Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury

Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord... AbstractOBJECTIVEExperimental 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.METHODSExperimental 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.RESULTSThe 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.CONCLUSIONPharmacological 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury

Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury

Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury Arun Paul Amar, M .D ., Michael L. Levy, M .D. D e p a r t m e n t o f N e u r o l o g i c a l S u r g e r y , U n i v e r s i t y o f S o u t h e r n C a l i f o r n i a , L o s A n g e le s , C a l if o r n ia OBJECTIVE: Experimental models and clinical observations of acute spinal cord injury (SCI) support the concepts of primary and secondary injury, in w hich the initial mechanical insult is succeeded by a series of deleterious events that promote progressive tissue damage and ischemia. W hereas the primary injury is fated by the circum stances 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 m olecular events that mediate the pathogenesis of SCI are logical targets for pharmacological manipulation and include glutamate accum ulation, aberrant calcium fluxes, free radical formation, lipid peroxi­ dation, 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...
Loading next page...
 
/lp/ou_press/pathogenesis-and-pharmacological-strategies-for-mitigating-secondary-uL0VwDNYNU
Publisher
Congress of Neurological Surgeons
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199905000-00052
Publisher site
See Article on Publisher Site

Abstract

AbstractOBJECTIVEExperimental 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.METHODSExperimental 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.RESULTSThe 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.CONCLUSIONPharmacological 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.

Journal

NeurosurgeryOxford University Press

Published: May 1, 1999

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial