Video: Cerebral cortex histology

Oh, the mysteries of the brain. Although it accounts for just two percent of our total body weight, the brain is arguably the most complex organ of the body responsible for functions such as movement, memory, learning - well, everything really. But in this tutorial, we're not looking at the whole brain. We're actually zooming in onto a thin three-to-four-millimeter layer of brain tissue which is responsible for processing most of the higher functions of the brain. We are, of course, talking about the cerebral cortex.

Let's zoom right in and see what it's all about - as we take a quick exploration of the histology of the cerebral cortex.

So before you start hyperventilating about the thoughts of learning more neuroanatomy, the first thing I want to do is diffuse any preconceptions you might have going into this topic. While it is true that neuroanatomy is probably the most complex topic an anatomy student has to tackle in their studies; however, for your histology exams, it is perhaps one of the easiest topics you will encounter.

So you must be wondering what exactly you'll be learning today. We will start with a recap of some very basic anatomy of the brain, followed by a quick discussion on the inner composition of the brain and a reminder of the structure or parts of a typical neuron. We will then jump into the histology of the cerebral cortex starting with the pia mater that covers the brain. We will then take a comparative look between the gray matter of the cerebral cortex with the white matter located a little deeper. We'll then look at the types of cells found in the cerebral cortex namely neurons and glial cells. After that, we will, as always, finish up with some clinical notes.

But before we jump into the histology of the cerebral cortex, let's have a quick refresher on the gross anatomy of the brain.

So if we look at the brain from a lateral view, there are a few major parts we can identify. We have the brainstem, which is the connection between the brain and the spinal cord; the cerebellum, which plays a major role in motor control as well as some cognitive functions; and finally, we have the cerebrum - the largest part of the brain - responsible for higher functions and the focus of today's tutorial.

If we switch to a coronal view, we can see the internal structure of the brain. Here we can clearly identify two distinct areas. We know the outer layer appears somewhat darker and is known as the gray matter whereas much of the deeper tissue is lighter and is therefore known as the white matter. To understand why this is, let's take a quick look at the structure of a neuron.

As you may already know, there are several different types of neurons, or nerve cells, all of which present variations in their shape and form. That being said, let's take a quick look at a classic representation of a neuron to remind ourselves of the basic makeup of this type of cell.

Neuronal cells are eukaryotic cells - the same as the ones that make up the rest of your body, but their primary unique feature is their extensive network of branch-like projections of the plasma membrane. There is a variable number of usually shorter extensions called dendrites which extends towards the cell body which is the main hub of the neuron.

The cell body usually then gives off a single long projection, which is called an axon, which transmits information away from the cell body. Often the axon of a neuron presents a discontinuous sleeve of fatty tissue known as a myelin sheath and allows faster signal transmission in axons. Due to their pale appearance, areas of cerebral cortex which have a high concentration of myelinated axons is called the white matter. Gray matter, by contrast, mostly consists of neuron cell bodies as well as non-myelinated axons, blood vessels, and supporting glial cells which gives it its darker appearance.

Okay, we're now ready to take a look at what we're here for - the cerebral cortex histology.

Let's take a look at this slide of cerebral cortex tissue and some of the obvious features visible on this section seen even under low magnification. The first thing we can see is that the outer border of our section is not straight. Instead, it shows off the typical pattern of sulci and gyri seen in the cerebral cortex.

While we're talking about these sulci and gyri, it's a good time to mention the layer closely following the contours of the cerebral cortex. I'm, of course, talking about the pia mater. The pia mater is a very fine layer of fibrous connective tissue lined with a simple epithelial layer composed of pial cells which protects the surface of the gray matter. This is the innermost of the meninges covering the brain. Just to remind you, the other two layers are the arachnoid mater and the dura mater; however, neither of these are present in our section.

Now what would a histology tutorial be if we didn't take a moment to mention the stain used on our section here which gives it its color, and this particular section, as you might have guessed, has been stained using the classic haematoxylin and eosin or H&E stain. This staining technique causes basophilic or base-liking structures of the cell like DNA, which we know stands for deoxyribonucleic acid, stain bluish or purple. As they react with the eosin component of the stain, they are also known as eosinophilic structures; however, in the case of nervous tissue, this is not always the case, which we will see later.

On the other hand, acidophilic or acid-liking components of the cell like cytoplasmic proteins and organelles are counterstained with haematoxylin causing them to appear in varying shades of pink. This helps to identify nuclei from their surrounding cytoplasm in a histological section.

So let's talk more specifically now about the makeup of the gray matter in our histological section. As we've already established, gray matter consists mostly of cell bodies of neurons in addition to unmyelinated axons which carry signals away from the cell body. We also have a dense population of supporting glial cells which we will look at more closely in a few moments. And, finally, we have blood vessels which nourish the tissue with oxygen and remove carbon dioxide just like anywhere else in the body. The many dark-staining nuclei of all these cells give the gray matter an overall deep magenta color when stained.

The dense meshwork of interweaving axons and dendrites of neurons and cytoplasmic extensions of glial cells in which the neuron cell bodies are embedded is known as neuropil. The axons from the cell bodies in the gray matter project from the cerebral cortex into the white matter which is stained lighter pink in this section due to sparser staining of the cell nuclei. The white matter connects areas of the brain to each other and to other parts of the body via what's known as tracts which are mostly formed of myelinated axons in addition to supporting glial cells and blood vessels. As the gray matter forms in the cerebral cortex, the white matter is sometimes known as the cerebral medulla.

So the reason why studying histology of the cerebral cortex is relatively easy for anatomy students is because regardless of where we're looking in the central nervous system - be it the brain or the spinal cord - we will only find two primary types of cells in a tissue section. The first of these, of course, is neurons or nerve cells, which we've already talked about. The second type of cell in the CNS are glial cells, also known as neuroglia. These maintain the tissue and function of the brain and are about ten times more common than neurons.

So here we are looking at a high magnification of the gray matter now where we will begin by first taking a look at some neurons. You can easily identify them due to the fact that they're much larger than the surrounding glial cells and sometimes display cytoplasmic extensions which are large dendrites or axons.

Now since this section has been stained with H&E, we would expect to see the nuclei to all appear blue or dark purple in appearance, right? But you can see here that many of the nuclei appear red in color. Why is this, you ask. Well, these are known as red or acidophilic neurons and are indicative of nerve cells which have become damaged due to hypoxia or the absence of blood supply. In such conditions, we can see acute shrinkage and reddening of the cytoplasm while the nucleus becomes shrivelled and hyperchromatic. All of these attributes are representative of cell death, also known as apoptosis. This is commonly seen in prepared sections of brain tissue so it's important to know this if you're an up-and-coming pathologist.

The gray matter is arranged in layers or laminae of which there are six in total. Depending on the laminae in question, the neuron cell bodies appear different as there are six different types of neuron found here. With this type of stain and magnification, it is challenging to tell one type of neuron from another; however, there is one type which is relatively easy to isolate, and that is these neurons here which are known as pyramidal cells due to their triangular appearance.

If we look at them in our histological section, they are easily distinguishable and bear a large apical dendrite pointing towards the outer surface of the cortex and some smaller basal dendrites which are not as easy to identify in histological sections.

As we mentioned earlier, dispersed amongst the neurons of the cerebral cortex are glial cells, also known as neuroglia. These are much smaller than neurons, however, are much more common than them. Unlike neurons, glial cells do not conduct electrical signals but rather support and protect neurons within nervous tissue. They do this by providing physical support to neurons in addition to protecting them by means of maintaining the blood-brain barrier and immune defense.

The word glia is derived from the Greek word for glue which reflects these cells' function to support and hold the neuronal cells together. All in all, there are six types of glial cells - oligodendrocytes, astrocytes, microglia, ependymal cells, Schwann cells, and satellite cells - however, only four of these are found in the central nervous system. These are oligodendrocytes, astrocytes, microglia, and ependymal cells. We won't be talking about ependymal cells today as they are only found along the ventricles of the brain which is not in our section.

Oligodendrocytes are the most common type of glial cell in the CNS and are responsible for insulating the sections of the axon length, which is known as myelination. Unlike Schwann cells which myelinate an axon section of one neuron only, oligodendrocytes have several extensions which myelinate axons belonging to a number of neurons. In a histological section, these are relatively easy to identify and, of course, most plentiful in the white matter of the brain. They have a small round nucleus surrounded by a pale halo.

Moving back to a section of gray matter now, let's now look at another type of glial cell known as astrocytes. These can look quite similar to oligodendrocytes in section; however, whereas oligodendrocytes were more common in white matter, astrocytes are much easier to spot in gray matter. The easiest way to find them is to look for a blood vessel and neuron located close together and then look for smaller cells in between. These are more than likely to be astrocytes as they function to physically support neurons in addition to contributing to the formation of the blood-brain barrier around cortical blood vessels. They do this by a cytoplasmic extension known as end feet which create a barrier around cortical vessels forming what's known as glia limitans or glial-limiting membrane.

The last type of glial cells, which we can sometimes identify in histological sections like this are microglia. These cells are not as easy to identify in routine stains as they have a very small nucleus and are more difficult to isolate. These cells here are likely to be microglia as they have particular small nuclei compared to adjacent cells. Sometimes, they may appear to have an oblong or fusiform-shaped nucleus.

Microglia are the macrophage-like cells of the central nervous system and are known to clear up cellular debris and dead neurons from nervous tissue by means of phagocytosis. They are also now known to play a key role in regulating pathways of CNS inflammation.

In this section, we can also see some small microscopic blood vessels that are supplying the gray matter. Although it only accounts for about two percent of our body weight, the brain consumes about twenty percent of the heart's output due to the extraordinary amount of energy needed to maintain the cellular processes which occur here. To this end, it should come as no surprise that the cerebral cortex is extremely well vascularized with plenty of capillaries visible.

As with all capillaries of the body, these are formed by endothelial cells and red blood cells are often seen within the vessel lumen itself. The space around the capillaries is known as the perivascular space, which is an important space to know about for several pathological processes in the brain.

Okay, we're done with the histology part of this short and sweet tutorial, but before we finish up, let's take a look at some clinical notes.

Let's talk a bit about multiple sclerosis or MS. If you're familiar with this disease, chances are that you're thinking MS affects white matter and you are not wrong. MS famously has been linked with destruction of myelin on axons creating a wide array of neurological symptoms. But in the last two decades or so, it has also been shown to affect gray matter. It is believed that MS acts by causing the immune system to attack the central nervous system. It is suspected that this is linked to genetic predisposition and environmental factors.

It causes atrophy or degeneration of tissue which leads to a reduced volume of the gray matter both in the cortical and deep gray matter structures. This may manifest as fatigue, cognitive changes, and memory loss depending on the areas affected.

So how is it helpful for us to know that MS also affects the gray matter?

Gray matter atrophy has been shown to occur even before any lesions in the white matter. That means MS could be diagnosed sooner and understanding its mechanism better can help us predict its progression. Unfortunately, things are never that easy. Gray-matter lesions can only be picked up using a specialized MRI machine which is also the reason scientists only began studying them in the last couple of decades. At the moment, the aim is to carry out longitudinal studies where scans obtained early in the disease progression can be related to its patterns.

Before we finish up, let's take a quick look at what we learned today.

Today, we looked at an H&E stained slide of the cerebral cortex. First up, we identified the structures visible at lower magnification - the sulci and the gyri. We then saw the fibrous pia mater before moving on to the gray matter forming the cerebral cortex. Here we identified neuron cell bodies and observed how in deeper layers of the cortex they had a triangular appearance and were, therefore, called the pyramidal neurons. We also saw plentiful glial or supporting cells and capillaries. Finally, we took a quick look at the white matter.

Okay, that's it for this quick tutorial on the histology of the cerebral cortex.

I hope you enjoyed watching it as much as we enjoyed making it. Happy studying!