Severely deranged cardiovascular function often follows spinal cord injury, the most serious manifestation of which are """"""""hypertensive crises"""""""" in which ordinarily innocuous stimuli provoke widespread, paroxysmal increases in sympathetic activity and hypertension severe enough to lead to stroke. The advent of treatments that promise spinal cord regeneration raises an additional concern. There is no evidence that regenerating spinal pathways will, or will not, make connections to appropriate spinal neurons. This raises the issue of whether during and after regeneration descending axons might activate inappropriate spinal neurons, resulting in cardiovascular severe dysfunction. These two concerns, hypertensive crises after spinal cord injury and the potential for dangerous cardiovascular responses due to inappropriate regeneration motivate our attention to spinal sympathetic systems. We propose three aims. First, we will determine whether spinal cord injury increases the number, distribution, and complexity of interconnections of spinal """"""""sympathetic interneurons,"""""""" neurons that are likely to be involved in generating aberrant sympathetic activity after spinal injury. More numerous interconnections between these neurons would help explain the abnormal synchrony with which different levels of the spinal cord respond to stimuli after injury. Second, we will determine whether spinal cord injury causes nerve fibers from the skin to make new, more dense, and more widespread synapses on spinal sympathetic interneurons. More dense or widespread synapses would help explain the greater sensitivity of spinal sympathetic systems to normally innocuous stimuli. Third, we will determine which pathways from the brain synapse on sympathetic interneurons. Not only will this provide new information on the how the brain regulates sympathetic activity, but it will elucidate baseline connections in spinally intact animals that can be compared with connections that are formed during therapeutic regeneration or sprouting.
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