Donald Stein's Research: Recovery from Traumatic Brain Injury (TBI)
One Doctor's Lonely Quest To Heal Brain Injury
After 40 Years, Skeptics Back Hormone Therapy; Experiments in a Trailer
By THOMAS M. BURTON
September 26, 2007; Page A1
Dr. Stein still wanted to figure out why those brain-injured rats seemed to recover. But he says he concluded that he wouldn't win tenure if he pursued the question.
In 1966, with a wife and young child to support, he left MIT to take a job as a psychology professor and director of the brain-research lab at Clark University in Worcester, Mass.
His growing interest in the possibility of recovery from brain injury put him in a tiny minority. Most neurologists at the time still agreed with Nobel laureate Santiago Ramón y Cajal, who wrote in 1913, "In the adult brain, nervous pathways are fixed and immutable. Everything may die, nothing may be regenerated."
Starting in the late 1960s, Dr. Stein began publishing research that suggested the Nobel winner was wrong.
His lab began methodically studying precisely why some rats stayed smart despite injury. The researchers would place rats in a large vat of water. The rats had to swim to reach a safe platform in a test called a "water maze." Then the scientists surgically damaged the animals' brains to study what happened after injury: Would they still be able to maneuver through the maze? The rats that recovered quickly were all female, although not all of the females recovered.
Dr. Stein considered whether the explanation might be something complex, like molecular or genetic differences between males and females. But investigating that would take much more time and money than seeing if a female hormone might yield some clues. First his team evaluated estrogen, but didn't find a major correlation. Then they tried progesterone -- a female hormone that helps protect fetuses from injury during pregnancy.
In these early experiments, Dr. Stein tested female rats to see if they would recover better or worse at different times during their hormonal cycles that resemble human menstruation. Progesterone levels rise and fall during these cycles, and these early studies did indeed show that female rats that were high in progesterone recovered faster.
Dr. Stein thought he had a big part of the answer to the question that had been vexing him for years. The medical establishment, however, largely shrugged off the results.
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