Monday, December 14, 2009

New Hope for Brain, Spinal Cord Injuries

Deletion of key gene could help nerve fibers regenerate, researchers say


Deleting a gene that suppresses natural growth factors enables regeneration of injured nerve fibers (axons) in mice, a new study shows.

The finding may lead to new treatments for people with brain and spinal cord injuries.

Researchers at Children's Hospital Boston deleted the gene SOCS3 -- an inhibitor of a growth pathway called mTOR -- in the retinal ganglion cells of mice. These cells are in the optic nerve, which carries signals from the eyes to the brain.

Removel of SOCS3 resulted in vigorous growth of injured axons. The greatest improvement was seen after one week, when the researchers also detected signs that the mTOR pathway was re-activated. Axon growth increased even more when the researchers applied a growth factor called ciliary neurotrophic factor (CNTF) directly to the eye of mice in which SOCS3 had been deleted. But CNTF only modestly boosted axon growth in mice that still had SOCS3.

"CNTF and other cytokines [cellular signaling molecules] have been tested for promoting axon regeneration previously, but with no success," study leader Zhigang He, of the F.M. Kirby Neurobiology Center at Children's Hospital Boston, said in a university news release. "Now we know that this is due to the tight negative control of SOCS3. Inhibiting SOCS3, using small molecule compounds or RNA interference, might allow these cytokine growth factors to be functional."

The study appears in the Dec. 10 issue of Neuron.

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Sunday, December 14, 2008

Fat Cells May Restore Spinal Cord Function Post Injury

Mature fat cells helped mice recover from spinal cord injuries, according to a promising new study. They could become a source for cell replacement therapy to treat central nervous system disorders in humans.

Yuki Ohta of the St. Mariana University School of Medicine, Kawasaki, Japan, who led the study, said fat or adipose-derived stem cells have been shown to differentiate into neuronal cells in a test tube setting.

Now, for the first time fat cells have been shown to successfully differentiate into neuronal cells in in-vivo (animal models) tests. The fat cells are grown under culture conditions that result in their becoming de-differentiated fat (DFAT) cells, according to a St Mariana release.

"These cells, called DFAT cells, are plentiful and can be easily obtained from adipose tissue without discomfort and represent autologous (same patient) tissue," said Ohta.

Tests in animal models confirmed that the injected cells survived without the aid of immunosuppression drugs and that the DFAT-grafted animals showed significantly better motor function than controls, said Ohta and colleagues.

"We concluded that DFAT-derived neurotrophic factors contributed to promotion of functional recovery after spinal cord injury (SCI)," said Ohta.

"Transplanting DFAT cells into SCI rats significantly promoted the recovery of their hind limb function."

"These studies demonstrate the ability to obtain stem cells from a patient?s own fat that can help repair injury to the spinal cord," said Paul R. Sanberg, University of South Florida Health, and joint editor-in-chief of Cell Transplantation, which published the report.

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Sunday, July 20, 2008

Stem Cells Identified for Spinal-Cord Repair

A researcher at MIT?s Picower Institute for Learning and Memory has pinpointed stem cells within the spinal cord that, if persuaded to differentiate into more healing cells and fewer scarring cells following an injury, may lead to a new, non-surgical treatment for debilitating spinal-cord injuries.

The work, reported in the July issue of the journal PLoS (Public Library of Science) Biology, is by Konstantinos Meletis, a postdoctoral fellow at the Picower Institute, and colleagues at the Karolinska Institute in Sweden. Their results could lead to drugs that might restore some degree of mobility to the 30,000 people worldwide afflicted each year with spinal-cord injuries.

In a developing embryo, stem cells differentiate into all the specialized tissues of the body. In adults, stem cells act as a repair system, replenishing specialized cells, but also maintaining the normal turnover of regenerative organs such as blood, skin or intestinal tissues.

The tiny number of stem cells in the adult spinal cord proliferate slowly or rarely, and fail to promote regeneration on their own. But recent experiments show that these same cells, grown in the lab and returned to the injury site, can restore some function in paralyzed rodents and primates.

The researchers at MIT and the Karolinska Institute found that neural stem cells in the adult spinal cord are limited to a layer of cube- or column-shaped, cilia-covered cells called ependymal cells. These cells make up the thin membrane lining the inner-brain ventricles and the connecting central column of the spinal cord.

?We have been able to genetically mark this neural stem cell population and then follow their behavior,? Meletis said. ?We find that these cells proliferate upon spinal cord injury, migrate toward the injury site and differentiate over several months.?

The study uncovers the molecular mechanism underlying the tantalizing results of the rodent and primate and goes one step further: By identifying for the first time where this subpopulation of cells is found, they pave a path toward manipulating them with drugs to boost their inborn ability to repair damaged nerve cells.

?The ependymal cells? ability to turn into several different cell types upon injury makes them very interesting from an intervention aspect: Imagine if we could regulate the behavior of this stem cell population to repair damaged nerve cells,? Meletis said.

Upon injury, ependymal cells proliferate and migrate to the injured area, producing a mass of scar-forming cells, plus fewer cells called oligodendrocytes. The oligodendrocytes restore the myelin, or coating, on nerve cells? long, slender, electrical impulse-carrying projections called axons. Myelin is like the layer of plastic insulation on an electrical wire; without it, nerve cells don?t function properly.

?The limited functional recovery typically associated with central nervous system injuries is in part due to the failure of severed axons to regrow and reconnect with their target cells in the peripheral nervous system that extends to our arms, hands, legs and feet,? Meletis said. ?The function of axons that remain intact after injury in humans is often compromised without insulating sheaths of myelin.?

If scientists could genetically manipulate ependymal cells to produce more myelin and less scar tissue after a spinal cord injury, they could potentially avoid or reverse many of the debilitating effects of this type of injury, the researchers said.

Provided by MIT

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Wednesday, April 30, 2008

Decompression Aids Spinal Injury Recovery

Done within 24 hours, the procedure improved neurological outcomes a year later


Surgical decompression of the spinal cord involves the removal of various tissue or bone fragments that are being squeezed and comprising the spinal cord. While commonly done after an injury occurs, the timing of the procedure varies widely.

The study looked at 170 patients with cervical spinal cord injuries, graded as A (most several neurological involvement) to D (least severe), who underwent decompression surgery.

Six months after the surgery, 24 percent of the patients who had the surgery within 24 hours showed two-grade or greater improvement in their condition compared with only 4 percent in the group that had the surgery more than a day later.

"The initial results suggest that decompression within 24 hours of injury may be associated with improved neurological recovery at one-year follow-up. However, further recruitment of patients with long-term follow-up is necessary to validate these promising results," study author Michael Fehlings, head of the Krembil Neuroscience Center at the University Health Network in Toronto, said in a prepared statement.

Fehlings was expected to present the findings in Chicago April 28 at the annual meeting of the American Association of Neurological Surgeons.

Every year, almost 12,000 people in the United States and Canada, mostly young adults, sustain a spinal cord injury. Although surgery, such as decompression, can help, these procedures often do not dramatically improve overall recovery and outcome.

"This is an area of medicine that has not seen tremendous scientific advances, so there remains an urgent need to improve upon current interventions to help restore neurological function in patients with acute (spinal cord injury)," said Fehlings, who is also professor of neurosurgery at the University of Toronto.

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