Brief discussion about brain

The brain is one of the most complex and magnificent organs in the human body. Our brain gives us awareness of ourselves and of our environment, processing a constant stream of sensory data. It controls our muscle movements, the secretions of our glands, and even our breathing and internal temperature. Every creative thought, feeling, and plan is developed by our brain. The brain’s neurons record the memory of every event in our lives.

Anatomy of the Brain

There are different ways of dividing the brain anatomically into regions. The most common method and divide the brain into three main regions based on embryonic development: the forebrain, midbrain and hindbrain. Under these divisions:

• The forebrain (or prosencephalon) is made up of our incredible cerebrum, thalamus, hypothalamus and pineal gland among other features. Neuroanatomists call the cerebral area the telencephalon and use the term diencephalon (or interbrain) to refer to the area where our thalamus, hypothalamus and pineal gland reside.
• The midbrain (or mesencephalon), located near the very center of the brain between the interbrain and the hindbrain, is composed of a portion of the brainstem.
• The hindbrain (or rhombencephalon) consists of the remaining brainstem as well as our cerebellum and pons. Neuroanatomists have a word to describe the brainstem sub-region of our hindbrain, calling it the myelencephalon, while they use the word metencephalon in reference to our cerebellum and pons collectively.

Before exploring these different regions of the brain, first let’s define the important types of cells and tissues that are the building blocks of them all (Singh, 2006).

Histology

Brain cells can be broken into two groups: neurons and neuroglia. Neurons, or nerve cells, are the cells that perform all of the communication and processing within the brain. Sensory neurons entering the brain from the peripheral nervous system deliver information about the condition of the body and its surroundings. Most of the neurons in the brain’s gray matter are interneurons, which are responsible for integrating and processing information delivered to the brain by sensory neurons. Interneurons send signals to motor neurons, which carry signals to muscles and glands.

Neuroglia, or glial cells, act as the helper cells of the brain; they support and protect the neurons. In the brain there are four types of glial cells: astrocytes, oligodendrocytes, microglia, and ependymal cells.

• Astrocytes protect neurons by filtering nutrients out of the blood and preventing chemicals and pathogens from leaving the capillaries of the brain.
• Oligodendrocytes wrap the axons of neurons in the brain to produce the insulation known as myelin. Myelinated axons transmit nerve signals much faster than unmyelinated axons, so oligodendrocytes accelerate the communication speed of the brain.
• Microglia act much like white blood cells by attacking and destroying pathogens that invade the brain.
• Ependymal cells line the capillaries of the choroid plexuses and filter blood plasma to produce cerebrospinal fluid.

The tissue of the brain can be broken down into two major classes: gray matter and white matter.

• Gray matter is made of mostly unmyelinated neurons, most of which are interneurons. The gray matter regions are the areas of nerve connections and processing.
• White matter is made of mostly myelinated neurons that connect the regions of gray matter to each other and to the rest of the body. Myelinated neurons transmit nerve signals much faster than unmyelinated axons do. The white matter acts as the information highway of the brain to speed the connections between distant parts of the brain and body.

Other important parts of the brain

Cerebrospinal fluid (CSF)

The cerebrospinal fluid (CSF) is a clear, watery liquid that surrounds cushions and protects the brain and spinal cord. The CSF also carries nutrients from the blood to, and removes waste products from, the brain. It circulates through chambers called ventricles and over the surface of the brain and spinal cord. The brain controls the level of CSF in the body.

Meninges

The brain and spinal cord are covered and protected by 3 thin layers of tissue (membranes) called the meninges:

• dura mater – thickest outer layer
• arachnoid layer – middle, thin membrane
• pia mater – inner, thin membrane

CSF flows in the space between the arachnoid layer and the pia mater. This space is called the subarachnoid space.

The tentorium is a flap made of a fold in the meninges. It separates the cerebrum from the cerebellum.

• The supratentorial area of the brain is the area above the tentorium. It contains the cerebrum, the first and second (lateral) ventricles, the third ventricle, and glands and structures in the centre of the brain.
• The infratentorial area is located at the back of the brain below the tentorium. It contains the cerebellum and brain stem. This area is also called the posterior fossa.

Corpus callosum

The corpus callosum is a bundle of nerve fibres between the 2 cerebral hemispheres. It connects and allows communication between both hemispheres.

Thalamus

The thalamus is a structure in the middle of the brain that has 2 lobes or sections. It acts as a relay station for almost all information that comes and goes between the brain and the rest of the nervous system in the body.

Hypothalamus

The hypothalamus is a small structure in the middle of the brain below the thalamus. It plays a part in controlling body temperature, hormone secretion, blood pressure, emotions, appetite, and sleep patterns.

Pituitary gland

The pituitary gland is a small, pea-sized organ in the centre of the brain. It is attached to the hypothalamus and makes a number of different hormones that affect other glands of the body’s endocrine system. It receives messages from the hypothalamus and releases hormones that control the thyroid and adrenal gland, as well as growth and physical and sexual development.

Ventricles

The ventricles are fluid-filled spaces (cavities) within the brain. There are 4 ventricles:

• The first and second ventricles are in the cerebral hemispheres. They are called lateral ventricles.
• The third ventricle is in the centre of the brain, surrounded by the thalamus and hypothalamus.
• The fourth ventricle is at the back of the brain between the brain stem and the cerebellum.

The ventricles are connected to each other by a series of tubes. The fluid in the ventricles is cerebrospinal fluid (CSF). The CSF flows through the ventricles, around the brain in the space between the layers of the meninges (subarachnoid space) and down the spinal cord.

Pineal gland

The pineal gland is a very small gland in the third ventricle of the brain. It produces the hormone melatonin, which influences sleeping and waking patterns and sexual development.

Choroid plexus

The choroid plexus is a small organ in the ventricles that makes CSF.

Cranial nerves

There are 12 pairs of cranial nerves that perform specific functions in the head and neck area. The first pair starts in the cerebrum, while the other 11 pairs start in the brain stem. Cranial nerves are indicated by number (Roman numeral) or name (Chatterjee, 1977).

The Physiology of the Blood-Brain Barrier

The BBB is not one single structure or membrane in the brain, but it is created by the way the blood vessels in the brain are organized. Thus, understanding the BBB requires an understanding of the anatomy and physiology of the blood vessels in the brain. Both large and small capillaries form a richly branched and complex network throughout the entire brain tissue. Like a chimney made of individual bricks, the brain blood vessels consist of a monolayer of endothelial cells that are connected with each other by tight junctions (zonulae occludentes) (Crone and Olsen, 1982). The part of the cell's membrane facing the bloodstream is called the "luminal" membrane (Dehouck, 1990; Arthur, 1987; Tao-Cheng, 1987), and the side which is exposed to the actual brain tissue is called the "abluminal" membrane. This part faces the extracellular liquid of the brain parenchyma where pericytes and end feet of astrocytes surround the blood vessels. The most important site of the BBB lies at the cerebral microvessels, that is, the very fine vessels that have extremely small diameters. Because endothelial cells are very polarized, that is, essentially similar to the epithelium, they exhibit very low pinorytic activity and possess a high number of mitochondria that are needed for the multiple energy-dependenat ctive transport mechanisms found in endothelial cells (Stevard and Wiley, 1981). Peripheral vessels in the rest of the body can much more easily transport molecules across their membrane because they are fenestrated and have many active transcellular transport mechanisms. In contrast, in central blood vessels of the brain, even small molecules like antibiotics have great difficulty crossing the barrier and only a limited number of molecules can actively cross the endothelial cells. Here, the endothelial cells use specific transport systems to allow the influx of glucose, iron, amino acids, peptides, small organic acids, and others. This is necessary so that substances which are critical for brain metabolism and function can gain fast and efficient access to the brain via specific energy-dependent carrier mechanisms at the endothelium (D'Amore, 1990).

The Role of Pericytes

Perirytes, which are located on the abluminal side of the endothelial cells, are also part of the BBB. Pericytes are a physiological heterogeneousc ell population and are found on all micro vessels in nearly every organ (D'Amore, 1990), but they never cover the entire blood vessel. The pericytes, which are located on the "brain side," are encapsulated by the basal membrane of the endothelial cells, and they are responsible for the synthesis and release of different components of the basal membrane and the extracellular matrix such as collagen and glycosaminoglycocan (Stramm et al., 1987). The basal membrane of the endothelial cells and that of the pericytes are closely attached to each other so that both cells have a common basal membrane (Shepro and Morel, 1993). Electron microscopy studies have revealed fenestrations between pericytes and endothelial cells (Frank et al., 1980), and perirytes have contractile properties that may play a role in the regulation of the blood flow. Several molecules are involved in these contractile functions such as actin, myosin, tropomyosin, vimentin, and desmin (Frey et al., 1991; Risau et al., 1992). Pericytes have an important role in the function of the BBB. They are responsible for the maintenance of the barrier function and the stability of the vessel (Kimelberg and Norenberg, 1989).

The Role of Astrocytes

Astrocytes (which are brain glia cells) also contribute to the BBB, and they are attached with their endfeet to the pericytes and the endothelial cells. Astrocytes are glial cells responsible for the homeostasis and the ion regulation in the brain (Kimelberg and Norenberg, 1989), but their end feet cover the blood vessels only partially. In contrast to endothelial cells and pericytes, astrocytes are not connected to other cells by tight junctions, and they do not have a common basal membrane. Therefore, polar molecules (such as proteins) can enter the interstitial liquid and be directly transported to the pericytes and the endothelial cells (Goldstein, 1988). That astrocytes are important for the induction and maintenance of the BBB properties can be deduced from the following observations in cell cultures: in the presence of astrocytes or medium conditioned by astrocytes endothelial cells express markers important for BBB characteristics and develop tight junctions (Dehouck, 1990; Arthur, 1987; Tao-Cheng, 1987). On the other hand, endothelial cells promote the development and differentiation of astrocytes. This interaction between both cell types actually occurs even when there is no contact between the two cell types, indicating that some soluble, extracellular factors are mediators of BBB development.