Plasticity of the central nervous system and functional recovery following spinal cord injury.

摘要

The focus of these studies was on plasticity of the central nervous system and functional recovery following a low thoracic hemisection in the cat. Functional recovery was assessed by characterizing the obstacle negotiation task which can be achieved using supraspinal and/or intraspinal networks for voluntary clearance or the stumbling corrective response respectively. Following thoracic hemisection, significant changes were seen in the cat's ability to clear an obstacle and the partial recovery seen suggested underlying plasticity was likely. To identify potential substrates that may contribute to the recovery, populations of neurons that bridged the lesion segment were identified using a retrograde tracer. Populations of long and short propriospinal neurons (PSNs) and rubrospinal tract (RST) neurons were assessed. All systems showed an immediate, significant decrease in the number of neurons with axons below the level of the lesion. The decrease was permanent in the long PSNs. However, the number of short PSNs increased significantly post-injury. The number of neurons contralateral to the lesion was significantly greater than that seen in normal controls suggesting that in addition to regeneration and collateral sprouting of axons in passage, neurons with axons that normally terminate rostral to the lesion were extending branches bridging the lesion site. Similar significant changes were seen in the non-axotomized red nucleus. These neurons represent a novel substrate that may have contributed to new circuitry which supported the functional recovery seen. Traditionally, studies focus on the lesion environment when identifying substrates that inhibit axonal growth following injury. However, areas distant to the lesion undergo Wallerian degeneration. To understand how this may affect the distant spinal substrates, the glial responses and extracellular matrix changes in the cervical and lumbar spinal cord following a thoracic injury were assessed. Using immunohistochemical techniques, increases in activated glial cells as well as chondroitin sulfate proteoglycans were identified in areas undergoing Wallerian degeneration. Furthermore, these changes were delayed with respect to the timing of these same changes at the lesion site. This identifies the importance of considering injury-induced changes in substrates distant to the lesion when assessing plasticity and designing treatments to promote long distance regeneration. Understanding the potential for plasticity and the putative impact of cellular and extracellular matrix changes along the length of the spinal cord following injury are important to understand recovery that is seen and critical to the development of therapeutic interventions to enhance functional recovery.