Neurotrophic factors for treatment of neurotrauma

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released November 24, 1997; last updated August 17, 2017; expires August 17, 2020

Overview

This article starts with a review of the experimental evidence for the role of neurotrophic factors in the pathomechanisms of CNS injury at the molecular level. The developing brain responds to a mild injury by modifying factors related to synaptic plasticity, and regions remote from the site of injury express neurotrophic signals potentially needed for compensatory responses. Various studies of neurotrophic factors in traumatic brain injury have shown that they have a neuroprotective action and enhance cellular systems involved in the maintenance of Ca(2+) homeostasis and free radical metabolism. The levels of neurotrophic factors are increased following injury, indicating that this has something to do with repair mechanisms following spinal cord injury. Implantation of encapsulated genetically engineered fibroblasts producing neurotrophic factors has been shown to accelerate recovery from traumatic spinal cord injury in an adult rat. Neurotrophic factors also have well-documented abilities to support neuron survival and stimulate neurite outgrowth, making them excellent candidates for use in repairing injured nerves.

Key points

 

• There are changes in neurotrophic factors in the brain and the spinal cord following acute trauma.

 

• Reductions in neurotrophic factor concentration in tissues are reflected in CSF examination and may possibly be detected by examination of serum.

 

• Beneficial effects of stem cells in traumatic injuries of the central nervous system are attributed to release of neurotrophic factors.

 

• These findings form the basis of the investigative use of neurotrophic factors for neuroprotection and neuroregeneration in management of central nervous system trauma.

Historical note and terminology

A trophic factor can be generally defined as any molecule that supports the survival of neurons. Nerve growth factors are polypeptides that regulate the proliferation, survival, migration, and differentiation of cells in the nervous system. Most of the studies have focused on the effect of growth factors on neuronal survival and maintenance, hence, the term “neurotrophic factors.” A neurotrophic factor is synthesized by, and released from, target cells of the neurons, bound to specific receptors, then internalized and transported by retrograde axonal transport to the cell soma where multiple survival-promoting effects are initiated.

Growth factors termed “cytokines” have also been found to modulate neuronal processes. Originally, cytokines were considered to be derived solely from the cells of the immune system, but now they are known to be produced by the cells of the CNS also. In this article, the term “neurotrophic factors” will be used in a broad sense to cover neurotrophins (nerve growth factor, brain-derived neurotrophic factor, neurotrophins), growth factors, and other substances that promote survival and repair of the cells of the nervous system.

Neurotrophic factors are the most important of all the factors influencing regeneration of CNS following trauma by facilitating cell survival, axon growth-cone stimulation, and synapse regeneration (Jain 2016). The role of neurotrophic factors in injuries to the nervous system will be described according to the involvement of the brain, the spinal cord, or the peripheral nerves. "Traumatic brain injury" is the term applied to a brain injury caused by external physical trauma, and "spinal cord injury" is the term applied to an injury to the spinal cord induced by physical trauma.

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