An Overview of Pharmacological Approaches for Management and Repair of Spinal Cord Injuries

Article excerpt

Spinal cord injury (SCI) leads to loss of nervous tissue and consequently to catastrophic neurological deficits. Up to now there is no definite treatment available that restores the loss of function to a degree that an independent life can be guaranteed.

This justifies the cost of research into the new modalities for a treatment of SCIs. In current paper, recent developments and new approaches in pharmacological therapy have been reviewed

Key words: Medication therapy management, Spinal cord injury

Iran J Psychiatry 2010; 5:119-127

Spinal cord injury (SCI) results in devastating neurological deficits and disabilities. The annual incidence of SCI in developed countries varies from 11.5 to 53.4 per million populations (1-3). As the life expectancy of survivors is increasing, information on the prevalence of SCI is becoming more important, but few prevalence studies are available.

Prevalence rate ranged from 11 to 112 per 100000 populations (4-7).

The social and economic impact of SCI extends to involve, not just the patient and the immediate family, but also the community and society at large (8, 9).

In 1990, it was estimated that the cost of managing all SCIs in the United States was 4 billion dollars annually.

Therefore, it seems rational to invest for the development of new treatment modalities that improve the condition of these patients.

(10).

PATHOPHYSIOLOGY

There are two types of injury that may cause damage to the spinal cord. These include primary and secondary injuries (8). Primary injuries occur at the time of

mechanical trauma to the spinal cord. Secondary injuries are caused by a series of cellular and biochemical reactions that are provoked by the primary injuries (11). Among these are hypoxia, accumulation of excitatory neurotransmitters, hyperthermia, imbalance in intracellular electrolytes , increased level of opioid (dynorphins)at the site of injury, free radical formation and lipid peroxidation, microvascular alteration, anemia, activation of inflammatory cells associated with cytokins and activation of calpain and caspaces and apoptosis (12, 13).

Inhibitory elements in the CNS inhibit damaged nerve fibers to exhibit regenerative sprouting .Nogo-A (neurite out growth inhibitor), MAG( myelin-associated glycoprotein), OMgp (oligodendrocyte-myelin glycoprotein) ,chondroitin sulfate proteoglycan which are exposed after the injury, are proteins that play such a role(14-16).

APPROACH TO TRAETMENT

Surgical decompression of the cord and restoration of its normal alignment, together with stabilization of the spine when indicated, accompanied by physical and occupation therapy, and managing psychologic, urologic and proctologic problems are the standard managing methods for spinal cord injury patients (17, 18).

Several attempts have been made to modulate the mechanisms leading to the secondary injury. These are: pharmacological interventions, neutralization of the inhibitory proteins, cell therapy, and gene therapy (19-22).

Considering the key pathophysiological mechanisms that contribute to neurological deficits after SCI, it seems that promising drug-based therapeutic approaches,(that we explain in this paper), including regenerative strategies to neutralize myelin-mediated neurite outgrowth inhibition, neuroprotective strategies to reduce apoptotic triggers, targeting of cationic/glutamatergic toxicity, anti-inflammatory strategies and the use of approaches that stabilize disrupted cell membranes could be considered effective ways to prevent further damage to the spinal cord and promote its repair(23, 24).

PHARMACOLOGICAL INTERVENTION

Methylprednisolone

Methylprednisolon (MP) has been used to treat different neurological impairments. Its mechanism of action has been explained by anti inflammatory and antioxidant properties in addition to inhibitory effects on lipid peroxidation (25). …