Healthy welders may be at increased risk for early brain damage

ScienceDaily (Apr. 6, 2011) — New research suggests that workers exposed to welding fumes may be at risk for developing brain damage in an area of the brain also affected in Parkinson's disease. The study is published in the April 6, 2011, online issue of Neurology®, the medical journal of the American Academy of Neurology.

See Also:Health & MedicineParkinson's ResearchBrain TumorNervous SystemMind & BrainParkinson'sDisorders and SyndromesBrain InjuryReferenceDementia with Lewy bodiesEssential tremorNeurologyBrain damage

Fumes produced by welding contain manganese. Manganese is a chemical element that, even at low levels, has been linked to neurologic problems, including Parkinson's disease-like symptoms.

"There are over one million workers who perform welding as part of their job functions in the United States," said Brad A. Racette, MD, with Washington University School of Medicine in St. Louis and a Fellow with the American Academy of Neurology. "If a link between neurotoxic effects and these fumes were proven, it would have a substantial public health impact for the U.S. workforce and economy."

The study involved 20 welders with no symptoms of Parkinson's disease, 20 people with Parkinson's disease who were not welders and 20 people who were not welders and did not have Parkinson's. The welders were recruited from two Midwest shipyards and one metal fabrication company. All participants were given brain PET and MRI scans, motor skills tests and examined by a neurologist who specializes in movement disorders. The welders had an average of 30,000 hours of lifetime welding exposure. Their average manganese levels were found to be two times the upper limits of normal.

Scientists found that welders had an average 11.7 percent reduction in a marker of dopamine in one area of the brain on PET scans as compared to people who did not weld. Dopamine is a chemical messenger that helps nerve cells communicate and is decreased in specific brain regions in people with Parkinson's disease. The welders' motor skills test scores also showed mild movement difficulties that were about half of that found in the early Parkinson's disease patients.

"While these changes in the brain and dopamine dysfunction may be an early marker of neuron death related to welding exposure, the damage appeared to be different from those of people with full-fledged Parkinson's disease," said Racette. "MRI scans also revealed brain changes in welders that were consistent with manganese deposits in the brain."

"Although this study shows that these workers had dopamine dysfunction in the brain, the study authors could not determine whether this was specifically related to manganese," said W. R. Wayne Martin, MD, who wrote an accompanying editorial on the topic. Martin is with the University of Alberta in Edmonton, Alberta, Canada and a member of the American Academy of Neurology. "Will these individuals develop full-fledged Parkinson's disease? We can't answer that question based on the study but more research should be done to explore this possibility."

The study was supported by the Michael J. Fox Foundation, the National Institutes of Health, the American Parkinson Disease Association, Advanced Research Center at Washington University, the Great St. Louis Chapter of the ADPA, the McDonnell Center for Higher Brain Function and the Barnes-Jewish Hospital Foundation.

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Anti-depressants boost brain cells after injury in early studies

ScienceDaily (Apr. 22, 2011) — Anti-depressants may help spur the creation and survival of new brain cells after brain injury, according to a study by neurosurgeons at the University of Rochester Medical Center.

See Also:Health & MedicineBrain TumorNervous SystemBirth DefectsMind & BrainBrain InjuryDisorders and SyndromesIntelligenceReferenceBrain damageCerebral contusionHead injuryEncephalopathy

Jason Huang, M.D., and colleagues undertook the study after noticing that patients with brain injuries who had been prescribed anti-depressants were doing better in unexpected ways than their counterparts who were not taking such medications. Not only did their depression ease; their memory also seemed improved compared to patients not on the medication.

"We saw these patients improving in multiple ways -- their depression was improved, but so were their memory and cognitive functioning. We wanted to look at the issue more, so we went back to the laboratory to investigate it further," said Huang, associate professor of Neurosurgery and chief of Neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center.

The team's findings were published online recently in the Journal of Neurotrauma.

Huang said many patients who have a traumatic brain injury also experience depression -- by some estimates, half of such patients are depressed. Doctors aren't sure whether the depression is a byproduct of the sudden, unfortunate change in circumstances that patients find themselves in, or whether the depression is a direct consequence of brain damage.

Previous research by other groups indicated that anti-depressants help generate new brain cells and keep them healthy in healthy animals. That, together with the experience of his patients, led Huang to study the effects of the anti-depressant imipramine (also known as Tofranil) on mice that had injuries to their brains.

Scientists found that imipramine boosted the number of neurons in the hippocampus, the part of the brain primarily responsible for memory. By one measure, mice treated with imipramine had approximately 70 percent more neurons after four weeks than mice that did not receive the medication.

That change was borne out on behavioral tests as well. The team tested mice by using what scientists call a novel object recognition test. Like human infants, mice tend to spend more time sizing up objects that they haven't encountered before -- or don't remember encountering -- than they do objects that they've seen before. This gives scientists a way to measure a mouse's memory.

The team found that mice that had been treated with imipramine had a better memory. They were more likely to remember objects they had seen previously and so spent more time exploring truly novel objects, compared to mice that did not receive the compound.

The benefits did not extend to the motor skills of the mice -- a finding that parallels what neurosurgeons like Huang have seen in their patients on anti-depressants, who don't show improved mobility after use of the medications.

Scientists aren't sure whether the drug helps spur the creation of more new neurons, or whether it helps newly created neurons survive -- or both. Some of the team's evidence indicates that the drug helps immature stems evolve into useful cells such as neurons and astrocytes, and to travel to the exact areas of the brain where they're needed.

In addition to sorting out those questions, investigators will try to identify the molecular pathway that prompts the brain to create more neurons in response to anti-depressants. The team suspects that a molecule known as BDNF or brain-derived neurotrophic factor may play a role.

Huang notes that one of his mentors, co-author Douglas H. Smith, M.D., of the University of Pennsylvania, has found that a brain injury itself also seems to prompt the brain to create more brain cells, perhaps as a way to compensate for injury.

"The brain has an intrinsic mechanism to repair itself to a certain extent," said Huang. "Our goal is to learn more about that mechanism and improve it, to help patients recover even more brain function than they can now, even with extensive work and rehabilitation."

Some of Huang's work is based on his experiences treating soldiers and civilians while working for four months as a neurosurgeon with the U.S. Army Reserve in Iraq, as well as more than a decade of experience treating patients affected by incidents like motor vehicle accidents.

He said that traumatic brain injury -- an injury experienced by approximately 1.4 million Americans each year -- must be treated aggressively. Often this involves surgery to relieve pressure on the brain, other procedures to protect the brain against immediate further injury, and then rehabilitation for months or years.

"It's exciting that the study involves a drug that is already safe and approved by FDA and is used clinically. If we could add a medication to the treatment regimen -- even a slight improvement would be a big gain for these patients. It's our hope that the work will ultimately make a difference in patient care," added Huang, who is also a scientist in the Center for Neural Development and Disease.

In addition to Huang, other authors at Rochester include post-doctoral associates Xiaodi Han, M.D., Ph.D., Jing Tong, M.D., and Jiankai Yang, M.D.; neurosurgery resident Arash Farahvar, M.D.,; and undergraduate Ernest Wang. Other authors include Jun Zhang, M.D., of the Chinese PLA General Hospital in Beijing; Uzma Samadani, M.D., Ph.D., of New York University; and Douglas H. Smith, M.D., of the University of Pennsylvania.

The work was funded by the National Institute of Neurological Disorders and Stroke and by the University of Rochester.

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