Wednesday, 11 November 2015

The brain: An essential gift to neuroscience


Have you ever considered donating your brain for research or do you know someone who has? And are you wondering what happens to a donated brain?

The human
brain is difficult to study in living people, therefore much of the research into neurodegenerative diseases such as motor neuron disease (MND), Parkinson’s and Alzheimer's disease relies on studying donated brain tissue - or animal or cell models which can only resemble what happens in living humans. Brain tissue helps us to understand what happens in the brain as a result of disease and is essential to develop new and better treatments.

I can’t stress enough how important it is for us scientists that people help us by donating their brains to research. Sadly, due to lack of awareness, brains from healthy donors which are needed as control tissue are particularly scarce.

Examining brain tissue is a big part of my own research and I’d like to give you some insights into how a donated brain is prepared and used for research:

1. THE CONSERVATION

When a brain is donated to research it needs to be treated immediately; generally, one half of it will be frozen and stored at -80°C, and the other half will be fixed in formalin for at least two weeks, which preserves everything in the brain. These two methods make the brain useful for future investigations, and both of them will conserve the brain for many years.

The conserved brain tissue is stored in a brain bank, a central repository that allows researchers from around the world to request and use tissue for their investigations. For most studies only a very small amount of tissue is needed, so each donated brain can benefit a large number of research studies.

2. THE EXAMINATION

The formalin-fixed brains are then examined by a professional neuropathologist. A neuropathologist is a medical doctor who prepares and examines the donated brains in order to diagnose neurological conditions. Extremely sharp knives are used to slice and dissect the brain in a particular order and to observe certain features which are key in the diagnosis of brain diseases. The brain can then either be classified as healthy, or it can be allocated to a disease group according to the diagnosis.

3. THE WAX EMBEDDING


To take a closer look at the brain under the microscope, brain samples need to be sectioned, i.e. cut into very thin almost transparent slices. As fixed tissue is too soft to be sectioned straight away, we need to harden it to make it easier. To picture this, think of the difference between cutting a chicken breast before and after cooking it: it is way easier to do it afterwards, because it has been hardened! The usual way to harden the brain is by embedding smaller bits of it in a paraffin wax. The tissue will be dehydrated and then immersed in warm paraffin wax. After that, we let the wax harden at room temperature to obtain a solidified brain block. 
 

4. THE SECTIONING

Once the brain tissue is hard, it can be easily sectioned using a specialised machine called “microtome” like the one shown below. 




The microtome cuts 5 micrometre thick slices off the brain block. For you to picture how thin these slices are, 5 micrometres is a half of the width of a cotton fibre. 




These extremely thin sections are then mounted on a transparent glass slide like the ones below.

5. THE STAINING


 

As you can see, the section is colourless just after being cut. This is what almost any kind of tissue will look like after being sectioned this thin. For us to look at anything under the microscope, we need to stain the brain with different dyes which will show specific features that we researchers are interested in. Examples of these features are protein aggregates in MND, or loss of myelin in a variety of neurological diseases. 


On the right is a microscopic picture of a stained brain cortex section. That section has been stained to show the myelin sheaths of the neuronal axons, which appear in brown, forming bundles of fibres. Every single small blue circle is a cell’s nucleus, and blood vessels (which span the brain to supply it) usually appear as big hollow structures. 

Once the brain slides are stained, we can compare healthy brains with those from people who suffered a brain disease, in order to try to find the main characteristics and the possible causes of the disease. 

I hope you found this story of what happens to a person’s brain after the donation very interesting and useful. Most advances in our understanding of brain diseases have come through people who volunteer to take part in research through brain donation programmes.

We scientists are very grateful for these donations as they help us fight some of the most terrible diseases such as Alzheimer's, Parkinson’s and motor neuron disease, and I hope that someday we will find a cure thanks to these donors that will benefit their children and grandchildren so we can give something back.


  
By Alejandro Lorente Pons

I am a PhD student in SITraN and I am investigating brain cells called oligodendrocytes and how they contribute to C9ORF72 MND. You can follow me on Researchgate and on Twitter @ALorentePons. 







 


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