Elsevier

Neuroscience

Volume 111, Issue 4, 6 June 2002, Pages 761-773
Neuroscience

Nervous system reorganization following injury

https://doi.org/10.1016/S0306-4522(02)00025-8Get rights and content

Abstract

Contrary to the classical view of a pre-determined wiring pattern, there is considerable evidence that cortical representation of body parts is continuously modulated in response to activity, behavior and skill acquisition. Both animal and human studies showed that following injury of the peripheral nervous system such as nerve injury or amputation, the somatosensory cortex that responded to the deafferented body parts become responsive to neighboring body parts. Similarly, there is expansion of the motor representation of the stump area following amputation. Reorganization of the sensory and motor systems following peripheral injury occurs in multiple levels including the spinal cord, brainstem, thalamus and cortex. In early-blind subjects, the occipital cortex plays an important role in Braille reading, suggesting that there is cross-modal plasticity. Functional recovery frequently occurs following a CNS injury such as stroke. Motor recovery from stroke may be associated with the adjacent cortical areas taking over the function of the damaged areas or utilization of alternative motor pathways. The ipsilateral motor pathway may mediate motor recovery in patients who undergo hemispherectomy early in life and in children with hemiplegic cerebral palsy, but it remains to be determined if it plays a significant role in the recovery of adult stroke. One of the challenges in stroke recovery is to identify which of the many neuroimaging and neurophysiological changes demonstrated are important in mediating recovery. The mechanism of plasticity probably differs depending on the time frame. Rapid changes in motor representations within minutes are likely due to unmasking of latent synapses involving modulation of GABAergic inhibition. Changes over a longer time likely involve other additional mechanisms such as long-term potentiation, axonal regeneration and sprouting. While cross-modal plasticity appears to be useful in enhancing the perceptions of compensatory sensory modalities, the functional significance of motor reorganization following peripheral injury remains unclear and some forms of sensory reorganization may even be associated with deleterious consequences like phantom pain. An understanding of the mechanism of plasticity will help to develop treatment programs to improve functional outcome.

Section snippets

Transient deafferentation

Transient deafferentation can induce rapid reorganization of the adult CNS and is a useful model to study short-term plasticity changes. During epidural nerve block, neurons in the cat primary somatosensory cortex (S1) that originally responded to stimulation of the anesthetized area became responsive to stimulation of adjacent, unanesthetized areas. These changes reversed 2–4 h after the nerve block (Metzler and Marks, 1979). The findings suggest that cortical representation is dynamically

Reorganization associated with recovery from stroke

Stroke is the third leading cause of death in the United States and is the main cause of long-term disability among adults. Spontaneous recovery usually occurs, although the extent is highly variable. Multivariate analysis suggested that the best predictor of outcome after hemispheric stroke is the severity of initial neurologic deficit (Heinemann et al., 1987). Motor recovery occurs predominantly in the initial weeks to first three months, but can continue at a slower pace throughout the first

Spinal cord injury

Several studies showed that spinal cord injury induced reorganization of the sensory and motor systems. In cats spinalized at T12 level at 2 weeks of age, the deafferented hindlimb region of the S1 was reorganized to a second map of the trunk and forelimb (McKinley et al., 1987). In humans, motor reorganization was demonstrated by TMS in patients with spinal cord injury. In the muscle immediately rostral to the level of injury, MEPs can be elicited from more scalp positions and TMS activated a

Mechanisms for short-term changes

The two main mechanisms proposed to explain reorganization after peripheral lesions are unmasking of previous present but functionally inactive connections and growth of new connections (collateral sprouting). Since the growth of new connections takes time, rapid expansion of muscle representation that occurs within minutes to hours following transient deafferentation in humans (Brasil-Neto et al., 1992, Brasil-Neto et al., 1993, Sadato et al., 1995) or nerve lesions in animals (Merzenich et

Influence of age on the extent of plastic changes

Many studies have demonstrated that age is an important factor in determining the extent of plasticity changes. Injury occurring at a younger age is often associated with more extensive reorganization and better functional outcome. Several animal studies compared the reorganization following injury at different ages. Following denervation of the front paw, the reorganization of the S1 as shown by response of the ‘paw cortex’ to forearm stimulation was more marked in kittens (1.5–3 weeks old)

Functional significance of plasticity following injury

The question of the functional significance of cortical plasticity is an important one. Does such reorganization play a functionally compensatory role? Or, are they an epiphemena with little functional relevance and may even be harmful? We will address this issue for peripheral and CNS injury separately.

Conclusion

Animal and human studies in the last two decades have demonstrated that plasticity reorganization occurs in the mammalian nervous system in response to peripheral and central injuries. While plasticity changes occur at the cortical level, there is also evidence for reorganization at the subcortical, brainstem or spinal cord levels, especially in the somatosensory system in response to peripheral injury. Although the extent of plasticity changes is usually greater in the developing brain than in

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    Present address: Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.

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