Developing a Clinically Relevant Model of Cognitive Training After Experimental Traumatic Brain Injury (original) (raw)
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Restorative neurology and neuroscience, 2006
As deficits in memory and cognition are commonly observed in survivors of traumatic brain injury (TBI), causing reduced quality of life for the patient, a major goal in experimental TBI research is to identify and evaluate cognitive dysfunction. The present study assessed the applicability of the serial Morris water maze (MWM) test to determine cognitive function following experimental TBI in the same group of rats which is particularly important for long-term studies and increasingly valuable for the evaluation of novel treatment strategies. Male Sprague-Dawley rats (n = 27) were anesthetized and subjected to either sham injury (n = 9) or lateral fluid percussion (FP) brain injury of moderate severity (n = 18). At 4 weeks post-injury, animals were trained in a water maze over 3 days (acquisition/learning phase) to find a submerged platform. At 8 weeks post-injury the hidden platform was then moved to the opposite quadrant, and animals were trained to find the new position of the pl...
Physiological research / Academia Scientiarum Bohemoslovaca, 2011
The aim of the present study was to quantify the effect of multisensory rehabilitation on rats' cognition after an experimental brain trauma and to assess its possible clinical implications. The complex intermittent multisensory rehabilitation consisted of currently used major therapeutic procedures targeted at the improvement of cognitive functions; including multisensory and motor stimulation and enriched environment. We have confirmed this positive effect of early multisensory rehabilitation on the recovery of motor functions after traumatic brain injury. However, we have been able to prove a positive effect on the recovery of cognitive functions only with respect to the frequency of efficient search strategies in a Barnes maze test, while results for search time and travelled distance were not significantly different between study groups. We have concluded that the positive effects of an early treatment of functional deficits are comparable with the clinical results in early...
Neurorehabilitation and neural repair, 2015
Previous work demonstrates that spatial (explicit) and nonspatial (implicit) elements of place learning in the Morris water maze (MWM) task can be dissociated and examined in the context of experimental traumatic brain injury (TBI). Providing nonspatial cognitive training (CT) after injury can improve place learning compared with untrained controls. In the present study, we hypothesized that brief exposure to extra-maze cues, in conjunction with CT, may further improve MWM performance and extra-maze cue utilization compared with CT alone. Adult male Sprague-Dawley rats (n = 66) received controlled cortical impact (CCI) injury or sham surgery. Beginning day 8 postsurgery, CCI and sham rats received 6 days of no training (NT) or CT with/without brief, noncontextualized exposure to extra-maze cues (BE and CT, respectively). Acquisition (days 14-18), visible platform (VP; day 19), carryover (CO; days 20-26), and periodic probe trials were performed. Platform latencies, peripheral and ta...
2020
Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not receive training performed poorer compared to m...
PLOS ONE, 2020
Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not receive training performed poorer compared to mice trained. To further validate our RAWM protocol, we used scopolamine. We, also, demonstrated that a single mild closed head injury (CHI) caused deficits in this task at two weeks post-CHI. Our data supported the use of 7 trials per day and a spaced training protocol as key factor to unmask memory impairment following CHI. Here, we provide a detailed standard operating procedure for RAWM test, which can be applied to a variety of mouse models including neurodegenerative diseases and pathology, as well as when pharmacological approaches are used.
Selective cognitive impairment following traumatic brain injury in rats
Behavioural Brain Research, 1993
Impairment of cognitive abilities is a frequent and significant sequelae of traumatic brain injury (TB1). The purpose of this experiment was to examine the generality of the cognitive deficits observed after TBI. The performance of three tasks was evaluated. Two of the tasks (passive avoidance and a constant-start version of the Morris water maze) were chosen because they do not depend on hippocampal processing. The third task examined was the standard version of the Morris water maze which is known to rely on hippocampal processing. Rats were either injured at a moderate level (2.1 atm) of fluid percussion brain injury or surgically prepared but not injured (sham-injured control group). Nine days after fluid percussion injury, injured (n = 9) and sham-injured rats (n = 8) were trained on the one-trial passive avoidance task with retention assessed 24 h later. On days 11-15 following injury, injured (n -9) and sham-injured (n -8) rats were trained on a constant-start version of the Morris water maze that has the animals begin the maze from a fixed start position on each trial. Additional injured (n -8) and shaminjured (n-8) animals were trained on days 11-15 after injury on the standard (i.e. using variable start positions) version of the Morris water maze. The results of this experiment revealed that performance of the passive avoidance and the constant-start version of the Morris water maze were not impaired by fluid percussion TBI. However, performance on a task that is usually disrupted by hippocampal damage (variable-start version of the Morris water maze) was significantly impaired by TBI. Thus, the hippocampus appears to be selectively damaged following TBI.
Working Memory Deficits following Traumatic Brain Injury in the Rat
2009
This study was designed to examine working memory following fluid-percussion traumatic brain injury (TBI) using the Morris water maze (MWM). Rats were injured (« = 9) at a moderate level of central fluid percussion injury (2.1 atm) or were prepared for injury but did not receive a fluid pulse (sham injury) (n = 10). On days 11-15 postinjury, working memory was assessed using the MWM. Each animal received 8 pairs of trials per day. For each pair of trials, animals were randomly assigned to one of four possible starting points and one of four possible escape platform positions. On the first trial of each pair, rats were placed in the maze facing the wall and were given 120 sec to locate the hidden escape platform. After remaining on the goal platform for 10 sec, they were placed back into the maze for the second trial of the pair. The platform position and the start position remained unchanged on this trial. After the second trial, the animal was given a 4 min intertrial rest. Between pairs of trials, both the start position and the goal location were changed. Analyses of the latency to reach the goal platform indicated that sham-injured animals performed significantly better on the second trial than on the first trial of each pair. However, injured animals did not significantly differ between first and second trial goal latencies on any day. These results indicate that injured animals have a profound and enduring deficit in spatial working memory function on days 11-15 after TBI.
Closed-head minimal traumatic brain injury produces long-term cognitive deficits in mice
Neuroscience, 2003
Victims of minimal traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study we adopted a non-invasive closed-head weight-drop mouse model to produce mTBI. We examined the effects of 20, 25, or 30 g weight drop 7, 30, 60 and 90 days following injury on mice's ability to perform the Morris water maze. The mice suffered profound long-lasting learning and memory deficits that were force-and time-dependent. Although the injured mice could acquire the task, they could not improve their initial escape latency by more than 50%, while normal mice improved by up to 450% (P<0.001). In order to directly compare the learning ability of individual mice following our mTBI we have devised a new measure which we term learning rate. We define learning rate as the rate the mouse improved its own performance in consecutive trials in a given experimental day. The learning rate of control mice increased linearly throughout the testing period with a slope of approximately 0.9. Injured mice that sustained 20 and 25 g weight drop could also improve their learning rate linearly but with a slope of only 0.2. Mice who sustained 30 g weight drop could not improve their learning rate linearly and reached a plateau after the third experimental learning day. These results indicate that the severity of injury may correlate with the degree of integration of the learning task. These cognitive deficits occurred without any other clear neurological damage, no evident brain edema, no notable damage to the blood-brain barrier and no early anatomical changes to the brain (observed by magnetic resonance imaging imaging). These results demonstrate that persistent deficits of cognitive learning abilities in mice, similar to those observed in human post-concussive syndrome, can follow mTBI without any anatomical damage to the brain and its surrounding tissue. (C. G. Pick). Abbreviations: ANOVA, analysis of variance; BBB, blood-brain barrier; MRI, magnetic resonance imaging; mTBI, minimal traumatic brain injury; MWM, Morris water maze; TBI, traumatic brain injury.