 Okay. Good day everybody. This is the first part of our video on blood-brain barriers and circumventricular organs. I am Dr. Sanjay Sanyal, Professor and Co-Director of Neuroscience and the camera person is Mr. Mark Lesser. Way back in 1882, Paul Earley injected tripe and blue intravenously in experimental animals. Thereafter, when he dissected the brain, he noticed that there were most areas of the brain that did not get stained with the dye. So obviously, these areas were inside the blood-brain barrier. However, he did notice that there were some areas of the brain which received the stain from the dye. Therefore, he assumed that these structures were outside the blood-brain barrier. That means they do not have a blood-brain barrier. So that brings us to this issue of what is a blood-brain barrier and what is outside the blood-brain barrier. Blood-brain barrier is not something which you can see with our bare eye because it is a microscopic structure. It is a barrier, a microscopic barrier between the blood in the capillaries and the brain substance. So to understand the blood-brain barrier, let us take a quick look at this picture here. If you notice that the central portion is the capillary, a single capillary. The essential component of the blood-brain barrier is the tight junction between the endothelial cells. This tight junction is mediated by special proteins which are known as Claudin and Euclidin proteins and they constitute a very tight lipid bilayer. This is the most important component of the blood-brain barrier. Now, if you look just after that, we see a thin layer of basement membrane which also contributes to the blood-brain barrier. And finally, we have the foot processes of the astrocytes which are known as podocytes and they also substantiate and contribute to the total blood-brain barrier. And therefore, substances cannot easily pass through from the capillaries, from the blood in the capillaries to the brain substance. And as we can see from those small red arrows, they act as a barrier to substances from passing outside. So this is the microstructure of most areas of the brain where there is a blood-brain barrier. In contrast, let us take a look at those special areas of the brain where there is no blood-brain barrier, the so-called circumventricular organs which we shall mention later on. If you look, you see that the capillaries have got wide fenestrations in between the endothelial cells. That is the first thing we notice. Secondly, we notice that the basement membrane around them is quite permeable. And the third thing we notice is the foot processes do not form a complete ring around the capillaries. So therefore, as you can see from those red arrows, there is free interchange of substances from the blood to the brain and vice versa. All these structures are highly vascular and the capillaries are highly fenestrated. There is only one exception which we shall mention later on. That is the subcommissural organ where there is non-fenestrated capillaries, but that will be mentioned in the second part of this video. Now, in those areas where there is no blood-brain barrier, there is also another important cellular component which contributes to the functions of the non-blood-brain barrier area. And that cell is known as a tansite. This tansite is a special type of epithelial cell which is located only in the floor of the third ventricle. Instead of ependymocyte, the floor of the third ventricle is lined by tansites. If we look at this picture of the tansite here, we notice that the tansite cell body is on the floor of the third ventricle. It is in contact with the CSF while it has got multiple foot processes. These foot processes wrap themselves around the adjacent capillary. And therefore, they act as a conduit between the capillary and the CSF. They allow substances to flow in either direction. So we will see the role of these tansites also in those areas where there is no blood-brain barrier. That brings us to this terminology which we call as circumventricular organs. After the experiment of Aerolik, he noticed that most of these areas which picked up the stain from the dye were around the third ventricle. And one of them was around the fourth ventricle. That's why these structures came to be known as circumventricular organs. They are made by CSF on one side and they are in contact with the capillaries on the other side. And the various circumventricular organs that we shall describe in the subsequent part of our videos are one, median eminence of tuberosinarium, the organum vascularism of lamina terminalis, the sub-phonical organ, the pineal gland, the sub-commissural organ and area post-trema. Finally, why do we need these areas? What are the functions of these circumventricular organs? They are chemo-sensitive organs. They allow sampling of blood and therefore they provide endocrine feedback and regulation. They contribute to the homeostasis of the body, metabolic regulation, fluid and electrolyte balance and they also detect toxins in blood. And finally, it is also postulated that some of them may play a role in CSF circulation. So stay tuned for the second video. This is the first part just to give you an outline of what is the blood-brain barrier and how does it differ from those areas where there is no blood-brain barrier.