Long-term increase in sensitivity to ketamine's behavioral effects in mice exposed to mild blast induced traumatic brain injury.

Neurobehavioral deficits emerge in nearly 50% of patients following a mild traumatic brain injury (TBI) and may persist for months. Ketamine is used frequently as an anesthetic/analgesic and for management of persistent psychiatric complications. Although ketamine may produce beneficial effects in patients with a history of TBI, differential sensitivity to its impairing effects could make the therapeutic use of ketamine in TBI patients unsafe. This series of studies examined male C57BL/6 J mice exposed to a mild single blast overpressure (mbTBI) for indications of altered sensitivity to ketamine at varying times after injury. Dystaxia (altered gait), diminished sensorimotor gating (reduced prepulse inhibition) and impaired working memory (step-down inhibitory avoidance) were examined in mbTBI and sham animals 15 min following intraperitoneal injections of saline or R,S-ketamine hydrochloride, from day 7-16 post injury and again from day 35-43 post injury. Behavioral performance in the forced swim test and sucrose preference test were evaluated on day 28 and day 74 post injury respectively, 24 h following drug administration. Dynamic gait stability was compromised in mbTBI mice on day 7 and 35 post injury and further exacerbated following ketamine administration. On day 14 and 42 post injury, prepulse inhibition was robustly decreased by mbTBI, which ketamine further reduced. Ketamine-associated memory impairment was apparent selectively in mbTBI animals 1 h, 24 h and day 28 post shock (tested on day 15/16/43 post injury). Ketamine selectively reduced immobility scores in the FST in mbTBI animals (day 28) and reversed mbTBI induced decreases in sucrose consumption (Day 74). These results demonstrate increased sensitivity to ketamine in mice when tested for extended periods after TBI. The results suggest that ketamine may be effective for treating neuropsychiatric complications that emerge after TBI but urge caution when used in clinical practice for enhanced sensitivity to its side effects in this patient population.

Are changes in behavior of fast-growing broilers with slight gait impairment (GS0-2) related to pain?

Impaired walking ability in terms of slight or definite defects is more common in broiler production than lameness that obviously hinders movement, but it has received limited scientific attention. This study aimed to compare behavior of conventional broilers with impaired walking ability (assessed as gait score (GS) 2) with those walking normally (GS0) and those with only a slight gait defect (GS1). Behavior in the home environment was registered, and an analgesic intervention to quantify changes in time budgets indicating pain relief was applied. The study included 192 Ross 308 broilers. On day 27 of age, the birds were distributed as evenly as possible into birds of GS0 and GS2 of each sex based on obtained gait score. Following this, each experimental bird was housed with 3 companion birds. On days 30 and 32 of age, the behavior in the home pens was recorded. All experimental birds were injected with the NSAID carprofen on one of the 2 d and saline on the other. The statistical analyses used the GS scored on the day of recording as explanatory factor. Compared to GS0 birds, GS2 birds tended to be more inactive (mean (CI): 4,193 (3,971-4416) vs. 4,005 (3,753-4,257) s; P = 0.074), spent more time sitting while feeding (306 (266-353) vs. 213 (180-251) s; P = 0.026), were less likely to perch (probability: 0.78 (0.69-0.85) vs. 0.91 (0.85-0.95); P = 0.012), and spent less time performing comfort behavior (749 (689-814) s vs. 875 (792-967) s; P = 0.043). Compared to GS1 birds, GS2 birds spent more time inactive (GS1: 4,022 (3,818-4225) s; P = 0.027), less time foraging (289 (253-329) vs. 347 (309-388) s; P = 0.047), and were less likely to perch (GS1: 0.90 (0.86-0.93); P = 0.001). For some of these behavioral variables, administration of carprofen led to behavioral changes across the GSs, which may suggest that the behavioral expression of the broilers was limited by pain. These findings are of relevance to animal welfare, but the underlying causes are still not fully clarified.

Understanding dairy farmer intentions to make improvements to their management practices of foot lesions causing lameness in dairy cows.

Foot lesions causing lameness in dairy cows have been demonstrated to adversely affect milk yield, reproductive performance and longevity, resulting in significant economic burden to individual dairy farmers and the dairy industry. Further, foot lesions compromise dairy cow welfare. Despite this knowledge, foot lesions remain a large problem in many dairy herds woldwide. Therefore, there is potential for dairy farmers to make changes to their current management practices of foot lesions. This study used the social-psychology framework, the Theory of Planned Behavior (TPB), to explore dairy farmers' intentions to make improvements to their current management practices of foot lesions in their dairy cows and to identify the underlying behavioral, normative and control beliefs facilitating and constraining this behavior. In accordance with the theoretical framework, Australian dairy farmers were invited to participate in an online questionnaire which included questions regarding intentions, attitudes, subjective norms and perceived behavioral control. Fifty-six dairy farmers completed the questionnaire. The overall intention of these dairy farmers to make improvements to their management practices of foot lesions in the next year was moderate. Dairy farmers believed improving their current management practices of foot lesions would improve animal welfare, increase milk production and was worth the cost involved (behavioral beliefs). They indicated that the opinions of consumers, staff, and animal welfare groups were important in their decision to make improvements (normative beliefs). Better equipment and facilities, improved knowledge and training, and a favorable cost-benefit ratio were perceived as factors that would enable dairy farmers to improve their management practices (control beliefs). While all of these beliefs may be considered as potential drivers to facilitate dairy farmers to change their management practices, the behavioral beliefs were identified as the priority beliefs that industry should target in the development of strategies to increase dairy farmer intentions to make improvements to their management practices of foot lesions.

A comparison of the efficacy of three intervention trial types: postal, group, and one-to-one facilitation, prior management and the impact of message framing and repeat messages on the flock prevalence of lameness in sheep.

The aim of this study was to evaluate the effectiveness of three knowledge-transfer intervention trial types (postal, group, one-to-one) to promote best practice to treat sheep with footrot. Further aims were to investigate whether farmer behaviour (i.e. management of lameness) before the trial was associated with uptake of best practice and whether the benefits of best practice framed positively or negatively influenced change in behaviour. The intervention was a message developed from evidence and expert opinion. It was entitled "Six steps to sound sheep" and promoted (1) catch sheep within three days of becoming lame, (2) inspect feet without foot trimming, (3) correctly diagnose the cause, (4) treat sheep lame with footrot or interdigital dermatitis with antibiotic injection and spray without foot trimming, (5) record the identity of treated sheep, (6) cull repeatedly lame sheep. In 2013, 4000 randomly-selected English sheep farmers were sent a questionnaire, those who responded were recruited to the postal (1081 farmers) or one-to-one intervention (32 farmers) trials. A random sample of 400 farmers were invited to join the group trial; 78 farmers participated. A follow-up questionnaire was sent to all participants in summer 2014. There were 72%, 65% and 91% useable responses for the postal, group and one-to-one trials respectively. In both 2013 and 2014, the prevalence of lameness was lower in flocks managed by LC1 farmers than LC2 and LC3 farmers. Between 2013 and 2014, the reduction in geometric mean (95% CI) period prevalence of lameness, proportional between flock reduction in lameness and within flock reduction in lameness was greatest in the one-to-one (7.6% (7.1-8.2%) to 4.3% (3.6-5.0%), 35%, 72%) followed by the group (4.5% (3.9-5.0%) to 3.1% (2.4-3.7%), 27%, 55%) and then the postal trial (from 3.5% (3.3-3.7%) to 3.2% (3.1-3.4%), 21%, 43%). There was a marginally greater reduction in lameness in farmers using most of Six steps but slow to treat lame sheep pre-trial than those not using Six steps at all. There was no significant effect of message framing. The greatest behavioural change was a reduction in therapeutic and routine foot trimming and the greatest attitude change was an increase in negative attitudes towards foot trimming. We conclude that all three intervention trial approaches were effective to promote best practice to treat sheep with footrot with one-to-one facilitation more effective than group and postal intervention trials. Results suggest that farmers' behaviour change was greater among those practising aspects of the intervention message before the trial began than those not practising any aspect.

Producer estimates of prevalence and perceived importance of lameness in dairy herds with tiestalls, freestalls, and automated milking systems.

Lameness is one of the most important welfare and productivity concerns in the dairy industry. Our objectives were to obtain producers' estimates of its prevalence and their perceptions of lameness, and to investigate how producers monitor lameness in tiestall (TS), freestall with milking parlor (FS), and automated milking system (AMS) herds. Forty focal cows per farm in 237 Canadian dairy herds were scored for lameness by trained researchers. On the same day, the producers completed a questionnaire. Mean herd-level prevalence of lameness estimated by producers was 9.0% (±0.9%; ±SE), whereas the researchers observed a mean prevalence of 22.2% (±0.9%). Correlation between producer- and researcher-estimated lameness prevalence was low (r = 0.19) and mean researcher prevalence was 1.6, 1.8, and 4.1 times higher in AMS, FS, and TS farms, respectively. A total of 48% of producers thought lameness was a moderate or major problem in their herds (TS = 34%; AMS =53%; FS = 59%). One third of producers considered lameness the highest ranked health problem they were trying to control, whereas two-thirds of producers (TS = 43%; AMS = 63%; FS = 71%) stated that they had made management changes to deal with lameness in the past 2 yr. Almost all producers (98%) stated they routinely check cows to identify new cases of lameness; however, 40% of producers did not keep records of lameness (AMS = 24%; FS = 23%; TS = 60%). A majority (69%) of producers treated lame cows themselves immediately after detection, whereas 13% relied on hoof-trimmer or veterinarians to plan treatment. Producers are aware of lameness as an issue in dairy herds and almost all monitor lameness as part of their daily routine. However, producers underestimate lameness prevalence, which highlights that lameness detection continues to be difficult in in all housing systems, especially in TS herds. Training to improve detection, record keeping, identification of farm-specific risk factors, and treatment planning for lame cows is likely to help decrease lameness prevalence.

Cow-level associations of lameness, behavior, and milk yield of cows milked in automated systems.

This study evaluated differences in behavior and productivity between lame and nonlame cows in herds with automated milking systems (AMS). We monitored 30 cows per herd on 41 farms with AMS in Canada (26 herds in Ontario and 15 herds in Alberta). During a 6-d period, milking data (n = 1,184) and lying behavior data (n = 1,209) were collected from cows on 41 farms. Rumination behavior (n = 569) and activity (n = 615) data were available for cows at 22 farms. Locomotion was scored using a numerical rating system (NRS; 1 = sound; 5 = extremely lame). Cows were defined as clinically lame with NRS ≥ 3 (n = 353, 29%) and nonlame with NRS < 3 (n = 865, 71%). Greater parity, lower body condition, and lower environmental temperature were factors associated with lameness. When accounting for other factors, lame cows produced 1.6 kg/d less milk in 0.3 fewer milkings/d. Lame cows were 2.2 times more likely to be fetched more than 1 time during the 6-d period and spent 38 min/d more time lying down in bouts that were 3.5 min longer in comparison with nonlame cows. As the number of cows per AMS unit increased, the frequency of milkings and refusals per cow per day decreased and cow activity increased. For each 13.3-percentage-point increase in freestall stocking density (cows per stall), daily lying time decreased by 13 min/d and cows were 1.6 times more likely to be fetched more than 1 time during the 6-d period. There was no difference in daily rumination or activity between lame and nonlame cows or in night:day rumination time, but lame cows had greater night:day activity ratios. This study supports the growing knowledge that lameness has negative effects on milk production, voluntary milking behavior, and lying behavior of cows in herds with AMS. These results may help dairy producers gain a better appreciation of the negative effects of even moderate cases of lameness and may help motivate them to improve their lameness monitoring and treatment protocols.

Associations between sheep farmer attitudes, beliefs, emotions and personality, and their barriers to uptake of best practice: The example of footrot.

There is interest in understanding how farmers' behaviour influences their management of livestock. We extend the theory of planned behaviour with farmers attitudes, beliefs, emotions and personality to investigate how these are associated with management of livestock disease using the example of footrot (FR) in sheep. In May 2013 a one-year retrospective questionnaire was sent to 4000 sheep farmers in England, requesting data on lameness prevalence, management of footrot, farm/flock descriptors, and farmer-orientated themes: barriers to treating footrot, opinions and knowledge of footrot, relating to other people and personality. Principal component analysis (PCA) was used to make composite variables from explanatory variables and latent class (LC) analysis was used to subgroup farmers, based on nine managements of FR. Associations between LC and composite variables were investigated using multinomial logistic regression. Negative binomial regression was used to investigate associations between the proportion of lame sheep and composite and personality variables. The useable response rate was 32% and 97% of farmers reported having lame sheep; the geometric mean prevalence of lameness (GMPL) was 3.7% (95% CI 3.51%-3.86%). Participants grouped into three latent classes; LC1 (best practice-treat FR within 3days of sheep becoming lame; use injectable and topical antibiotics; avoid foot trimming), 11% farmers), LC2 (slow to act, 57%) and LC3 (slow to act, delayed culling, 32%), with GMPL 2.95%, 3.60% and 4.10% respectively. Farmers who reported the production cycle as a barrier to treating sheep with FR were more likely to be in LC2 (RRR 1.36) than LC1. Negative emotions towards FR were associated with higher risk of being in LC2 (RRR 1.39) than LC1. Knowledge of preventing FR spread was associated with a lower risk of being in LC2 (RRR 0.46) or LC3 (RRR 0.34) than LC1. Knowledge about FR transmission was associated with a lower risk of being in LC3 (RRR 0.64) than LC1. An increased risk of lameness was associated with the production cycle being a barrier to treating sheep with FR (IRR 1.13), negative emotions towards FR (IRR 1.13) and feelings of hopelessness towards FR (IRR 1.20). Conscientiousness (IRR 0.95) and understanding the importance of active control of lameness (IRR 0.76) were associated with reduced risk of lameness. We conclude that emotions and personality are associated with differences in farmer management of FR and prevalence of lameness. Further understanding how personality and emotions influence change in behaviour is key to increasing uptake of new information.

Analysis of behavioral changes in dairy cows associated with claw horn lesions.

Detecting lame cows is important in improving animal welfare. Automated tools are potentially useful to enable identification and monitoring of lame cows. The goals of this study were to evaluate the suitability of various physiological and behavioral parameters to automatically detect lameness in dairy cows housed in a cubicle barn. Lame cows suffering from a claw horn lesion (sole ulcer or white line disease) of one claw of the same hind limb (n=32; group L) and 10 nonlame healthy cows (group C) were included in this study. Lying and standing behavior at night by tridimensional accelerometers, weight distribution between hind limbs by the 4-scale weighing platform, feeding behavior at night by the nose band sensor, and heart activity by the Polar device (Polar Electro Oy, Kempele, Finland) were assessed. Either the entire data set or parts of the data collected over a 48-h period were used for statistical analysis, depending upon the parameter in question. The standing time at night over 12 h and the limb weight ratio (LWR) were significantly higher in group C as compared with group L, whereas the lying time at night over 12 h, the mean limb difference (△weight), and the standard deviation (SD) of the weight applied on the limb taking less weight were significantly lower in group C as compared with group L. No significant difference was noted between the groups for the parameters of heart activity and feeding behavior at night. The locomotion score of cows in group L was positively correlated with the lying time and △weight, whereas it was negatively correlated with LWR and SD. The highest sensitivity (0.97) for lameness detection was found for the parameter SD [specificity of 0.80 and an area under the curve (AUC) of 0.84]. The highest specificity (0.90) for lameness detection was present for Δweight (sensitivity=0.78; AUC=0.88) and LWR (sensitivity=0.81; AUC=0.87). The model considering the data of SD together with lying time at night was the best predictor of cows being lame, accounting for 40% of the variation in the likelihood of a cow being lame (sensitivity=0.94; specificity=0.80; AUC=0.86). In conclusion, the data derived from the 4-scale-weighing platform, either alone or combined with the lying time at night over 12 h, represent the most valuable parameters for automated identification of lame cows suffering from a claw horn lesion of one individual hind limb.

Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain.

BACKGROUND: Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor-bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. METHODS: In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n=35) or intrathecal SP-SAP (20-60 µg) in addition to standard-of-care analgesic therapy (n=35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death. RESULTS: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P<0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P<0.01). CONCLUSION: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.

Short communication: lying behavior of lactating dairy cows is influenced by lameness especially around feeding time.

Lameness is considered one of the most common welfare and productive problems in dairy cattle. The objective of this study was to evaluate differences in lying behavior between moderately lame and nonlame lactating cows under commercial conditions. Data were collected from 10 free-stall commercial herds, which were feeding on exactly the same ration once daily. All lactating cows were scored for lameness according to a 1 to 5 locomotion scoring system. Only cows with a lameness score between 1 and 4 were considered in the study. In each herd, between 10 and 15 lame cows (scored as 3 or 4) were chosen, and for each lame cow, a nonlame cow (scored as 1) within the same parity and similar days in milk was also selected. Pendant data loggers were then placed on the right hind leg of each cow for 10 d to record lying behavior at 1-min intervals. In addition, the time of feed delivery was recorded in each herd on a daily basis. Total daily lying time, daily number of lying bouts, lying bout duration, laterality (side of recumbence), and lying behavior around feed delivery time were evaluated using a mixed-effects model that accounted for the fixed effects of lameness, days in milk, parity, and the interaction between parity and lameness, plus the random effects of herd. Total daily lying time (721±24.2 min/d) tended to increase with days in milk, but it was not affected by lameness or parity. Likewise, no differences were found in the number of lying bouts (9.6±0.49/d) or laterality (47±2.6% of time lying on the right side). However, the mean bout duration was longer in lame (89.3±3.89 min) compared with nonlame (80.7±3.90 min) cows. It is interesting that lame cows stood up 13 min later than nonlame cows relative to the time when the ration was delivered. In addition, lame cows lay down 19 min earlier than nonlame ones after the feed was delivered, which implies that nonlame cows spent more time standing, and probably eating, than did lame cows. It was concluded that lame cows have longer lying bouts than nonlame animals, and that lying behavior around feed delivery time may be an effective proxy to identify moderately lame cows.

Functional and histological outcome after focal traumatic brain injury is not improved in conditional EphA4 knockout mice.

We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or sham injury and found it to be downregulated in the hippocampus (p<0.05) but not the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the behavioral and histological outcome following CCI using WT mice and Emx1-Cre-driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent in the hippocampus and markedly reduced in the cortical regions from embryonic day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had similar learning and memory abilities at 3 weeks post-TBI compared to WT controls, although brain-injured animals performed worse than sham-injured controls (p<0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod and cylinder tests of motor function up to 29 days post-injury. TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p<0.05) and hippocampal sprouting (Timm stain, p<0.05) and induced a marked loss of hemispheric tissue (p<0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.

Sensorimotor behavioral tests for use in a juvenile rat model of traumatic brain injury: assessment of sex differences.

Modeling juvenile traumatic brain injury (TBI) in rodents presents several unique challenges compared to adult TBI, one of which is selecting appropriate sensorimotor behavioral tasks that enable the assessment of the extent of injury and recovery over time in developing animals. To address this challenge, we performed a comparison of common sensorimotor tests in Long-Evans rats of various sizes and developmental stages (postnatal days 16-45, 35-190 g). Tests were compared and selected for their developmental appropriateness, scalability for growth, pre-training requirements, and throughput capability. Sex differences in response to TBI were also assessed. Grid walk, automated gait analysis, rotarod, beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer were evaluated. Grid walk, gait analysis, and rotarod failed to meet one or more of the evaluation criteria. Beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer satisfied all criteria and were capable of detecting motor abnormalities in rats subjected to controlled cortical impact on postnatal day 17. No sex differences were detected in the acute effects of TBI or functional recovery during the 28 days after injury using these tests. This demonstrates the utility of these tests for the evaluation of sensorimotor function in studies using rat models of pediatric TBI, and suggests that pre-pubertal males and females respond similarly to TBI with respect to sensorimotor outcomes.

A survey of aged horses in Queensland, Australia. Part 2: Clinical signs and owners' perceptions of health and welfare.

OBJECTIVE: To describe the prevalence and risk factors for clinical signs of disease and owner-reported health or welfare issues of aged horses in Queensland, Australia. METHODS: Owners of horses were contacted via an equestrian organisation in Queensland and asked to complete a questionnaire about their horses aged 15 years and older, to gain information about clinical signs observed in the horse and disease history. Owners were asked to identify health or welfare issues they felt were important in aged horses. RESULTS: Owners were able to identify many clinical signs of disease, with 83% of horses having at least one reported clinical sign of disease. Muscle stiffness (33%), lameness (28%), ocular discharge (22%), change in hair coat (22%) and skin problems (21%) were the most commonly reported signs. Increasing age was a risk factor for the presence of clinical signs of disease. Ponies had an increased risk of both laminitis and hirsutism, whereas Thoroughbreds had an increased risk of stereotypies, wounds, weight loss and musculoskeletal signs. Owners reported a known disease or disorder in their horses less frequently than the clinical signs of disease. Owners reported weight loss (28%), arthritis/lameness (24%) and teeth/dental care (18%) as the most important health issues, followed by welfare issues (8%). CONCLUSION: Owners demonstrated concern for the health and welfare of their aged horses, but the lack of appropriate recognition of the significance of clinical signs and limited veterinary care suggest a need for increased client communication and veterinarian-client interaction.

Behavior during transition differs for cows diagnosed with claw horn lesions in mid lactation.

Claw horn lesions, including sole hemorrhages and sole ulcers, are a major cause of lameness in dairy cattle. These lesions often develop in the weeks around calving and become visible 8 to 12 wk later. The aim was to determine whether cows that are diagnosed with claw horn lesions several weeks after calving behave differently during the calving period when the lesions are thought to first develop. The claws of 26 multiparous Holstein dairy cows were scored for sole hemorrhage severity and presence of sole ulcers 2 wk before calving, 3 wk after calving, and every 4 wk thereafter until 15 wk after calving. Of the 26 cows, 13 cows had no or low lesion scores up to 15 wk and 13 cows had at least 1 new severe lesion or sole ulcer diagnosed between 7 and 15 wk after calving. Behavior (dry matter intake, feeding time and rate, number and size of meals, standing time, number and duration of standing bouts, location of standing, and displacements at the feed bunk) was recorded from 2 wk before calving to 3 wk after calving. Behavior during the 2 wk before calving, first 24h after calving, 1 wk after calving, and 2 to 3 wk after calving was compared between cows with and without lesions in mid lactation. Multivariate regression was used to determine the predictive value of each behavior and combination of behaviors on lesion diagnosis. Cows diagnosed with lesions in mid lactation spent more time standing than cows without lesions during the 2 wk before (832+/-29 vs. 711+/-29 min/d) and 24 h after (935+/-46 vs. 693+/-46 min/d) calving. These differences were driven by an increase in the time spent perching with front feet in the stall (241+/-22 vs. 147+/-22 min/d at 2 wk before calving) and an increase in standing bout duration (101+/-10 vs. 56+/-10 min/bout at 24 h after calving). Compared with cows without lesions, cows with lesions consumed feed at a faster rate (86+/-3 vs. 77+/-3 g/min) during the 2 wk before calving and consumed more feed (17.9+/-0.9 vs. 12.3+/-0.9 kg/d) during the 24 h after calving. The number of displacements at the feeder was not different between groups. These results indicate that a combination of feeding and standing behavior during the transition can serve as early indicators of claw horn lesions in mid lactation.

Spinally applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis.

Inflammation causes sensitization of peripheral and central nociceptive neurons. Pharmacological modulation of the latter has successfully been used for clinical pain relief. In particular, inhibitors of the NMDA glutamate receptor such as ketamine and agonists at the mu-opioid receptor such as morphine are broadly used. Besides driving the propagation of pain signals, spinal mechanisms are also discussed to modulate inflammation in the periphery. Here, we tested the hypothesis that intrathecally applied ketamine or morphine not only reduce pain-related behavior, but also attenuate induction and maintenance of the inflammatory response in a model of chronic antigen-induced arthritis (AIA). Ketamine, morphine or vehicle was applied to the spinal cords of anesthesized animals with AIA. Swelling and histopathological changes were assessed after 6h (acute phase). Intrathecal catheters were implanted in another set of animals with AIA and substances were applied continuously. During the observation period of 21 days, inflammation and pain-related behavior were assessed. Ketamine and morphine significantly reduced arthritis severity as indicated by reduced joint swelling, but even more intriguingly by reduced infiltration with inflammatory cells and joint destruction in the acute and the chronic phase of arthritis. Morphine showed strong antinociceptive effects in the acute phase only, while the newly established effective dose for ketamine in a continuous application design reduced hyperalgesia in the acute and the chronic stage. In conclusion, both compounds exhibit anti-inflammatory effects during induction and maintenance of arthritis when applied intrathecally. These data thus propose a role of spinal NMDA- and opioid-receptors in the neuronal control of immune-mediated inflammation.

Detrimental effects of aging on outcome from traumatic brain injury: a behavioral, magnetic resonance imaging, and histological study in mice.

Considerable evidence indicates that outcomes from traumatic brain injury (TBI) are worse in the elderly, but there has been little preclinical research to explore potential mechanisms. In this study, we examined the age-related effects on outcome in a mouse model of controlled cortical impact (CCI) injury. We compared the responses of adult (5-6 months old) and aged (21-24 months old) male mice following a moderate lateral CCI injury to the sensorimotor cortex. Sensorimotor function was evaluated with the rotarod, gridwalk and spontaneous forelimb behavioral tests. Acute edema was assessed from hyperintensity on T2-weighted magnetic resonance images. Blood-brain barrier opening was measured using anti-mouse immunoglobulin G (IgG) immunohistochemistry. Neurodegeneration was assessed by amino-cupric silver staining, and lesion cavity volumes were measured from histological images. Indicators of injury were generally worse in the aged than the adult mice. Acute edema, measured at 24 and 48 h post-injury, resolved more slowly in the aged mice (p < 0.01). Rotarod recovery (p < 0.05) and gridwalk deficits (p < 0.01) were significantly worse in aged mice. There was greater (p < 0.01 at 3 days) and more prolonged post-acute opening of the blood-brain barrier in the aged mice. Neurodegeneration was greater in the aged mice (p < 0.01 at 3 days). In contrast, lesion cavity volumes, measured at 3 days post-injury, were not different between injured groups. These results suggest that following moderate controlled cortical impact injury, the aged brain is more vulnerable than the adult brain to neurodegeneration, resulting in greater loss of function. Tissue loss at the impact site does not explain the increased functional deficits seen in the aged animals. Prolonged acute edema, increased opening of the blood-brain barrier and increased neurodegeneration found in the aged animals implicate secondary processes in age-related differences in outcome.

Changes of cytoskeletal proteins in nerve tissues and serum of rats treated with 2,5-hexanedione.

To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), male Wistar rats were administrated HD at dosage of 200 or 400mg/kg for 8 weeks (five-times per week). All rats were sacrificed after 8 weeks of treatment and the cerebrum cortex (CC), spinal cord (SC) and sciatic nerves (SN) were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilaments (NFs) subunits (NF-L, NF-M and NF-H) in nerve tissues of 200 and 400mg/kg HD rats significantly decreased in both the supernatant and pellet fractions. Furthermore, significant negative correlations between NFs levels and gait abnormality were observed. As for microtubule (MT) and microfilament (MF) proteins, the levels of alpha-tubulin, beta-tubulin and beta-actin in the supernatant and pellet fraction of SN significantly decreased in 200 and 400mg/kg HD rats and correlated negatively with gait abnormality. However, the contents of MT and MF proteins in CC and SC were inconsistently affected and had no significant correlation with gait abnormality. The levels of NF-L and NF-H in serum significantly increased, while NF-M, alpha-tubulin, beta-tubulin and beta-actin contents remain unchanged. A significant positive correlation (R=0.9427, P<0.01) was observed between gait abnormality and NF-H level in serum as the intoxication went on. These findings suggested that HD intoxication resulted in a progressive decline of cytoskeletal protein contents, which might be relevant to the mechanisms of HD-induced neuropathy. NF-H was the most sensitive index, which may serve as a good indicator for neurotoxicity of n-hexane or HD.

Influence of CGS 21680, a selective adenosine A(2A) agonist, on the phencyclidine-induced sensorimotor gating deficit and motor behaviour in rats.

RATIONALE: Recently it has been suggested that adenosine A(2A) receptor agonists may be potential antipsychotic drugs. It is, however, not clear whether these compounds may exert their antipsychotic effect without producing extrapyramidal side-effects (e.g. catalepsy, muscle rigidity, ataxia). It is known that such side-effects may be due to overactivation of the GABAergic strio-pallidal pathway, which may be estimated as an increased expression of proenkephalin (PENK) mRNA in the striatum. OBJECTIVE: The aim of this study was to determine whether CGS 21680, a selective adenosine A(2A) receptor agonist, can reverse the disruption of prepulse inhibition (PPI) of the acoustic startle response induced by the non-competitive antagonist of NMDA receptors phencyclidine (PCP) without producing motor side-effects in rats. RESULTS: Systemic administration of PCP (5 mg/kg) produced profound reduction of the PPI, which was reversed by CGS 21680 (1 mg/kg). CGS 21680 (0.1 and 1 mg/kg) was without effect on catalepsy, muscle rigidity and rotarod performance in rats as well as on the PENK mRNA expression in the striatum estimated by in situ hybridization. Only after the highest dose used (5 mg/kg) were signs of catalepsy (measured using a 9-cm cork test), disturbed balance and a loss of hind limb control (measured in the rotarod test) seen. Moreover, increased muscle resistance during passive extension measured mechanomyographically after this dose of CGS 21680 was observed. CONCLUSIONS: The present results support the hypothesis that adenosine A(2A) receptor agonists may be potentially useful antipsychotic agents with the low incidence of extrapyramidal side-effects.

Healing action of nerve growth factor on lameness in adult goats.

We investigated the effect of nerve growth factor in goats affected by lameness, a condition that is associated with cutaneous ulcers, abscesses and granulomas. Lesions were treated daily with 1 microgram of nerve growth factor (NGF), dissolved in 100 microliters of sesame oil or with sesame oil only. Healthy controls were treated with sesame oil only for periods ranging from two to four weeks and behavioral, biochemical and histopathological conditions were evaluated. Topical application of NGF, but not sesame oil, promoted ulcer healing in all goats within two-three weeks of treatment. The effect of NGF was to re-establish in about 60 days normal locomotion and indirectly to improve feeding behavior and milk production. These findings suggest that NGF might be clinically useful for healing damaged skin in goats and confirm previous studies on human corneal ulcers.