Changes in F-18-fluorodeoxyglucose ([F-18]FDG) measured by positron emission tomography (PET) can be used for the noninvasive detection of metabolic dysfunction following mild traumatic brain injury (mTBI). This study examined the time course of metabolic changes induced by primary blast injury by measuring regional [F-18]FDG uptake. Adult, male rats were exposed to blast overpressure (15 psi) or sham injury, and [F-18]FDG uptake was measured before injury and again at 1-3 h and 7 days post-injury, using both volume-of-interest (VOI) and voxel-based analysis. VOI analysis revealed significantly increased [F-18]FDG uptake in corpus callosum and amygdala at both 1-3 h and 7 days following blast, while a transient decrease in uptake was observed in the midbrain at 1-3 h only. Voxel-based analysis revealed similar significant differences in uptake between sham and blast-injured rats at both time points. At 1-3 h post-injury, clusters of increased uptake were found in the amygdala, somatosensory cortex, and corpus callosum, while regions of decreased uptake were observed in midbrain structures (inferior colliculus, ventrolateral tegmental area) and dorsal auditory cortex. At day 7, a region of increased uptake in blast-injured rats was found in a cluster centered on the cortex-amygdala transition zone, while no regions of decreased uptake were observed. These results suggest that a relatively mild primary blast injury results in altered brain metabolism in multiple brain regions and that post-injury time of assessment is an important factor in observing regional changes in [F-18]FDG uptake.

Animal models play a critical role in understanding the biomechanical, pathophysiological, and behavioral consequences of traumatic brain injury (TBI). In preclinical studies, cognitive impairment induced by TBI is often assessed using the Morris water maze (MWM). Frequently described as a hippocampally dependent spatial navigation task, the MWM is a highly integrative behavioral task that requires intact functioning in numerous brain regions and involves an interdependent set of mnemonic and non-mnemonic processes. In this chapter, we review the special considerations involved in using the MWM in animal models of TBI, with an emphasis on maximizing the degree of information extracted from performance data. We include a theoretical framework for examining deficits in discrete stages of cognitive function and offer suggestions for how to make inferences regarding the specific nature of TBI-induced cognitive impairment. The ultimate goal is more precise modeling of the animal equivalents of the cognitive deficits seen in human TBI.

Memory impairment is common following traumatic brain injury. However, the specific processes underlying the impairments remain unknown. Traumatic brain injury may interfere with several of the stages of the learning and memory process. In two separate experiments, we examined the specific nature of both anterograde and retrograde memory dysfunction following fluid percussion brain injury in rats. In Experiment 1, we examined the retention of spatial memory in the MWM after equating initial learning between sham and injured animals. Animals were trained to criterion and then tested for retention 4, 8, or 24 h post-training. Although injured animals displayed deficits in task acquisition, retention performance was not significantly different between groups. In Experiment 2, we examined the effects of injury on the retention of retrograde spatial memories in the MWM. Animals were injured either 1 or 14 days post-training and then received retention probe trials followed by a reminding procedure and second probe trial 14 days post-injury. All injured animals displayed retention deficits in the probe trials 14 days post-injury. However, after the reminding procedure, injured animals displayed sham-level performance during the second probe trial. The results of these experiments suggest that with anterograde memory impairment induced by traumatic brain injury, the primary deficit lies in task acquisition, not the retention of information within long-term memory. Retrograde memory impairment following injury appears to be mediated primarily by deficits in memory retrieval.

Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. Three experiments were performed to determine (1) the optimal dose of aniracetam for treating cognitive impairment, (2) the effect of delaying drug treatment for a period of days following TBI, and (3) the effect of terminating drug treatment before cognitive assessment. In experiment 1, rats were administered moderate fluid percussion injury and treated with vehicle, 25, or 50 mg/kg aniracetam for 15 days. Both doses of aniracetam effectively reduced injury-induced deficits in the Morris water maze (MWM) as measured on postinjury days 11-15. In experiment 2, injured rats were treated with 50 mg/kg aniracetam or vehicle beginning on day 11 postinjury and continuing for 15 days. MWM performance, assessed on days 26-30, indicates that aniracetam-treated animals performed as well as sham-injured controls. In experiment 3, animals were injured and treated with aniracetam for 15 days. Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.

Chronic cognitive impairment is a frequent and enduring aspect of traumatic brain injury in both humans and animals. Animal models of traumatically induced cognitive impairment provide the groundwork for future clinical studies aimed at treating chronic cognitive dysfunction after head injury. This article will review the results of posttraumatic neurotransmitter-based interventions aimed at improving cognitive recovery in animal models of traumatic brain injury. The scope of this review is limited to experiments designed to treat the chronic stages of head injury, and the interventions tested must have been initiated after injury and continued for a period of days. Where applicable, results from clinical studies are considered. A brief review of current techniques used in experimental traumatic brain injury are presented.