REHOVOT, ISRAEL -- September 17, 1996...Why is it that humans and other mammals are left permanently paralyzed or otherwise handicapped by injuries to the central nervous system, while fish and other "lower" life forms can repair such injuries and resume normal lives?
A study led by Prof. Michal Schwartz of the Weizmann Institute of Science, reported in the September issue of The FASEB Journal (the official publication of the Federation of American Societies for Experimental Biology), provides an explanation that links the mammalian inability to repair central nerve damage with evolution -- and offers hope for developing an effective treatment for injuries to the spinal cord and other parts of the central nervous system.
Evolution allowed mammals to have complex brains, capable of acquiring new knowledge throughout a lifetime. But, according to Schwartz, along with this asset came a disadvantage: the brain and the rest of the central nervous system lost their self-healing ability, which exists in lower vertebrates. Schwartz says this loss probably occurred as a result of the critical need to protect the brain from remodeling by the immune system: while immune cells normally help to heal damaged tissue, their access to the brain would disrupt the complex and dynamic neuronal networks that build up during an individual's lifetime.
"There seems to have been an evolutionary trade-off," Schwartz says. "Higher animals protected their central nervous system from invasion by the immune system, but paid the price of forfeiting their ability to regenerate injured nerves. Thus, an evolutionary advantage that protects the healthy brain turns into a disadvantage in the case of injury."
Generally, when tissue damage occurs, immune cells known as macrophages swarm to the injured site, where they remove damaged cells and release substances that promote healing. The central nervous system in mammals is an exception in this regard: when damaged, it is not effectively assisted by the immune system.
Schwartz's team found that this is because the mammalian central nervous system contains an active component that suppresses the macrophages. As a result, relatively few macrophages are recruited to central nervous system injuries, and those that are recruited fail to become "activated" and are ineffective.
"We have shown that the immune system's assistance is just as vital for the repair of the mammalian central nervous system as it is for any other tissue," Schwartz says. "However, because of a suppressive mechanism which seems to have developed in the course of evolution, this assistance does not operate."
The explanation emerged from a series of experiments conducted by a Weizmann Institute Neurobiology Department team that included Orly Lazarov-Spiegler, Adi Ben Zeev-Brann, David Hirschberg and Dr. Vered Lavie, working with Dr. Arieh S. Solomon of the Sheba Medical Center near Tel Aviv.
"Educating" immune cells
The scientists examined whether this obstacle to nerve regeneration could be overcome by using macrophages that had been "educated" by special treatment outside the body. For this purpose, rat macrophages were first isolated and then activated through incubation with injured sciatic nerves, which, as part of the peripheral nervous system, are capable of regeneration. The scientists then transplanted the activated macrophages into injured rat optic nerves, which, as part of the central nervous system, normally do not regenerate.
The pre-activated macrophages induced the optic nerves to regrow.
"Macrophages may be the missing link in the process of wound-healing in the central nervous system," Schwartz says. Transplanting suitably activated macrophages into injured nerves may help overcome the central nervous system,s failure to respond after injury. According to Schwartz, the procedure might eventually be developed into a novel, practical and potent treatment to repair central nervous system injuries, and particularly to restore movement in cases of spinal injury although such a development may still take many years. "This approach would in effect mean turning the evolutionary clock back to the distant past," Schwartz says.
Prof. Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology at the Weizmann Institute. The study was supported in part by the Alan T. Brown Foundation of Nerve Paralysis, and by the donation of Ralph Colton to the Weizmann Institute/University of Michigan scientific exchange program.
The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,400 scientists, students, technicians, and engineers pursue basic research in the quest for knowledge and the enhancement of the human condition. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities.