velocity = 5 m/s, depth = 2.5 mm and dwell time = 100 ms). The same surgeon performed all CCI surgeries for a given cohort of rats.…”

“…Brains were imaged using a 7-T Bruker vertical bore magnet (Bruker BioSpin, Billerica, MA, USA) with a 10-mm inner diameter birdcage coil with a three-dimensional multiecho gradient echo sequence: repetition time (TR) = 200 ms, effective echo time (TE) = 17.5 ms (six echoes, 5 ms echo spacing), field of view = 3.0 × 1.5 × 1.25 cm 3 , 512 × 256 × 128 matrix, four averages and 30° flip angle as previously described [24]. …”

The Revised Neurobehavioral Severity Scale (NSS‐R) for Rodents

“…Additionally, these investigators exposed animals to stress, and reported stress alone did not increase NSS-R scores. Using a CCI model, Turtzo et al (2013) reported significant increases in NSS-R scores at 1 and 14 days post-injury, with scores returning to baseline levels at 28 days post-injury.…”