This NICHD small grants program application seeks to investigate the hypothesis that genotype affects the development of autonomic dysreflexia. Autonomic dysreflexia is a life-threatening condition that occurs in up to 85% of people with severe spinal cord injuries above the T6 segment. The most dangerous characteristic of autonomic dysreflexia is severe hypertension. A number of stimuli can elicit autonomic dysreflexia, but the most common are urinary bladder distention or irritation and colorectal distention. Although autonomic dysreflexia is well characterized, the mechanisms involved are not known. Previously experiments from this laboratory indicated that Wistar rats developed autonomic dysreflexia in response to colorectal distention following an upper thoracic spinal cord transection, but Sprague-Dawley rats did not develop autonomic dysreflexia. Thus, there is the possibility that there is a genetic component to the development of autonomic dysreflexia. The hypothesis of the proposal is that genotype effects the development of autonomic dysreflexia and two specific aims will address this hypothesis.
In SPECIFIC AIM 1, two inbred rat's strains that have different degrees of autonomic dysreflexia will be identified. The development of autonomic dysreflexia following spinal transection in ten inbred strains of rats will be systematically determined. Ideally, a strain that exhibits a large dysreflexic response and one that displays little or no response will be found. These two strains will then be used for SPECIFIC AIM 2 in which the investigators will identify appropriate simple strand length polymorphisms (SSLPs) to use for genetic linkage analysis. The SSLPs will be used as genetic markers. The goal is to identify SSLP that are polymorphic between the two strains and that are evenly spaced along each chromosome.
This aim will identify the specific SSLPs that will be used to determine the genotype of F2 offspring with a cross between these two rat strains in future projects. Successful completion of these aims will provide new information indicating that there may be genes that predict the magnitude of autonomic dysreflexia following spinal cord injury.
| Landrum, L M; Jones, S L; Blair, R W (2002) The expression of Fos-labeled spinal neurons in response to colorectal distension is enhanced after chronic spinal cord transection in the rat. Neuroscience 110:569-78 |
