09 March 2009

Rebuilding a Damaged Brain and More

After strokes and other types of brain damage, entire areas of brain can die and be replaced by fluid filled cavities or depressions. Scientists at Kings College London are experimenting with a biodegradable polymer matrix that may someday re-build the damaged brain after strokes, abscesses, and other types of brain damage.
Scientists say that the key to the advance, published today in the journal Biomaterials, is the use of a biodegradable polymer called PLGA, which ensures that the stem cells remain in the area of stroke damage and establish connections with surrounding brain tissue. By reducing the number of stray stem cells, the system is likely to be safer as well as more effective than other methods, the researchers add.

...The researchers injected particles of the PLGA polymer loaded with neural stem cells directly into the stroke cavities. Once inside the brain, the particles link up to form complex scaffolds. Modo's team used MRI scans to pinpoint where the stem-cell injections were needed and to monitor the development of new brain tissue. "Over a few days we can see cells migrating along the scaffold particles and forming a primitive brain tissue that interacts with the host brain," says Modo. "Gradually, the particles biodegrade, leaving more gaps and conduits for tissue, fibers, and blood vessels to move into." The next step, he says, will be to add the growth factor VEGF, which should encourage blood vessels to enter the new tissue and speed its development into mature tissue.

...The key to the advance was the ability of the new polymer to encourage the growth and differentiation of the neural stem cells at three different scales, says Modo's colleague Kevin Shakesheff, a tissue engineer at Nottingham University. "At the large scale, it enables the void formed by the injury to get new blood vessels very quickly, which is vital if the new tissue is to survive. At the cellular level, the scaffold surface allows stem-cell receptors to attach to it. And at the molecular level, it will allow cells to mix with the right growth factors." _TechnologyReview
Another fascinating area of brain research involves the use of ultra-short electrical pulses to affect nanopores in the nuclear membranes of neurons, while leaving the nanopores of the cell membrane intact. This specificity appears to have interesting effects on the behaviour of neurons individually and as a group.
When an electric field is applied to a cell, a charge starts to build up on the cell membranes. After a few microseconds, the charge is so high that holes (or "pores") start to form in the cell wall, an effect called electroporation. This allows material (in particular calcium ions) to pass through, affecting the function of the cell. With shorter pulses there is not enough time to affect the cell. But electroporation can affect the structures within the cell such as the nucleus, known as organelles.

"Because the organelles are much smaller than the cell itself... they reach their maximum charge much more quickly," Center founder Karl H. Schoenbach explains in an article. " Ending the pulse after the organelles are charged up, within a few hundred nanoseconds but before large pores appear in the cell’s own membrane, lets you focus the electric field’s effects on the organelles, such as the nucleus, while leaving the cell membrane relatively untouched. That, in turn, lets you do the complex and varied things medical science is interested in, such as killing tumor cells or triggering an immune system response."

So on the one hand ultra-short pulses can be used to selectively destroy cancerous cells. But they can also produce much more effective stunning effects.

A paper from the Center on Neuromuscular disruption with ultrashort electrical pulses compares 450-nanosecond pulses with multi-microsecond Taser pulses and found that the shorter pulses were more effective for suppressing voluntary movement, and used less energy. Another study found that even shorter, 60-nanosecond pulses could stun rats.

But the most significant is a paper which found that it was possible to incapacitate cells for a prolonged period -- "our study provides experimental evidence that even a single 60-ns pulse at 12 kV/cm can cause a profound and long-lasting (minutes) reduction of the cell membrane resistance (Rm), accompanied by the loss of the membrane potential." _Wired
I understand if a readers eyes fog up while reading fine print in italics dealing with scientific topics, particularly late at night when they really should be in bed asleep. But it might be worth one's time to contemplate the implications of research on ultra-short electrical pulses on neurons individually and in aggregate.

I will come back to both of these topics in the future.

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