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Pharmacological neuroprotection for spinal cord injury

Spinal cord injuries can cause the catastrophic loss of motor and sensory function. The neurological deficits that result are the consequence of not only the primary injury to the spinal cord, but also a complex milieu of secondary pathological processes that are now beginning to be understood. The major mechanisms that underlie this secondary pathology include vascular disruption, ischemia, oxidative stress, excitotoxicity, and inflammation. In light of this, the fact that this secondary pathology occurs after the initial impact makes it potentially amenable to therapeutic intervention. Pharmacotherapies may attenuate some of these processes and minimize secondary damage.

Some of the promising treatments that are emerging for acute spinal cord injury are drugs that are already used by physicians for the treatment of unrelated diseases. These drugs, which have already been established to be safe for humans, offer the unique advantage over other novel therapeutic interventions that have yet to be tested in humans. This would save a tremendous amount of time and money needed for human safety studies, if considered as a treatment for spinal cord injury. Examples of such drugs include minocycline (an antibiotic), erythropoietin (a recombinant hormone used to treat anemia), and statins (a popular class of blood cholesterol reducers), all of which have demonstrated the ability to attenuate the various pathophysiological processes initiated after trauma to the central nervous system.

In a series of studies, erythropoietin, darbepoetin, atorvastatin, simvastatin, and minocycline were all evaluated for their ability to improve neurologic recovery in a clinically relevant model of spinal cord injury. My experiments revealed that erythropoietin, darbepoetin, atorvastatin and minocycline did not significantly improve neurological recovery. These negative results were in stark contrast to the positive findings which had been published in the literature suggesting that differences in experimental models and methodology influence the neuroprotective efficacy of these drugs. Simvastatin, on the other hand, demonstrated significant improvements in locomotor and histological outcomes. Although this is indeed exciting, the results were modest at best. My results highlight the need for further preclinical work on the above treatments to refine and optimize them prior to proposing them for human testing.
Date05 1900
CreatorsMann, Cody Mandeep
PublisherUniversity of British Columbia
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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