I feel terribly privileged when I'm handling human brains. This tissue is something bequested to us for research purposes and it's an honour to be able to handle the tissue and meet that bequest. My name's Steve Gentleman. I'm the Professor of Neuropathology at Imperial College, London and one of my jobs is to carry out the diagnostic assessment of the brains that come in to our tissue bank. The first thing you do when you get the brain is to examine the external features of the brain to see if there's any clue there as to what might've gone on. So you look at the surface of the brain, the membranes that cover the brain, is there any evidence of any infection? We then look at the patterns on the surface of the brain at the folding to see if that's normal and whether there's any shrinkage or atrophy in any particular areas. Also, feel the brain to see if there's any softenings, because if there is a soft area that may indicate there was a stroke in that area.
Then look at the blood vessels at the base of the brain and they will give us some clues as to lifestyle factors that may have been involved. They may be atherosclerotic, or hardening of the arteries, due to a high fat diet or smoking or lack of exercise all may contribute to this type of change. When we have a whole brain fixed in formalin, what will do is we will make a cut through the brain stem, which is that part of the brain which is quite small but very important in carrying out all those everyday functions that we all rely on without thinking about too much. We separate the brain stem and the cerebellum from the rest of the brain. In order to carry out the neuropathological examination in a reproducible fashion, we have to cut up the brain in a fairly stereotypical way.
So we use a single point for our first cut. We have a landmark called the mammillary body – it's a part of the brain involved in housekeeping functions, and we use that as our guide for the first cut using a rather large bread knife, if you like – that's what it looks like. We then slice the brain up in to coronal sections and then space those out so that we can have a look through the whole extent of the brain to look for any pathology, and then to take some representative blocks so that we can follow up and look down the microscope at what's going on.
And in this way we can build up a diagnostic report of what the problem was with that particular patient. And this is very important because the tissue then goes out to researchers and they need to know exactly what was going on. We cut the sections using a guide because there are some parts of the brain that we need to look at which are quite small, so we have to accurately make a half-centimetre slice.
When all the slices are laid out in a logical fashion you can inspect each slice individually working from the front to the back of the brain, just checking that all the structures are as you would expect them to be, looking for any signs of change, whether it be in multiple sclerosis, for example, there may be changes in the colour of parts of the brain. We then have to sample 20 specific anatomical areas to allow us to take them away to be stained and look at them down the microscope, to try and work out which pathologies are there, because it's not always just one pathology. We have to make sure if there are multiple pathologies, that we write that down, and again, it's very important for the researcher, they need to know everything that's gone on in the brain. The samples we take are put into small plastic cassettes and these are then embedded in paraffin wax and the reason we do this is to get very, very thin slices to look at under the microscope we need to mount the tissue into something that can be cut. So those are cut at about six microns, which is very, very thin and allows us to look at the tissue.
I've been looking at brains for 25 years now and I have probably examined over a thousand. Every brain is individual. When I first pick up the brain, what I'm looking at is the external features and, if you like, the convolutions of the brain are a little bit like a fingerprint – they are unique to the individual. Obviously they have a very similar general structure, but there are subtleties, we're all slightly different in our development so no two brains are the same, and indeed that applies to the pathology as well. Parkinson's disease is a very well-described disease, but in fact the pathology you see in the brains of people who've had Parkinson's disease is very individual.
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