Neuroprotection of spinal neurons against blunt trauma and ischemia

Each year in the Unites States there are over 10,000 new cases of para- and quadriplegia, and more than 100,000 cases of limited, but permanent, neurological losses. Many of these losses result from blunt trauma and ischemia to the spinal cord which leads to neuron death. Although blunt trauma directly kills neurons due to the physical trauma, over the subsequent 48 hours an even larger population of neurons dies due to secondary causes. One of leading triggers of this neuron death is ischemia due to the disruption of the blood circulation. Selective, but unavoidable, spinal cord ischemia occurs during thoracoabdominal surgery to repair aortic aneurysms. This ischemia leads to neuron death, functional neurological loss, and paraplegia in up to 33% of the cases. Thus, both blunt trauma and induced ischemia have similar triggers of neuron death. To reduce the neurological losses resulting from ischemia mechanisms must be found to make spinal neurons more tolerant to ischemic insult and other secondary causes of neuron death. In this review we discuss mechanisms being developed, predominantly using animal models, to provide neuroprotection to prevent neurological losses following blunt trauma and during induced spinal cord ischemia. In parallel, our own experiments are looking at neuroprotective techniques using adult human neurons. We believe the optimal neuroprotective approach will involve the perfusion of the ischemic region of the spinal cord with a hypothermia solution containing a combination of pharmacological agents.