Copyright
©The Author(s) 2015.
World J Orthop. Jan 18, 2015; 6(1): 42-55
Published online Jan 18, 2015. doi: 10.5312/wjo.v6.i1.42
Published online Jan 18, 2015. doi: 10.5312/wjo.v6.i1.42
Table 1 Secondary ınjury mechanisms involved in the pathophysiology of spinal cord injury
| Systemic effects |
| Heart rate - brief increase then prolonged bradycardia |
| Blood pressure - brief hypertension then prolonged hypotension |
| Peripheral resistance - decreased |
| Cardiac output - decreased |
| Local vascular damage of the cord microcirculation |
| Mechanical disruption of capillaries and venules |
| Hemorrhage - especially gray matter |
| Loss of microcirculation - mechanical, thrombosis, vasospasm |
| Biomechanical changes |
| Excitotoxicity - glutamate |
| Neurotransmitter accumulation |
| Catecholamines - noradrenaline, dopamine |
| Arachidonic acid release |
| Free radical production |
| Eicosanoid production |
| Prostaglandins |
| Lipid peroxidation |
| Endogenous opioids |
| Cytokines |
| Electrolyte shifts |
| Increased intracellular calcium |
| Increased intracellular potassium |
| Increased intracellular sodium |
| Inflammatory response |
| Free radical generation |
| Macrophages |
| Axonal breakdown, removal of myelin debris |
| Release of cytokines |
| Glial cell activation |
| Cytotoxic effects on oligodendrocytes |
| Wallerian degeneration |
| Edema |
| Apoptosis |
| Loss of energy Metabolism |
| Decreased ATP production |
Table 2 American spinal ınjury association ımpairment scale
| A = Complete: No motor or sensory function is preserved in the sacral segments |
| B = Incomplete: Sensory but not motor function is preserved below the neurological level and includes sacral segments |
| C = Incomplete: Motor function preserved below the neurological level; more than half the key muscles below the neurological level have a muscle grade less than 3 |
| D = Incomplete: Motor function preserved below the neurological level; at least half the key muscles below the neurological level have a muscle grade of 3 or more |
| E = Normal: Motor and sensory function |
Table 3 Pharmacotherapy of acute spinal cord injury and mechanism(s) of action
| Methylprednisolone |
| Inhibition of lipid peroxidation/antioxidative/anti-inflammatory |
| Properties decrease ischemia, support energy metabolism, inhibit neurofilament degradation, decrease intracellular Ca, decrease PG F/ TxA, increase spinal neuron excitability, decrease cord edema |
| Ganglioside GM-1 |
| Stimulate neurite regrowth/regeneration |
| Opioid receptor antagonists |
| Antagonize the increase in endogenous opioid levels after SCI (opioid receptor activation can contribute to excitotoxicity) |
| TRH and its analogs |
| Antagonize endogenous opioids, platelet-activating factor, peptido- leukotrienes and excitatory amino acids |
| Nimodipine |
| Decrease intracellular Ca2+ accumulation, attenuate vasospasm |
| Gacyclidine (GK11) |
| Antagonism of glutamate receptors |
| Magnesium |
| Replace Mg2+ depletion that is common after SCI, diminish intracellular Ca2+ accumulation, block N-methyl-D-aspartate receptor ion channel, modulate binding of endogenous opioids |
| Hypothermia |
| Reduce extracellular glutamate, vasogenic edema, apoptosis, neutrophil and macrophage invasion and activation, and oxidative stress |
| Minocycline |
| Inhibition of microglial activation, inhibition of cytochrome c release |
| Erythropoietin |
| Reduced apoptosis and lipid peroxidation |
| Estrogen |
| Not clearly known |
| Progesterone |
| Reduce the production of inflammatory cytokines |
| Cyclooxygenase inhibitors |
| Prevents/antagonizes decreased blood flow/platelet aggregation from production of arachidonic acid metabolites |
| Riluzole |
| Blockade of voltage-sensitive sodium channels and antagonism of presynaptic calcium-dependent glutamate release |
| Atorvastatin |
| Prevents neuronal and oligodendrocytic apoptosis |
| Antioxidants |
| Antagonize deleterious effects of free radicals (lipid eroxidation, reperfusion injury, etc.) |
Table 4 Cellular transplantatıon therapıes spinal cord injury
| Schwann cells | Secrete growth factors, reestablish microenvironment |
| Olfactory ensheathing cells | Promoting axonal regeneration |
| Bone marrow cells | Produce neuroprotective cytokines |
| Stimulated macrophages | Removal of myelin debris, release of cytokines |
| Oligodendrocyte progenitor cells | Achieve remyelination |
Table 5 Timing of surgery and nonsurgical treatment options of spinal cord injury including pharmacological and cellular therapy
| Timing of surgery |
| Early surgical intervention is safe and feasible which can improve clinical and neurological outcomes and reduce health care costs |
| Early surgical intervention helps minimize the secondary damage caused by compression of the spinal cord after trauma |
| Pharmacological and cellular therapy |
| There is still no accepted pharmacological treatment protocol in SCI |
| Methylprednisolone is the accepted agent used in SCI, however, some criticism has been reported by some authors. It might be used in young patients without accompanying diseases such as diabetes mellitus |
| Cellular treatment studies are continuing |
- Citation: Yılmaz T, Kaptanoğlu E. Current and future medical therapeutic strategies for the functional repair of spinal cord injury. World J Orthop 2015; 6(1): 42-55
- URL: https://www.wjgnet.com/2218-5836/full/v6/i1/42.htm
- DOI: https://dx.doi.org/10.5312/wjo.v6.i1.42