08 April 2008

Spy Eye Drops for Brain Probing

In experiments on mice, gene probes allowed Harvard University scientists working under the guidance of Dr. Philip Liu to obtain MRI images of gliosis – the proliferation of glia (brain cells that fill the spaces between neurons and strengthen protective, metabolic and transport functions). Gliosis occurs as a result of various brain injuries and diseases. This process leads to the formation of fibrous scars, which occurs in diseases such as Alzheimer's and Parkinson's diseases, as well as being a complication of tumors and brain injuries.

To create a gene probe, scientists attached to the contrast agent used during MRI, superparamagnetic iron oxide nanoparticles (superparamagnetic iron oxide nanoparticles, SPION), a DNA sequence complementary to the matrix RNA of glial fibrillary acidic protein (glial fibrillary acidic protein, GFAP), which is part of glial cells. The resulting probe was tested on animals with a broken blood-brain barrier that regulates the transport of various compounds between blood and brain tissues (the blood-brain barrier ceases to function normally in many neurological disorders, including stroke, multiple sclerosis and viral infections).

In earlier works, the authors injected gene probes directly into the brains of animals. Their latest achievement is the replacement of injections with eye drops. Presumably, nanoparticles penetrate into the brain through the lymphatic vessels of the eyes. In the vascular bed, lymphatic fluid mixes with blood and, in cases of violation of the blood-brain barrier, probes can move from the eyes to the brain.

After instilling eye drops containing nanoparticles into mice, the scientists conducted an MRI scan of the brain of living animals and compared the images obtained with tissue sections (the process of gliosis is visible on the upper pair of images, the brain of a healthy animal is visible on the bottom in the picture and on the slice under a microscope). Such images are a valuable indicator of brain damage and neurological disorders. Regular brain scans can be performed as a monitoring of the patient's condition.

In addition, conducting such tests can improve the effectiveness of treatment of patients with brain disorders and brain injuries. On the one hand, gliosis is a useful mechanism for isolating damaged tissues, on the other hand, it prevents brain regeneration.

Therefore, the detection of gliosis can be considered as a signal for the introduction of inhibitors of this process, which will ensure an increase in the period of tissue regeneration. In addition, modifications of the approach developed by Liu and colleagues can theoretically be used for targeted delivery of drugs to damaged regions of the brain.

Experts believe that in theory the developed concept has a very great potential, but many doubt the specificity of gene probes for gliosis, as well as their effectiveness when administered to people with various pathological conditions. To clarify these issues, the authors still have a lot of work to do.

Article by Christina H. Liu et al. Noninvasive delivery of gene targeting probes to live brains for MRI transcription is published in the April issue of The FASEB Journal.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of TechnologyReview

08.04.2008

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