Effect of graded spinal cord compression on cardiovascular neurons in the rostro-ventro-lateral medulla

In patients with spinal cord injury, cardiovascular disturbances such as hypotension, bradycardia and autonomic dysreflexia can be directly linked to abnormalities of central autonomic control. To date, the changes in bulbospinal innervation of sympathetic preganglionic neurons after compressive spinal cord injury have not been investigated. Thus, we examined the effect of varying severity of compressive spinal cord injury on neurons of the rostro-ventro-lateral medulla, a nucleus of key importance in cardiovascular control. Adult rats with 20 g, 35 g and 50 g clip compression injuries (n= 18) of the cord at T1 and uninjured controls (n=13) were studied. Neurons in the rostro-ventro-lateral medulla with preserved spinal connections eight weeks after spinal cord injury were identified by retrograde labelling with 4% FluoroGold introduced into the cord at T6. Bulbospinal neurons in the rostro-ventro-lateral medulla were also examined immunocytochemically for the adrenaline-synthesizing enzyme phenylethanolamine-N-methyltransferase. In control rats an average of 451+/-12 rostro-ventrolateral medulla neurons were phenylethanolamine-N-methyltransferase positive. Of these, 213+/-6 projected to the T6 spinal cord. The number of rostro-ventro-lateral medulla neurons retrogradely labelled by FluoroGold decreased as a linear function of severity of spinal cord injury (r= -0.95; P<0.0001). After 50g spinal cord injury at T1, only 7+/-1 rostro-ventro-lateral medulla neurons were labelled by FluoroGold, of which 6+/-1 were phenylethanolamine-N-methyltransferase positive. Moreover, the number of phenylethanolamine-N-methyltransferase positive rostro-ventro-lateral medulla neurons decreased to 361+/-16 after 50 g spinal cord injury. We conclude that compressive spinal cord injury results in disconnection of rostro-ventro-lateral medulla neurons, which project to the thoracic spinal cord, and that these changes vary with the severity of injury. The majority of these axotomized rostro-ventro-lateral medulla neurons maintain their immunopositivity for the adrenaline-synthesizing enzyme phenylethanolamine-N-methyltransferase.