Cognitive impairment is the most frequent cause of disability in humans following traumatic brain injury (TBI), yet the behavioral tasks used to assess cognitive behavior in rodent models of brain injury are underrepresented in the field. Additionally, few of these tasks have been used to assess behavior across degrees of injury severity. The goal of the present study was to compare four behavioral tasks commonly used in the field in frontally-injured rats with both mild and moderate-to-severe brain injuries. At the start of the study, rats were assigned to two of the following behavioral tasks: Dig scent discrimination (Dig) task, novel object recognition (NOR) task, Morris water maze (MWM), and passive avoidance (PA) task. Four days prior to injury, Dig rats were trained to dig in unscented sand and MWM rats were trained to locate a hidden platform positioned in the northeast quadrant of the MWM. Following training, bilateral controlled cortical impact injuries were induced (mild bilateral frontal TBI, moderate-to-severe bilateral frontal TBI, or non-injured, sham). Following a seven day recovery period, rats were tested on the two assigned behavioral tasks. Following testing, linear mixed effects modeling was performed assessing performance differences on the four tasks as a function of injury (injured vs. non-injured), injury severity (mild TBI vs. moderate-to-severe TBI), and task interaction. The results indicated that, while all four behavioral tasks were effective at assessing injury, some of the tasks were more effective at differentiating between injury severities than others. Specifically, the Dig task and MWM were effective at differentiating between rats with mild TBIs and rats with moderate-to-severe TBIs. Interactions between tasks also occurred such that Dig rats also assigned to the NOR task had significantly higher learning curves on the scent discriminations. The results from the current study indicate that all four behavioral tasks have the potential to assess cognitive impairment after TBI. However, these results are only a beginning. More work is needed before we can fully understand the efficacy of each of these tasks as behavioral assessment measures for cognitive functioning after TBI.

Behavioral evidence suggests that Asian elephants strongly rely on their sense of smell in a variety of contexts including foraging and social communication. Using a food-rewarded two-alternative operant conditioning procedure, three female Asian elephants were tested on their olfactory discrimination ability with 1-aliphatic alcohols, n-aldehydes, 2-ketones, n-carboxylic acids and with a set of twelve enantiomeric odor pairs. When presented with pairs of structurally related aliphatic odorants, the discrimination performance of the elephants increased with decreasing structural similarity of the odorants. Nevertheless, the animals successfully discriminated between all aliphatic odorants even when these only differed by one carbon atom. The elephants were also able to discriminate between all twelve enantiomeric odor pairs tested. Additionally, the elephants showed an excellent long-term odor memory and remembered the reward value of previously learned odor pairs after three weeks and one year of recess. Compared to other species tested previously on the same sets of odorants, the Asian elephants performed at least as good as mice and clearly better than human subjects, South African fur seals, squirrel monkeys, pigtail macaques, and honeybees. Taken together, these results support the notion that the sense of smell may play an important role in regulating the behavior of Asian elephants.

Frontotemporal lobar degeneration (FTLD) is an early onset neurodegenerative disorder which selectively destroys frontal and temporal cortical neurones. The resulting damage leads to a range of language and behavioural deficits, however, episodic memory is generally maintained. Around 10% of FTLD cases are caused by progranulin gene mutations that lead to haploinsufficiency and reduced expression of progranulin. Secretory leukocyte protease inhibitor (SLPI) has been shown to have a key protective effect over progranulin, inhibiting enzymatic cleavage by neutrophil elastase. Previous work demonstrating this role of SLPI is largely from in vitro studies and scenarios with above-physiological SLPI concentrations. To ascertain a role for endogenous SLPI in the regulation of progranulin a murine SLPI knockout model was used and tonic progranulin measurements taken. No change in circulating progranulin levels were seen in SLPI null mice (at 6, 12 or 20 months of age) when compared to non-transgenic controls, though significant differences were observed between male and female SLPI null animals. Similarly, tissue (brain and lung) levels of progranulin were comparable between wild-type and SLPI null mice, despite the presence of active neutrophil elastase. Behavioural analysis of SLPI null mice revealed no major phenotype when compared to wild-type, over a range of behavioural tests. However primary neuronal cultures taken from SLPI null mice did display an elevated progranulin response to bacterial lipopolysaccharide (LPS). These data suggest that, although SLPI may play a role in progranulin regulation during an inflammatory event, it is unlikely to play a major role in progranulin regulation under basal conditions, as reported previously. Therefore under disease conditions regulation of extracellular progranulin is likely through other modulatory factors that have yet to be described.

<p>The aim of the present study was to determine the distributions of and correlations between hand preference, visual acuity and eye preference through a series of tests in 50 males 50 females aged between 17 and 39 years. Handedness was determined through the Edinburgh handedness inventory questionnaire. The handedness distribution was: right-handed 90%, left-handed 1 %, and ambidextrous 9%. I found that 30 % had better visual acuity with their right eye, 39 % had better visual acuity with their left eye, and 31% had the same visual acuity with both eyes. 75.2% on average used their right eye in the battery of tests and 24.8% on average used their left eye. There were no statistically significant differences between the sexes or age groups with any of the measures. No correlation was found between eye preference and visual acuity or eye preference and hand preference among all subjects. No statistically significance between the sexes was found.</p>

The aim of the present study was to determine the distributions of and correlations between hand preference, visual acuity and eye preference through a series of tests in 50 males 50 females aged between 17 and 39 years. Handedness was determined through the Edinburgh handedness inventory questionnaire. The handedness distribution was: right-handed 90%, left-handed 1 %, and ambidextrous 9%. I found that 30 % had better visual acuity with their right eye, 39 % had better visual acuity with their left eye, and 31% had the same visual acuity with both eyes. 75.2% on average used their right eye in the battery of tests and 24.8% on average used their left eye. There were no statistically significant differences between the sexes or age groups with any of the measures. No correlation was found between eye preference and visual acuity or eye preference and hand preference among all subjects. No statistically significance between the sexes was found.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

A spinal cord injury (SCI) is a damage to the spinal cord that causes permanent or temporary changes in motor and sensory functions. In humans, the traumatic impact to spinal cord is mostly directed from the ventral part of the spinal column, even though SCI models are principally directed from the dorsal part of the spinal column due to easier surgery. The aim of the work described in this thesis was to develop clinically more relevant, easily reproducible and relatively inexpensive model of the ventral spinal cord lesion in rats which replicates SCI in humans as closely as possible by its pathology, completeness, level and regeneration. For the surgery we used a modification of a balloon- compression technique. The balloon of the 2F embolectomy Fogarty's catheter was placed to the anterior epidural space via laminectomy at the level of T10 and when the final position of the catheter was achieved at the spinal level T8 in front of the anterior median fissure, a balloon was rapidly inflated with 10 μl or 15 μl of water for 5 minutes. Other two groups - laminectomy only and ventral placement of the catheter without inflation were used as controls. The motor functions were evaluated by the BBB test and ladder walking test. In BBB test we observed significantly impaired motor functions in the 15 μl...

There is little knowledge about olfactory learning in primates, even though primates are known to use olfaction in several behaviors including food selection and territorial defense. Therefore I assessed the olfactory learning and memory performance in five adult spider monkeys (Ateles geoffroyi) using a food-rewarded two-choice olfactory discrimination paradigm. The spider monkeys acquired the initial odor discrimination in 530-1102 trials and in a series of intramodal transfer tasks they needed 30-510 trials to reach the learning criterion. There was a significant negative correlation between the number of trials needed to reach the learning criterion and the number of transfer tasks completed. Thus, as a group, the animals displayed olfactory learning set formation. The number of trials that the spider monkeys needed in initial olfactory learning was comparable to that of other primate species tested previously but higher compared to that of other mammals such as dogs and rats. The learning speed of the spider monkeys in intramodal transfer tasks was similar to that of other mammals tested, suggesting that primates are less prepared to use olfactory cues in the initial solving of a problem but that once they learn the concept, their learning speed with novel odor discrimination problems is not generally slower than that of non-primate mammals. All spider monkeys tested reached the learning criterion in the memory tasks straight on the first testing day, that is: within 30 trials, suggesting similar long-term odor memory capabilities in spider monkeys and other mammals such as dogs, mice and rats.

The sense of smell plays an important role in regulating the behavior of Asian elephants but until now, no behavioral test to systematically assess the olfactory capabilities of this species existed. Using a voluntary, food-rewarded two-alternative operant conditioning procedure, three female Asian elephants were successfully taught to discriminate between rewarded and unrewarded odors and also succeeded in intramodal stimulus transfer tasks in which either the rewarded odor, or the unrewarded odor, or both odors were exchanged simultaneously for new odors. The animals readily mastered the initial task within only 120 stimulus contacts, demonstrating rapid olfactory learning and performing at least as good as rodents and dogs and even better than other species, including nonhuman primates, tested in similar studies before. When presented with pairs of structurally related odorants, the discrimination performance of the elephants decreased with increasing structural similarity of the odorants, but the animals still significantly discriminated between aliphatic acetic esters even when they only differed by one carbon chain length. The elephants also demonstrated an excellent long-term odor memory and successfully remembered the reward value of previously learned odor stimuli after two, four, eight and even 16 weeks of recess in testing. The paradigm developed and applied in the present study proved to be useful to assess the olfactory capabilities in Asian elephants.