Alzheimer’s-like changes in the brain

first_imgThe association of the inhaled anesthetic isoflurane with Alzheimer’s-disease-like changes in mammalian brains may by caused by the drug’s effects on mitochondria, the structures in which most cellular energy is produced. In a study that will appear in Annals of Neurology and has received early online release, Harvard-affiliated Massachusetts General Hospital (MGH) researchers report that administration of isoflurane impaired the performance of mice on a standard test of learning and memory — a result not seen when another anesthetic, desflurane, was administered. They also found evidence that the two drugs have significantly different effects on mitochondrial function.“These are the first results indicating that isoflurane, but not desflurane, may induce neuronal cell death and impair learning and memory by damaging mitochondria,” says Yiying (Laura) Zhang, a research fellow in the MGH Department of Anesthesia, Critical Care and Pain Medicine and the study’s lead author. “This work needs to be confirmed in human studies, but it’s looking like desflurane may be a better anesthetic to use for patients susceptible to cognitive dysfunction, such as Alzheimer’s patients.”Previous studies have suggested that undergoing surgery and general anesthesia may increase the risk of Alzheimer’s, and it is well known that a small but significant number of surgical patients experience a transient form of cognitive dysfunction in the postoperative period. In 2008, members of the same MGH research team showed that isoflurane induced Alzheimer’s-like changes — increasing activation of enzymes involved with cell death and generation of the A-beta plaques characteristic of the disease — in the brains of mice. The current study was designed to explore the underlying mechanism and behavioral consequences of isoflurane-induced brain cell death and to compare isoflurane’s effects with those of desflurane, another common anesthetic that has not been associated with neuronal damage.In a series of experiments, the investigators found that the application of isoflurane to cultured cells and mouse neurons increased the permeability of mitochondrial membranes; interfered with the balance of ions on either side of the mitochondrial membrane; reduced levels of ATP, the enzyme produced by mitochondria that powers most cellular processes; and increased levels of the cell-death enzyme caspase. The results also suggested that the first step toward isoflurane-induced cell death was increased generation of reactive oxygen species — unstable oxygen-containing molecules that can damage cellular components. The performance of mice on a standard behavioral test of learning and memory declined significantly two to seven days after administration of isoflurane, compared with the results of a control group. None of the cellular or behavioral effects of isoflurane were seen when the administered agent was desflurane.In another study by members of the same research team — appearing in the February issue of Anesthesia & Analgesia and published online in November — about one-quarter of surgical patients receiving isoflurane showed some level of cognitive dysfunction a week after surgery, while patients receiving desflurane or spinal anesthesia had no decline in cognitive performance. That study, conducted in collaboration with investigators from Beijing Friendship Hospital in China, enrolled only 45 patients — 15 in each treatment group — so its results need to be confirmed in significantly larger groups.“Approximately 8.5 million Alzheimer’s disease patients worldwide will need anesthesia and surgical care every year,” notes Zhongcong Xie, corresponding author of both studies, director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine, and an associate professor of anesthesia at Harvard Medical School (HMS).“Developing guidelines for safer anesthesia care for these patients will require collaboration between specialists in anesthesia, neurology, geriatric medicine, and other specialties. As the first step, we need to identify anesthetics that are less likely to contribute to Alzheimer’s disease neuropathogenesis and cognitive dysfunction,” Xie adds.last_img read more

Great Dane | Q & A with Paddling World Champ Dane Jackson

first_imgDane Jackson has had one epic year. The 22-year-old pro-kayaker from Tennessee won more events in 2015 than most do in a lifetime, interspersing the races and freestyle comps between a first descent in Mexico and other expedition adventures.Jackson also continues a legacy set forth by his father, world-renowned freestyle champion and kayak company founder Eric Jackson. Alongside him on the family tree is his sister Emily, also a longtime dominant force in women’s rodeo.As he was driving home to Rock Island, Tenn., from a family vacation, Jackson took the time to explain what factors made his 2015 season the strongest one yet and his plans to make 2016 even better.Summarize how this season went for you.Best season ever. Normally, I’d win just a few events, but this year I had only three results out of the 15 or 20 this season that I didn’t come out on top. Obviously, winning the ICF Freestyle Canoe World Championship on the Ottawa this season was the cherry on top. Besides that, at the GoPro Mountain Games, I won both the Men’s Freestyle and the downriver Steep Creek Championship. No one has done that before.How much do you devote to training? Not any, really. Kayaking is fun. As soon as you’re stressing, you’re never going to do as well. When it comes to Worlds, I definitely get a little stressed because I want to do as well as I can. But I don’t let that stress take away from that week of fun and paddling. My mentality for upcoming events is I have to relearn stuff, and that helps with my results.How has that approach helped you in competing?I feel strongest and am most known for freestyle, but the last couple of years, I’ve been trying to make a name in racing. That year was the Whitewater Grand Prix in Chile, and I didn’t think I had a chance to win because there wasn’t freestyle, so I didn’t have an edge. I also realized that my forward stroke was not as powerful as the others. Mostly it was less sprinting, and more like I needed to learn the forward stroke. So I worked on it, and that helped me in all the races since.What’s it like coming from a family of champion paddlers?My dad is the reason I’m a kayaker. He won his first World Championship title in 1993 and was a full-time kayaker when I arrived. From the beginning, he made it very clear he wanted it to be fun, a mentality he was really good at living by. I wanted to be like him. Instead of this being his sport that he does, he made a point to teach us and make it a family event. So we all paddled together and grew together. That’s the way he raised us, and my mom, too, because she was always there and supported him. I don’t know where we’d be if it weren’t for all they did.What are your relationships with the rest of your family?My sister and I pretty much just had each other growing up. Emily and I have a great relationship. Growing up, we paddled together, watched movies, played games. We’d play a dice game or Settlers of Katan; we used to play Life a lot, too, when we were kids. I guess I was more of an annoying little brother to her husband Nick, who’s been traveling with the family since he was 15.Where do you see yourself going? The next season, I plan to win even more races and head back to Veracruz and Chiapas. There’s possibly something in Hawaii, too.boxers or briefs?It depends on what I’m feeling. Boxers probably? It’s hard for me to go for tight stuff. My dad thinks Speedos are making a comeback and has Speedo Thursday where he’s in a Speedo.Are they?No, no, they’re not making a comeback. My dad doesn’t care what people think, and that’s probably how he got where he is. But that also means he wears Speedos.[divider]read more on[/divider]last_img read more