Description of the incidence, clinical presentation and outcome of proximal limb and pelvic fractures in Hong Kong racehorses during 2003-2014.

BACKGROUND: Few studies have described incidences of proximal limb and pelvic fracture (PLPF) in Thoroughbred racehorses occurring on race day and during training. Information regarding clinical presentations and future racing careers in cases of PLPF is limited. OBJECTIVES: To describe the incidence, clinical presentation and outcome of PLPF sustained by horses in racing and training at the Hong Kong Jockey Club (HKJC) between 2003 and 2014. STUDY DESIGN: Retrospective cohort study. METHODS: Horses with PLPF confirmed by nuclear scintigraphy, ultrasonography, radiography or post-mortem examination were identified using veterinary clinical records. Training and racing data for case horses were described. Incidences of fractures were estimated per 1000 horses in training and per 1000 race starts for fractures sustained during racing. Descriptive statistics were used to describe the study population. RESULTS: A total of 129 instances of PLPF were sustained by 108 racehorses. The most commonly fractured bone was the humerus (49.6%), followed by the tibia (29.4%). Nine horses sustained fatal fractures, eight of which occurred during racing. The incidence of fracture during racing was 0.30 per 1000 starts. Two-thirds of fractures occurred during training. The majority of horses presented with grade 3 lameness (n = 42 of 119 injury events, 35.3%). All horses presenting with grade 5 lameness sustained fatal injuries. Following noncatastrophic injury, all horses underwent box rest and 81 horses subsequently resumed racing; 45 of these won a race. Horses were retired at a median of 25 months (interquartile range: 15-36 months) after injury. MAIN LIMITATIONS: Protocols for resting non-training racehorses at the HKJC and for recording rehabilitation regimens post-injury prevented the calculation of horse days at risk. CONCLUSIONS: The incidence of PLPF at the HKJC is low. Non-fatal PLPF is not necessarily a career-ending injury and many horses resume racing successfully following conservative treatment.

HFS-induced long-term potentiation and LFS-induced depotentiation in area CA1 of the hippocampus are not good models for learning.

Spatial learning in rats has been shown to be dependent on the intact hippocampus and lesioning this region impairs learning performance. Long-term potentiation (LTP) and depotentiation (DP) of synaptic transmission have been suggested to model memory formation at the neuronal level. Recently it was shown that LTP in the dentate gyrus or area CA3 of the hippocampus is not essential for the ability to learn a spatial water maze task. Here we show that the metabotropic glutamate receptor agonist (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD), which acts predominantly at presynaptic sites, only marginally impaired spatial learning in a water maze or radial arm maze (three out of eight arms baited) when injected ICV (5 microliters of a 20 mM solution). There also were small impairments in non-spatial and visual discrimination tasks, indicating that the small learning impairments were due to nonselective effects of the drug. The same dose depressed field EPSPs and completely blocked LTP induced by high-frequency stimulation (HFS, 200 Hz) in the CA1 region of the rat hippocampus in vivo. A lower (5 microliters of a 10 mM solution) dose did not depress baseline but still blocked LTP. Injecting the same dose after induction of LTP blocked DP induced by low-frequency stimulation (LFS, 10 Hz). These results indicate that neither HFS-induced LTP nor LFS-induced DP in area CA1 are good models for the induction of synaptic changes that might underlie spatial learning in the rat.

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

We report here that release of glutamate, inositol phospholipid metabolism, and protein kinase C (PKC) activity are increased in synaptosomes prepared from hippocampi of rats that had been trained in a spatial learning task. In hippocampi obtained from animals that were untrained, activation of the metabotropic glutamate receptor by the specific agonist trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD) increased release of glutamate but only in the presence of a low concentration of arachidonic acid. A similar interaction between arachidonic acid and ACPD was observed on inositol phospholipid turnover and on PKC activity. However, the synergistic effect of arachidonic acid and ACPD on glutamate release was occluded in hippocampal synaptosomes prepared from trained rats. Occlusion of the effect on inositol phospholipid turnover and PKC activation was also observed. These data suggest that the molecular changes that underlie spatial learning may include activation of metabotropic glutamate receptors in the presence of arachidonic acid and that the interaction between arachidonic acid and ACPD triggers the presynaptic changes that accompany learning.

L-AP4 (L-(+)-2-amino-4-phosphonobutyric acid) induced impairment of spatial learning in the rat is antagonized by MAP4 ((S)-2-amino-2-methyl-4-phosphonobutanoic acid).

L-AP4, an agonist at the metabotrophic glutamate receptors 4, 6, 7, 8 and 9 produced a selective spatial learning impairment in a water maze as well as in an 8-arm maze task when injected i.c.v. (5 microliters of a 80 mM solution), a dose previously reported to block consolidation of long-term potentiation in vivo. Acquisition and recall of the spatial water-maze task, as measured by escape latency and quadrant bias, respectively, were impaired, whereas swim speed was not affected. In contrast, ability to perform a non-spatial control task was not impaired; latency to reach a visible escape platform was not delayed in L-AP4-treated animals. No behavioral difference was visible in the open field. MAP4, an antagonist of mGluRs mediating L-AP4 induced reduction of transmitter release, when administered pretraining i.c.v. (5 microliters of an 80 mM solution) did not affect motor activity in the open field test but did impair learning of both spatial tasks. In addition, swim speed was increased. However, injecting L-AP4 and MAP4 in combination at equimolar concentrations had no effect on learning in both spatial tasks or on swim speed in the water maze. Neither latency in the visible-platform test nor behavior in the open field was affected. We conclude that L-AP4 sensitive metabotropic glutamate receptors play a selective role in learning and memory formation of the rat.

7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Nitric oxide (NO) is an intercellular messenger that has been suggested to have a role in learning and memory formation. Previous studies with nonselective NO synthase inhibitors have produced contradictory results in learning experiments. However, these drugs also produced blood pressure changes, as NO is an endothelial-derived relaxing factor. A novel NO synthase inhibitor, 7-nitro indazole (7-NI), as a dose (30 mg/kg i.p.) shown previously to inhibit neuronal NO synthase by 85% without affecting blood pressure, produced amnesic effects both in a water maze and in an 8-arm radial maze. Latency as well as distance was greater in the 7-NI group in the water maze while swim speed was not affected. Latency, working memory (WM), and reference memory (RF) errors were also higher in the 7-NI group in the 8-arm maze. At the end of the second training day, these differences were no longer apparent. However, on the fourth training day, a transfer test in the water maze showed that 7-NI had produced a spatial memory deficit, reducing quadrant bias and the number of annulus crossings. Learning of a visual cue task was not affected. No difference between groups was visible in an open field test. We conclude that neuronal NO synthase activity plays a role in learning and memory formation in the rat.