John van Geest Centre for Brain Repair

School of Clinical Medicine

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What is Brain Repair?

How is nerve fibre conduction blocked?

Many nerve fibres in the brain and spinal cord are insulated by myelin, which is a sheath formed by glial cells called oligodendrocytes.  If this insulating sheath is removed, the nerve fibres cannot conduct nervous impulses.

This happens particularly in multiple sclerosis. In this disease an autoimmune process kills oligodendrocytes (myelin-forming cells) in small patches of the brain and spinal cord, leaving the nerve fibres uninsulated and therefore non-conducting. These patches, known as plaques, are usually only a few millimetres in size, but they can occur frequently anywhere in the brain or spinal cord. The plaques do not generally repair themselves. The result is small regions in which the nerve fibres do not conduct. These give symptoms which depend on where they are, and the function of the nerve fibres that are affected.

Why does the brain need repairing?

Most types of neurological damage lead to¬†permanent disability. People with spinal injuries never recover from their paralysis and loss of sensation, those suffering from Parkinson’s disease will never recover from the condition and always be reliant on medicines, patients with multiple sclerosis never recover fully from their lesions. This is because the brain and spinal cord lack the ability to heal themselves after injury. Recall that the three main causes of loss of function after damage to the nervous systems are: loss of neurons, cutting of axons and loss of insulation on axons. None of these deficits heals spontaneously.

  1. Lost neurons are not replaced. Neurons are created during embryonic development, but after that time we have almost no ability to make new ones. Thus, when large numbers of neurons are killed they cannot be replaced, and the disability that results from their loss is permanent.
  2. Cut nerve fibres also cannot regenerate. In order to restore the function of cut nerve fibres, they need to be able to regrow from the site of the cut back to their original connection site. Nerve fibres in the brain and spinal cord are completely unable to regenerate. Therefore nerve fibres cut in the spinal cord as a result of a cord injury will never regrow, and people with cord injuries will be paralysed for life.
  3. Lost insulating myelin is not fully replaced. When the oligodendrocytes that form myelin are lost as a result of multiple sclerosis, the brain and spinal cord have a very limited ability to replace them. Therefore many of the multiple sclerosis plaques never become re-myelinated. This means that the nerve fibres that pass through these plaques can never conduct nerve impulses normally, and eventually many of these demyelinated nerve fibres will die.

 

Left: nerve fibres trying (unsuccessfully) to re-grow after damage
Right: improved growth after experimental treatment with two molecules that remove some of the restrictions on growth. (Rong-rong Zhao, PhD student)

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