Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein linked to brain cell scarring after injury

04.06.2003


A new study links a protein discovered a few years ago at the University of North Carolina at Chapel Hill with formation of scar tissue that occurs after injury to nerve cells in the brain or spinal cord.


Image of palladin



Such scarring apparently blocks neurons of the central nervous system from recovering after traumatic injury - inhibiting their axon filaments from regenerating and ferrying nerve impulses elsewhere, to other neurons and tissue, including muscle. Loss of nerve cell function and paralysis can result.

The findings, published online today (June 4) in the journal Molecular and Cellular Neuroscience, add new knowledge to a long-standing issue in neuroscience: why do nerve cells in the peripheral nervous system grow back after an injury such as a skin cut, but cells in the brain or spinal cord do not.


"One school of thought has it that there’s something fundamentally different in the neurons of the central nervous system versus the peripheral nervous system. This is likely not to be a major factor," said Dr. Carol A. Otey, assistant professor of cell and molecular physiology at UNC School of Medicine and the study’s senior author. "The second school of thought is that there are chemical changes that occur in an area of injury that are specific to the brain and spinal cord, changes that repel injured neurons from being able to re-extend their axons. And this is now known to be true."

Added Otey: "Also thought to be true is that a physical barrier forms to prevent axon regeneration. And that’s what we’re most interested in, this barrier that’s called the glial scar." When neurons are cut, star-shaped glial cells called astrocytes migrate to the area and weave together to form a glial scar. (Glia are cells that help provide support for neuronal functioning.)

"If the neuron has survived and tries to re-extend its axon, it can’t go through this barrier," Otey said. "The question is, what occurs at the molecular level that’s allowing these astrocytes to behave this way, to move towards the lesion, to change their shape and form a barrier?"

Enter palladin, the protein Otey and her colleagues identified at UNC in 2000.

Named after the 16th century architect, Andrea Palladio, the protein appears to be involved in the architecture of cells, playing a key role in determining cell shape and allowing cells to move.

"We had seen palladin expression correlate with motility in other cell types. So we began by asking if palladin is found in adult mature astrocytes. And it isn’t," said Otey.

But, in the new research, Otey, along with lead author and instructor in cell and molecular physiology Dr. Malika Boukhelifa and others, found that palladin levels increase, are "upregulated," following traumatic injury to the central nervous system.

"We asked this first in tissue culture model, where we had a monolayer of cultured astrocytes. And we could just very easily scrape the monolayer to mimic injury, fix the cells at different time points and check for protein expression," Otey said. Fluorescence microscopy was used to visualize the expression of the protein.

"Palladin gets upregulated rapidly," she said. "You specifically can see it at the tips of the processes pointing into the wound. Using staining techniques, you can see this upregulation at three hours after injury. By six hours after injury, the processes have flattened out and are trying to fill the wound and the whole area now is positive for palladin."

In collaboration with the laboratory of neuroscientist Dr. Juli Valtschanoff, assistant professor of cell and developmental biology, the researchers extended their tissue culture palladin investigations to an animal model, the adult rat. A tiny lesion was made in the animals’ brain with a glass needle and time points after injury were recorded.

The researchers then used fluorescence immunostaining and microscopy to examine the lesion area for palladin expression.

"Just a few hours after a lesion there are these brightly palladin-positive astrocytes close to the lesion, with more appearing at later times," Otey said. "And this is quite persistent. At seven days after injury, there’s this beautiful zone of high levels of palladin expression right around the injury." Thus, according to Otey, the above findings show rapid and persistent palladin expression in cells close to a lesion, in cells that are known to change their shape and to move.

"Now it became important to ask if palladin expression is what causes cells to change their shape?" This was addressed in tissue culture experiments. Using gene transfer methods, astrocytes were "transfected" either with palladin and green fluorescent protein (GFP) or with GFP alone. Cells treated with palladin and GFP lost their stellate, or star-like, shape and became polygonal, thickened and flattened. Cells transfected with GFP alone did not. In addition, palladin-transfected cells also displayed signs of structural changes previously associated with injury and shape change. "So it would appear that palladin is controlling astrocyte cell shape," Otey said.

Might the findings suggest a possible novel therapeutic avenue for central nervous system cell regeneration after injury - whether it be stroke, traumatic injury or repeated epilepsy seizures?

"If palladin upregulation is allowing the astrocytes to form the glial scar, then one approach to enhancing recovery to injured CNS nerves might be to prevent that upregulation," Otey said.

Still, the researcher and her co-authors caution that more work is needed. Experiments now underway are aimed at designing a "knock-out" animal model in which astrocytes cannot express the protein after injury. The researchers will then be able to determine if glial scar formation is attenuated and if doing so will enhance injury recovery.

"It’s likely that in the end we’ll find out it’s more complicated than it is in cell culture," Otey said. "We may learn that the glial scar may be necessary, as it’s unlikely that this structure had evolved simply to cause paralysis.

"It may be necessary to allow the glial scar to form up to a point, then attenuate formation of the scar. It probably serves some function to isolate the area of injury, maybe to prevent an inflammation response. We don’t know. It will be interesting to see, first of all, if it’s sufficient to allow regrowth of axons by preventing the glial scar, or will doing so generate other problems we haven’t anticipated? Indeed, it will be interesting to do these experiments.

Along with Otey, Boukhelifa and Valtschanoff, other co-authors were a visiting scientist from South Korea, Dr. Se-Jin Hwang, Dr. Aldo Rustioni of cell and developmental biology, and Dr. Rick B. Meeker of neurology. The study researchers are members of the UNC Neuroscience Center.


Support for the research came from the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health.

By LESLIE H. LANG
UNC School of Medicine

Note: Contact Otey at (919) 966-0273 or carol_otey@med.unc

L.H. Lang | EurekAlert!
Further information:
http://www.med.unc.edu/

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>