Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 1999 May;44(5):1027-39; discussion 1039-40.
doi: 10.1097/00006123-199905000-00052.

Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury

A P Amar  1 , M L Levy
Affiliations
Review

Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury

A P Amar et al. Neurosurgery. 1999 May.

Abstract

Objective: Experimental models and clinical observations of acute spinal cord injury (SCI) support the concepts of primary and secondary injury, in which the initial mechanical insult is succeeded by a series of deleterious events that promote progressive tissue damage and ischemia. Whereas the primary injury is fated by the circumstances of the trauma, the outcome of the secondary injury may be amenable to therapeutic modulation. This article reviews the pathogenetic determinants of these two phases of injury and summarizes the pharmacological manipulations that may restore neurological function after SCI.

Methods: Experimental models of SCI and their inherent limitations in simulating human SCI are surveyed. The pathogenesis of primary and secondary injury, as well as the theoretical bases of neurological recovery, are examined in detail. The effects of glucocorticoids, lazeroids, gangliosides, opiate antagonists, calcium channel blockers, glutamate receptor antagonists, antioxidants, free radical scavengers, and other pharmacological agents in both animal models and human trials are summarized. Practical limitations to inducing neural regeneration are also addressed.

Results: The molecular events that mediate the pathogenesis of SCI are logical targets for pharmacological manipulation and include glutamate accumulation, aberrant calcium fluxes, free radical formation, lipid peroxidation, and generation of arachidonic acid metabolites. Enhancement of neural regeneration and plasticity comprise other possible strategies.

Conclusion: Pharmacological agents must be given within a narrow window of opportunity to be effective. Although many therapeutic agents show potential promise in animal models, only methylprednisolone has been shown in large, randomized, double-blinded human studies to enhance the functional recovery of neural elements after acute SCI. Future therapy is likely to involve various combinations of these agents.

PubMed Disclaimer