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As I descended the stairs to Columbia's new human brain bank underneath the ground level of Babies Hospital, I envisioned passing through a vault and seeing a huge, sparkling white room with rows of shelves holding brains in clear glass jars. Instead, I found a windowless suite of five rooms with beige concrete walls and three large freezers hooked up to some serious surge protectors.

But behind the mundane decor, exciting changes in brain banking methods are being introduced and tested in the small facility. Brain banking today goes beyond stashing a few cerebral hemispheres in a minus 80 degree Celsius freezer and shipping bits to interested researchers. The director of the Columbia brain bank, Dr. Jean Paul Vonsattel, professor of pathology, has brought new methods of standardizing tissue collection and storage to the bank. In the future, his new system may link brain banks nationwide, creating uniform banking techniques to foster reproducible research results.

Is cutting a human brain in half, freezing it, and gouging out chunks, as pictured above, any way to treat the seat of our intelligence? No, but that's how brains used to be processed in brain banks. New brain banking techniques, being introduced and developed at Columbia's invigorated brain bank, should improve the quality of samples used for research.
Brain banks in this country collect brains from donors with neurodegenerative diseases and brain tumors and distribute tissue to researchers trying to understand causes of disease, which cells are affected, and how brain changes relate to the clinical stages of the patients. Successful research, though, depends on treating donations well, as Dr. Vonsattel told me he discovered when he began studying Huntington's disease at the Harvard brain bank at McLean Hospital in the early 1980s.

At the time, the bank stored half brains, which were frozen en bloc, in the freezer, and operators partially thawed the tissue whenever someone needed a sample. But freezing and thawing the tissue took its toll on the brain's architecture and quality.

Dr. Vonsattel removed a frozen half brain from the freezer to illustrate his point. The brain, missing a chunk from its frontal lobe, had the color of frozen hamburger, complete with some freezer burn on its surface. The freeze-thaw cycle, he says, eventually destroys cell structure, so he couldn't distinguish between a neuron and a glial cell when he examined samples microscopically. To improve resolution, Dr. Vonsattel says brain banks changed how they process deposits.

"Now, when a brain arrives, we dissect it into 16 coronal slices, subdivide them into smaller blocks, and place each into liquid nitrogen" says Dr. Vonsattel, who is on call to process brains whenever they come. Each of the then total 18 blocks maintains the integrity of important brain regions, such as the superior frontal cortex, the anterior thalamus, and the cerebellum, to name a few. The samples are wrapped in cellophane packets and kept at minus 80 degrees Celsius. After he established the sectional banking method at McLean, Dr. Vonsattel found Huntington's disease first affects portions of the caudate nucleus.

At Columbia since February 2001, Dr. Vonsattel; his postdoctoral researcher, Dr. Christian Keller; and Steven Chin, associate director of the bank, with the support of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, instituted the 18-block system and reorganized the bank's storage system to maximize the limited freezer shelf space, a problem for all brain bankers.

The new system assigns unique coordinates to sample-sized spaces in the freezer, stamps an identifying barcode onto each packet, and keeps track of each sample's location in a computer database. The system saves space and protects samples by limiting the time the freezer door is open. "Before, we weren't always sure of sample's location and spent a lot of time rummaging through the freezer," Dr. Vonsattel says. "Now we find the sample's coordinates in the database, open the door, use a barcode reader to ensure we have the right packet, and remove it."

The bank's new Web site (http://www.nybb.hs.columbia.edu/), which went online in late November, now allows brain researchers to precisely select the samples on which they might want to do immunohistochemistry, histology and cytoskeletal analyses, or mRNA studies. The Web site offers a choice of samples based on patient diagnosis, age, gender, and brain section. Researchers also can obtain the same section from a different brain if they want to repeat an experiment in the future. Any U.S. researcher with an appropriate grant can request free tissue samples but Columbia investigators get priority.

The Columbia brain bank mostly collects brains with neurodegenerative diseases, such as Alzheimer's, Huntington's and Parkinson's diseases, but also has "healthy" brains to serve as controls. The bank also contains brains from patients with schizophrenia, which to date hasn't been linked to any cellular degeneration. Dr. Vonsattel is seeking more donations of healthy and diseased brains for the bank.

The bank has been fully operational during the reorganization, but Dr. Vonsattel still is entering data from some paper-based records into the system and is integrating more information into the database about the extent of pathological changes in any given block of tissue. When the bank makes these changes, Dr. Vonsattel plans to continue his study of the early affected region in Huntington's disease and find more details about disease progression.

Dr. Vonsattel hopes to get National Institutes of Health funding for the bank to expand and introduce the bar-coding system to the other 50 or so brain banks in the country, most of which have adopted the 18-block dissection method. "The Columbia brain bank now," he says, "is like preliminary data for how a larger network of banks can work together."

The New York Brain Bank at Columbia is supported by the Hereditary Disease Foundation.


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