Current pharmaceutical design
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A spinal cord injury leads to disturbances of sensory and motor signals due to the damage to white matter and myelinated fiber tracts. Moreover, the damage to gray matter causes segmental loss of interneurons of dorsal horn and motoneurons and restricts the therapeutic options. Neuroprotective strategies have the potential to improve the neurological outcome of patients. ⋯ This review includes consideration of: 1) basic concepts of the pathophysiological mechanisms following spinal cord injury and 2) anesthetics and analgesics displaying neuroprotective potential. In particular, we review the application of isoflurane as an inhalational neuroprotectant and discuss evidence for the neuroprotection provided by barbiturates. In addition, 3) recent advances in stem cell biology, neural injury and repair, and progress toward the development of neuroprotective and regenerative interventions are the basis for increased optimism.
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Since several clinical data have suggested that the incidence of neurological deficit after aortic surgery has not changed appreciably over the last 50 years, anesthesiologists as well as vascular surgeons have attempted to resolve this clinically important issue by employing various strategies to prevent ischemic spinal cord injury. With respect to inhalational anesthetics, it is thought that isoflurane as well as sevoflurane preconditioning might provide neuroprotective effects against spinal ischemia via activation of TWIK-related K channels-1 or the potassium ATP channel. Glutamate receptor antagonists, including ketamine, could also potentially provide some neuroprotection against spinal ischemia. ⋯ Inhaled nitric oxide (iNO) therapy (40-80ppm), a common treatment for pulmonary hypertension, has been reported to prevent ischemic brain injury in animal studies by selective dilation of collateral arterioles. The vasodilating effects of iNO on the central nervous system might enhance the "collateral network" in the spinal cord during aortic cross-clamp, potentially protecting the spinal cord. In conclusion, some anesthetics, especially inhalational anesthetics, may provide neuroprotective effects against spinal cord ischemia, but administration of neuraxial opioid after spinal cord ischemia might exacerbate neurological dysfunction.