The role of stress in recovery of function after spinal cord injury
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Research has shown that exposure to just 6 minutes of uncontrollable shock 24 hours following contusion injury impairs locomotor recovery and leads to greater tissue loss at the injury epicenter. Uncontrollable shock is known to elevate corticosterone levels in intact rats and corticosterone exacerbates cell death in the hippocampus following injury, suggesting the effects may be related to a stress-induced release of corticosterone. Uncontrollable shock also affects other indices of stress including, spleen weight and norepinephrine, and has been shown to elevate pro-inflammatory cytokines. The present experiments were designed to assess whether uncontrollable shock has similar effects after contusion injury. Experiment 1 examined whether injury itself produced a stress response. Subjects received anesthesia alone, a laminectomy, or a contusion injury. Twenty-four hours later, they were restrained for 6 minutes and blood was collected from the leg. They were sacrificed 24 hours later and spleens were weighed, and plasma corticosterone and norepinephrine were assessed using ELISAs. IL-1! and IL-6 levels at the injury site were also measured using an ELISA. Contusion injury had no impact on any of the biological outcomes. For Experiment 2, subjects received 6 minutes of uncontrollable tailshock or an equivalent amount of restraint. Subjects were sacrificed 6, 24, 72, or 168 hours later. Uncontrollable shock caused a decrease in spleen weight and increased plasma corticosterone within 24 hours. Increases in IL-1! and IL-6 were also seen. Morphine was used in Experiment 3 to block the “psychological” component of uncontrollable shock. Subjects received morphine (20 mg/kg; i.p.) or saline 30 minutes prior to uncontrollable shock and were sacrificed 24 hours later. Morphine did not prevent the consequences of uncontrollable shock and, in some cases, potentiated its effects. The effect of controllability was examined in Experiment 4. After receiving a contusion injury, subjects received either controllable (master) or uncontrollable (yoked) legshock over the course of 2 days. A third group served as unshocked controls. Master subjects did not differ from yoked subjects on any of the biological outcomes measured. Unshocked subjects, however, exhibited an increase in corticosterone, IL-6, and blood monocytes.
Washburn, Stephanie Nicole (2007). The role of stress in recovery of function after spinal cord injury. Doctoral dissertation, Texas A&M University. Available electronically from