The brain and spinal cord of mammals are chock-full of molecules on a mission to thwart regrowth.
That’s been bad news for stroke and spinal cord injury victims — and in the era of the Iraq war, also for large numbers of soldiers with traumatic brain injury, being called the signature injury of this war because of the enemy’s use of explosive devices or IEDs, improvised explosive devices.
But several recent papers show possible new avenues towards coaxing adult nerve cells to regenerate.
Macrophages are immune system cells that play an important role in the initial cleanup stages after an injury. But if they hang around too long, macrophages can compromise tissue repair by promoting inflammation. In the March 1, 2007 issue of Neuron, researchers from McGill University (Montreal), Stanford University (Stanford, California), and Genentech (South San Francisco) report on factors that encourage macrophages to move out once their mission is accomplished.
The researchers concentrated on Nogo receptors, which are involved in neural growth. They induced damage in the sciatic nerve in the thigh of rats and mice and analyzed the role of the Nogo receptor NgR1 during repair.
Macrophages expressed NgR1 on their surface once they arrived at the injury site and began their cleanup, removing debris of the old myelin sheath. As the healing nerve began to form a new myelin sheath, though, the receptor not only caused a reduction in the macrophages’ binding to myelin, but also an outright repulsion from the forming myelin.
In fact, when the researchers created nerve injury such that new myelin would not be formed, the macrophages continued to lurk around the injury site.
The sciatic nerve, which the scientists used in their studies, is part of the peripheral nervous system, which is able to regenerate itself much better than are the brain and spinal cord. But because the receptors they studied were on macrophages and also are expressed after injury to the brain or spinal cord, the authors believe the same mechanisms may operate after central nervous system injury.
One of the major culprits inhibiting neural regrowth is the family of chondroitin sulfate proteoglycans, and researchers — including those from Acorda Therapeutics (Hawthorne, New York) — are working on using chondoitinases, enzymes that can chew up chondroitin sulfate proteoglycans, to improve repair after injury.
Using a transgenic approach, researchers from Yale University (New Haven, Connecticut) showed, in a paper published in the Feb. 28, 2007, issue of the Journal of Neuroscience, that delivering chondroitinase improved axonal regrowth after injury, but did not improve motor function. It did, however, improve sensory function after experimentally induced injury. The researchers conclude that chondroitin sulfate proteoglycans “appear to function in a spatially distinct role from myelin inhibitors, implying that combination-based therapy will be especially advantageous for CNS injuries.”
Finally, in a study published in the Feb. 21, 2007 issue of the Journal of Neuroscience, researchers from the University of Calgary (Calgary, Alberta), investigate the opposite phenomenon: an enhanced repair capacity for neuronal repair found in mammals during pregnancy.
The scientists investigated the molecular mechanisms underlying the remission from multiple sclerosis — an autoimune disorder that attacks the myelin sheath — that some women undergo during pregnancy. They found that pregnant mice have a greater ability to form new myelin in response to lesions than nonpregnant controls, and that the hormone prolactin regulates oligodendrocyte precursor proliferation and mimicked the effects of pregnancy when administered to nonpregnant mice, suggesting that prolactin or an analogue might be a possible therapeutic strategy for multiple sclerosis.