Traumatic brain injuries are known to trigger a variety of symptoms ranging from a simple headache to permanent memory and thinking problems. Now scientists at UCLA have discovered that a traumatic brain injury can result in the loss of a specific type of neuron, elevating the risk for Parkinson’s disease as well.
During a preclinical study, scientists found that a moderate traumatic brain injury in rats caused an initial 15 percent loss in nigrostriatal dopaminergic neurons, and that these brain cells continued to decline after the injury, leading to a 30 percent loss 26 weeks later.
A lack in these specific neurons can result in the trademark motor problems found in Parkinson’s patients, including akinesia (problems with movement), postural tremor and rigidity. Furthermore, when combined with the pesticide paraquat — a second known risk factor for Parkinson’s — the loss of dopaminergic neurons climbed to 30 percent at a much faster rate.
The study was conducted by first author Che Hutson, Ph.D., and senior author Dr. Marie-Francoise Chesselet, a professor of neurology and chair of the UCLA Department of Neurobiology, along with colleagues.
Although traumatic brain injury was already known as a risk factor for Parkinson’s, scientists didn’t know exactly why. Nor was it known whether traumatic brain injury worked synergistically with pesticides such as paraquat, one of the world’s most commonly used herbicides, known to be toxic to human beings and animals and also linked to Parkinson’s.
Nigrostriatal dopaminergic neurons play a role in the production of dopamine, which is involved in the regulation of movement, among other things. The current research suggests that while a traumatic brain injury does not cause Parkinson’s, it can make individuals more susceptible to the disorder, said Chesselet.
“We found that with a moderate traumatic brain injury, the loss of neurons was too small in number to cause Parkinson’s disease, but it is enough to increase the risk of PD,” she said. “By decreasing the number of dopaminergic neurons, any further insult to the brain will be attacking a smaller number of neurons; as a result, the threshold for symptoms would be reached faster.”
Chesselet noted, “shortly after a traumatic brain injury, these neurons are more vulnerable to a second insult.”
The study took into account both the long-term effects of traumatic brain injury, as well as the short-term effects when combined with a low dose exposure to paraquat. In the short-term effect study, rats who received moderate traumatic brain injury alone experienced a 15 percent loss of dopaminergic neurons. When paraquat exposure was added, the loss increased to 30 percent.
For the long-term study (which did not include paraquat), the rats experienced a 30 percent loss of dopaminergic neurons 26 weeks after the initial injury. This suggests that in the long term, traumatic brain injury alone is enough to trigger a progressive degeneration of dopaminergic neurons.
“These are the first data revealing that in a model of experimental traumatic brain injury, not only do nigrostriatal dopaminergic neurons degenerate, those that survive become sensitized to paraquat toxicity,” said study author Dr. David A. Hovda, a professor of neurosurgery and director of the UCLA Brain Injury Research Center.
“These results suggest that greater attention should be given to the long-term risk of Parkinson’s after traumatic brain injury, and that the epidemiology of both risk factors, brain injury and exposure to paraquat, should be evaluated in combination,” Chesselet said.
The study appears in the online edition of the journal Neurotrauma.
Source: University of California