AUG. 26, 2005 | When the central nervous system is injured, a common mechanism may be for the brain to revert back to an early developmental stage, says a University of Arkansas for Medical Sciences (UAMS) researcher.

His continued exploration of this hypothesis could lead Edgar Garcia-Rill, Ph.D., to treatments as varied as allowing the paralyzed to walk or a way to realign arousal processes to help those suffering from schizophrenia or depression.

Garcia-Rill was chosen as the 2005 UAMS Distinguished Faculty Scholar for his varied research program and extensive mentoring experience.

The Distinguished Faculty Scholar Award recognizes outstanding faculty whose contributions to academic medicine have brought honor and prestige to the College of Medicine. The honor includes a lecture presented by the distinguished faculty scholar to the faculty, a dinner with faculty and students and a cash award. The college established the award in 1993.

Garcia-Rill’s lecture Aug. 2 was part of the Dean’s Distinguished Lecture Series. He used the lecture not to promote his work but to appeal to colleagues to consider how their work and interests could advance collaborations based on this research.

“We need some help and this is an opportunity to forge new collaborations that could lead in exciting new directions,” Garcia-Rill said to open his presentation. “There is some very nice potential for new clinical interventions or treatments.”

In his lecture, “Two Stories of Regression in Response to CNS Insult: Coupling the Wagons,” Garcia-Rill detailed two case studies in support of his hypothesis that as a result of central nervous system injury, the brain’s neurons couple together electrically, locking into a neonatal developmental state. He documented the potential avenues for altering that condition.

In the first case, patients with schizophrenia experience a massive increase in rapid eye movement (REM) sleep and hypervigilance. REM sleep normally decreases drastically from birth (50 percent of sleep time) until after puberty (15 percent of sleep time). Garcia-Rill believes that this decrease is disrupted in schizophrenia through an increase in electrical coupling of brain cells controlling REM sleep and arousal, leading to lifelong increases in excitability. This would lead to excessive arousal and overactive responses to sensory inputs, as well as episodes of REM sleep (dreaming) while awake, that is, hallucinations.

Garcia-Rill, who has led spinal cord injury research at UAMS since 1981, is also studying the mechanisms behind a similar increase in electrical coupling after spinal cord injury.  Such excessive coupling could account for such symptoms as hyperreflexia and spasticity. One way to induce the abnormal electrical coupling could be through an increase in the gap junctions – the connecting channels between neurons that mediate electrical communication.

In a patient unable to walk from a spinal cord injury, Garcia-Rill examined both the potential for restoring mobility and a method to combat other side effects to the injury. In a patient in Arizona, he previously developed an epidural device that used electrical stimulation to produce locomotion – not unlike the electrical impulses that cause an infant to move its legs, he said.

Common side effects of spinal cord injuries, in addition to uncontrolled muscle reflexes and spasms, include muscle atrophy. In order for patients to be ready to regain mobility, they must have some muscle mass and not suffer from the reflex problems or spasms that can affect balance.

This led Garcia-Rill and his team to develop the motorized bicycle exercise trainer. The trainer allows the patient to exercise their legs while seated in a wheelchair.

In a clinical test of the trainer, a patient used the trainer an hour a day, five days a week. After eight to 10 weeks, reflexes began to normalize and remained normal. The exercise is thought to electrically uncouple spinal cord cells by providing cyclic movement. After 13 weeks, use of the trainer was stopped and within two or three weeks, the patient’s reflexes had again become hyperactive.  This suggests that electrical coupling had returned.  Animal studies have shown that long-term use of the device may increase muscle mass as well.

In addition to those with spinal cord injuries, Garcia-Rill said he hopes to extend the benefits of the trainer to patients with exaggerated reflexes or muscle spasms as a result of stroke, cerebral palsy and multiple sclerosis.

Current and future research, funded in part by a $7.5 million grant from the National Center for Research Resources at the National Institutes of Health, is intended to determine the minimum level of trainer therapy necessary to eliminate the reflex problems and spasms.

 This award established a Center of Biomedical Research Excellence called the Center for Translational Neuroscience (link), which is intended to bring basic science findings to the bedside.  Aside from psychiatric and sleep disorders and spinal cord injury, work at the CTN includes research on tinnitus and vertigo, chronic low back pain, long-term effects of neonatal pain and pediatric traumatic brain injury, irritable bowel syndrome, spatial neglect due to stroke, contributions by depression to cardiovascular diseases, and developmental regulation.

Links on This Page

Edgar Garcia-Rill faculty listing: http://www.uams.edu/neuroscience_cellbiology/faculty/details.asp?id=48

UAMS Center for Translational Neuroscience:http:// www.uams.edu/ctn

Research at UAMS on Spinal Cord Stimulation Helps Paralyzed Man Walk: http://www.uams.edu/today/2002/020702/GarciaRill.htm

UAMS Enlists Arkansas Company to Build, Market New Bicycle Exercise Trainer for Spine Injury Patients: http://www.uams.edu/update/absolutenm/templates/news_release_liz.asp?articleid=3244&zoneid=86

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