The Effects of Encephalitis on the Brain

In order to understand the effects of encephalitis on the brain, it can be helpful to understand how the brain works. The brain is an amazing organ, it controls everything you think, feel and do. All the various parts that make up the brain work together to help people communicate move and behave.

The brain is made up of approximately 100 billion nerve cells or “neurons” and each neuron makes between 1,000 and 10,000 connections to other neurones. This “neural network” is similar to the way roads connect to make road networks.

At birth all the neurons you will ever have are present but there are very few connections. During early development, the neurons form trillions of connections. These connections are fine-tuned by the neurons' electrical activity: useful connections are maintained or added, while others often disappear. Axons that become regularly used are gradually covered by a protective coating, the myelin sheath. (A good analogy is the covering a main road with tarmac allowing traffic to flow more freely).

The complexity of the brain is due in part to the intricate system of interconnections between neurons in the different parts of the brain. Neurons communicate with one another via specialised chemicals called neurotransmitters, of which there are several.

The brain is composed of numerous structures, each composed of nerve cells (neurons) and supporting cells called glia. Neurons transmit electrical and chemical signals, and this transmission of signals between neurons is how the brain functions.

Three basic types of glia exist in the brain:

• Oligodendroglia cells wrap axons with myelin. The myelin thus forms a sheath around the axon, facilitating the transmission of electrical signals along a neurone.
  
• Astroglia cells (astrocytes) are found throughout the brain and play many different "housekeeping" roles, providing nourishment and protection for the neurons, structural support, or "scaffolding," for the brain, and also playing an important role in the immune system of the brain.
  
• Microglial cells are important in the brain's injury response as they scavenge cellular debris and help to clean up damage.
  

The brain is protected by a blood-brain barrier which prevents any large molecules passing from the blood into the brain. The barrier is the result of the cells lining blood vessels in the brain. Blood vessels in the rest of the body are lined by cells which fit together very loosely allowing easy movement by quite large bodies to and from the blood. Cells lining blood vessels in the brain fit together very tightly and most substances have to be actively transported through the cells rather than passing between them. The blood-brain barrier acts very effectively to protect the brain from many common infections. Thus, infections of the brain are very rare. The outcome of any virus infection is dependent upon the ability of the virus to cause disease and the response of the immune system. When the immune response is either inadequate or inappropriate, an infection of the brain can cause severe encephalitis.

The immune response evolved to protect organisms against injury and infection. Following an injury or infection a complex cascade of events leads to the delivery of white blood cells to sites of injury to kill potential pathogens and promote tissue repair. However, the powerful inflammatory response also has the capacity to cause damage to normal tissue. Unfortunately the immune response to an infection of the brain can contribute more to the disease process than the infection itself.

In infectious encephalitis, viruses entering neurons utilise components of the cell in order to replicate (make copies of themselves). This uses up energy stores and oxygen and damages the cell. In post-infectious / autoimmune encephalitis the immune system makes antibodies that cause damage to neurons or other brain cells. In both types of encephalitis, by-products of the immune system’s actions (fluid, white blood cells, the contents of dead nerve cells and disabled viruses) can significantly alter the fluid surrounding neurons and affect their functioning. For instance, the characteristics of the cell membrane may be altered, disturbing the electrical properties of the neuron. Swelling resulting from additional fluid entering the brain can interfere with blood supply causing anoxic (lack of oxygen) damage.

The extra unwanted fluids build up rapidly, and glial cells try to absorb the unwanted chemicals and fluids in order to protect neurons from harm, and in the process they swell up too. Glial cells act as sponges and scavengers of toxic by-products, caused by the inflammation but when they become overloaded, they die and then re-release the toxic chemicals back into the fluid, where they kill additional neurons. The extremely high levels of these substances are sufficient to kill vulnerable and weakened neurons by damaging their membranes or by exciting them to a point where they “burn out” and die.

At the site of inflammation and in nearby tissue, there is biological chaos, as the brain tries to adjust and fight the consequences of the damage. The dying cells give off chemicals that activate macrophages (white blood cells), which move from the bloodstream into the injury area, to absorb and eliminate debris. Glial cells and their helpers, which have gathered at the site to clean it up, now begin to form the scar tissue that will remain a part of the brain's new architecture. Sometimes, the glial barriers prevent healthy, remaining neurons from restoring axonal connections. In other cases, nerve terminals cannot pass the scar, and abnormal activity is then generated that can lead to epileptic seizures.