Blood vessels are the "scaffolding" for axonal repair
July 5, 2011 at 11:03am
Researchers at Johns Hopkins have shown how important healthy blood vessels are for the healing of damaged axons and nerves. Blood vessels actually form the scaffolding, or supportive network, upon which axons can regenerate. If the blood vessels are not healthy, the axons can't repair. Healthy blood vessels need an intact endothelium, or lining, in order to communicate with the rest of the body.
This study was conducted with diabetic patients. Biopsies were taken from their thighs, and the sites of healing were studied. This is a different disease process than MS, in that these neuropathies are "peripheral" or involving the limbs, not "central" and involving the brain. Instead of oliogodendrocytes forming around axons, peripheral nerves are covered by Schwann cells. But the process of healing damaged axons might be very important for us to understand in MS research (especially since we are not able to study brain biopsies and axonal regeneration in vivo.)
Here is the press release from Johns Hopkins---
Blood vessels and supporting cells appear to be pivotal partners in repairing nerves ravaged by diabetic neuropathy, and nurturing their partnership with nerve cells might make the difference between success and failure in experimental efforts to regrow damaged nerves, Johns Hopkins researchers report in a new study.
About 20 percent of diabetics experience neuropathy, a painful tingling, burning or numbness in the hands and feet that reflects damage to nerves and sometimes leads to infections and amputation of the toes, fingers, hands or feet over time. Current treatments for diabetic neuropathy focus on relieving symptoms but don’t address the root cause by repairing nerve damage. Previous research has shown that nerve cells’ long extensions, known as axons, regenerate slowly in diabetics, scuttling various experiments to regrow healthy nerves, says study leader Michael Polydefkis, associate professor of neurology at the Johns Hopkins University School of Medicine.
Searching for the reasons behind this slow regeneration, Polydefkis, along with Johns Hopkins assistant professor of neurology Gigi Ebenezer and their colleagues, recruited 10 patients with diabetic neuropathy and 10 healthy people of similar ages and took tiny (3 millimeters) “punch” biopsies from the skin of participants’ thighs. Several months later, they took 4 millimeter biopsies from the same sites to see how the nerves, blood vessels and nerve-supporting cells, called Schwann cells, were growing back into the healing biopsy site.
In both the neuropathy patients and the healthy individuals, results reported in the June issue of Brain showed that the first to grow into the healing skin were blood vessels, followed soon after by Schwann cells and then axons, which appeared to use the blood vessels as scaffolds.
However, the entire process was significantly delayed for the neuropathy patients. Not only was axon regeneration slower compared to that in the healthy patients, as expected, but blood vessel growth rate was also slower, and fewer Schwann cells accompanied the growing axons into the healing skin.
“Our results suggest that regenerative abnormalities associated with diabetes are widespread,” Polydefkis said. “They’re not just affecting nerves; they’re also affecting blood vessel growth and Schwann cell proliferation.”
Additionally, he says, the findings could explain why blood vessel–related problems, such as heart attacks and strokes, often accompany diabetes. Slowed regeneration of damaged blood vessels could contribute to these conditions as well, he says.
Polydefkis says that the findings provide potential new targets for treating neuropathy and vascular problems. By promoting blood vessel and Schwann cell growth, researchers might be able to speed up axon regeneration and successfully repair damaged nerves and blood vessels, potentially combating diabetic neuropathy and vascular complications simultaneously.
Here is the complete abstract:
Impaired neurovascular repair in subjects with diabetes following experimental intracutaneous axotomy
Rich and Veves, using laser Doppler, looked at patients with neuropathy and endothelial function. The endothelium produces nitric oxide in response to acetylcholine. Normal endothelium responses occurred in controls and diabetic patients, but in patients with diabetic neuropathy, endothelial response was impaired..... An impaired response here implies a problem with the vessel wall in neuropathy, Charcot and vascular disease. Endothelial dysfunction in neuropathy can be caused by several things, including insulin resistance, metabolic abnormalities and advanced glycation end products. It results in decreased capillary flow, nerve hypoxia, and then nerve dysfunction.
Endothelial dysfunction seems to have primacy in diabetic neuropathy. Thus, we are moving away from blood sugar as a primary cause into more vascular- and cardiovascular-related causes.
http://www.vasculardiseasemanagement.com/content/an-overview-peripheral-neuropathy-diabetes
I mentioned diabetes as one of the diseases with a connection to endothelial dysfunction in my paper on the endothelium-- diabetes is a vascular disease with neuropathic symptoms. For ideas on how to heal blood vessels and encourage good flow and nitric oxide, check out the Endothelial Health Program.
Blood flow, the endothelium and healthy vessels are important. And as we are learning, perhaps more important than we had imagined.
Joan
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