The Horse

OCT 2018

The Horse:Your Guide To Equine Health Care provides monthly equine health care information to horse owners, breeders, veterinarians, barn/farm managers, trainer/riding instructors, and others involved in the hands-on care of the horse.

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36 October 2018 The Horse | TheHorse.com Inflammation and the Brain Cytokines from whole-body inflam- mation can signal the brain to induce sickness behavior. "There are receptors for TNFα and interleukins within blood vessels in the brain," says Suagee-Bedore. "These cells respond to stimulation by activating production of cyclooxygenase (COX, an enzyme responsible for produc- ing prostaglandins that contribute to the inflammatory process). COX then signals production of prostaglandin E2—its release into the brain side of the blood/ brain barrier initiates fever and other sickness behaviors." Signs such as fever, lack of appetite, and lethargy aren't often associated with low-grade chronic inflammation, indicating that low cytokine levels don't signal the brain's sickness behavior mechanism. Bodywide inflammation related to leaky gut syndrome can have other behavioral effects. For example, a horse might appear calm and reliable but, if you reach to touch him, he becomes resistant and belligerent. Such "irrecon- cilable" behavior might have to do with a breached blood-brain barrier (normally, tight junctions between red blood cells in brain tissue carefully control what can pass through the bloodstream into the brain). Inflammatory mediators passing from the gut to the systemic circulation to the brain can alter behavioral respons- es to stimuli, says Suagee-Bedore. Recent research has demonstrated that maternal obesity affects metabolism and increases inflammation in both dam and foal. For example, at 12 months of age, osteochondrosis (abnormal ossifi- cation of cartilage) was more prevalent in foals born to obese mares than foals from mares with normal body condition scores. Study results in humans and rats show that maternal obesity elicits signs of brain inflammation in offspring, leading to anxiety, behavioral abnormalities, and learning difficulties. In growing horses this has the potential to spawn behavioral problems that could carry over to their performance careers. Effects of Exercise Athletic horses have a reduced risk of developing insulin resistance because even minimal amounts of exercise increase insulin sensitivity, says Suagee- Bedore. Yet, inflammation affects skeletal muscle because it's a repository for glycogen storage, as well as a functional structure of locomotion. The mechanical forces associated with exercise cause skeletal muscle to produce pro-inflammatory cytokines, says David Horohov, PhD, chair of the department of veterinary science and director of the University of Kentucky's Gluck Equine Research Center, in Lexington. While low-level inflammation associated with tissue repair is not detrimental—in fact, some inflammation post-exercise is nor- mal, leading to muscle and bone adapta- tion and healing—elevated or chronic inflammation can lead to muscle tissue damage and scarring, he explains. Transient muscle soreness can lead to temporary increases in bodywide inflammatory responses, he says, but these resolve quickly without needing intervention. In one study Horohov and col- leagues identified an increase in pro-inflammatory cytokine expression two hours following exercise. They fed half of 25 2-year old Thoroughbreds a nutritional supplement containing bo- swellia (Indian frankincense), curcumin (a chemical produced by turmeric and other plants), coenzyme (CoQ10, an antioxidant the body produces), glycine propionyl-L carnitine (GPLC, an amino acid the body produces), and ribose (a sugar that makes up RNA, which is important for protein synthesis). Supple- mented horses had significantly lower pro-inflammatory cytokine expression following exercise and adapted to train- ing better than nonsupplemented horses. Improved adaptation equates to less risk for injury. "It is thought that the supplement reduces free radical production, a normal byproduct of oxidative exercise," says Horohov. "This then prevents oxidative damage to cell membranes and DNA, which in turn reduces signals for pro- inflammatory gene expression." Consequences of Anti-Inflammatory Drugs Horses often receive non-steroidal anti- inflammatory drugs (NSAIDs) to combat inflammation, pain, and lameness. But this is not without consequence. "By masking pain, overuse of NSAIDs allows an injured horse to continue working de- spite incurring more structural damage," Horohov says. "Also, mild inflammation plays an important role in the repair process; interference by NSAIDs in this process delays healing and interferes with repair mechanisms. "NSAIDs may also interfere with nor- mal physiologic adaptations to exercise," he continues. "When the rate of exercise- induced damage (which can occur normally post-exercise to a certain extent) exceeds the healing capacity of the tis- sue, the result is excessive inflammation, which undoubtedly leads to an increased risk for injury." Long-term NSAID administration also increases intestinal permeability (that leaky gut) significantly, says Horohov. This puts the horse at risk for a systemic inflammatory response to leaked bacte- rial endotoxin (LPS). "Since NSAID administration is thought to lead to ulcer formation, omeprazole, a proton pump inhibi- tor (PPI) drug, is frequently given with NSAIDs," he says. "However, studies have shown the opposite effect, with PPI drugs actually exacerbating NSAID-induced intestinal damage." Researchers believe this to be due to significant shifts in intestinal microbial populations. Take-Home Message The ways we feed and keep our horses have a profound effect on their overall health. Many triggers lead to bodywide inflammation, with stress, obesity, high- starch and -sugar diets, intense exercise, and NSAIDs leading the charge. Good horse-keeping and nutritional practices are instrumental in preventing many problems that could ultimately result in bodywide inflammation. Looking at the body holistically can give us a new per- spective on management strategies. h IT'S ALL CONNECTED NSAID administration can interfere with normal repair mechanisms

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