Little is known about the effects of protein-energy malnutrition (PEM) developing after stroke on brain recovery. The goal of this project was to develop two experimental models in the adult rat to allow evaluation of nutritional effects on post-stroke recovery: (1) a PEM model, and (2) a photothrombotic stroke model. Experiment 1 examined the hypothesis that a diet containing either 1% or 0.5% protein will produce an acute state of mild-moderate PEM in adult rats. Male, Sprague-Dawley rats (16 wk) were trained in the Montoya staircase before being randomized to diets containing 0.5% (n=8), 1% (n=8), or 12.5% protein (n=10 [CON]) for 31d. Both low protein diets increased liver lipid content (p< 0.001) and decreased food intake (p= 0.005) and body weight (p< 0.001) compared to the 12.5% protein diet. The 0.5% protein group best mimicked the stroke patient, as judged by decreased serum albumin (p= 0.018) and an acute decrease in mean (±SEM) body weight (g) by d7 (0.5%= 424±15; 1%= 428±14; CON= 477±10; p = 0.011). Increased concentrations of the positive acute phase proteins, alpha-2-macroglobulin and alpha-1-acid glycoprotein, were greatest in the 0.5% group (p< 0.001). No differences were observed in the Montoya test on d3, 15, or 30 (p= 0.26). Values on d30 were: 0.5%= 109.5±4.4% of pre-diet performance; 1%= 97.2±5.5%; CON= 98.5±10.2%. Experiment 2 tested the hypothesis that targeted laser irradiation and 30 mg/kg of rose Bengal injection will cause an infarct in the forepaw region of the cortex with accompanying functional deficits. Male adult rats trained in the Montoya staircase were randomized to ISCHEMIA (n=15) or SHAM (n=3) surgery. A cortical infarct occurred in 86% of rats, with some misplacement and variability in volume (5.7-12.8 mm3). Forepaw impairments were confirmed by decreased performance in the staircase at d3 (34.3±7.3 % of pre-stroke performance, p<0.001) and diminished use in the cylinder test (30.3±4.0% affected limb use versus 53.9±1.93% prestroke, p< 0.001). At d30, mean recovery was incomplete in the staircase (p< 0.001). These experimental models, with additional refinements, can be used to address the hypothesis that deteriorating nutritional status after a stroke interferes with brain recovery.

No description available.

No description available.

No description available.

No description available.

To investigate the roles of different dorsal spinal pathways in controlling movements in rats, I performed lesions of specific spinal pathways and measured the behaviour abilities of rats using different sensorimotor behavioural tests. The first experiment was designed to understand the contribution of sensory pathways traveling in the dorsal funiculus during locomotion and skilled movements using sensitive behavioural tests. I demonstrated that ascending sensory fibers play an important role during overground locomotion and contribute to skilled forelimb movements. The second experiment compared the differences in sensorimotor abilities caused by dorsal funicular lesions performed at two different levels of rat spinal cord. My results showed that the pathways present in the cervical and thoracic dorsal funiculus exert different functional effects over control of limb movement during locomotion. The third experiment investigated the compensatory potential of dorsal funicular pathways after dorsolateral funicular injuries in rats. My results showed that dorsal funicular pathways do not compensate for loss of dorsolateral pathways during the execution of locomotor tasks, though there is indirect evidence that rats with dorsolateral funicular lesions might rely more on ascending sensory pathways in the dorsolateral funiculus during skilled forelimb movements. Finally, the fourth experiment was designed to investigate the compensation from dorsolateral funicular pathways after injuries to pyramidal tract in rats. I demonstrated that pathways running in the spinal dorsolateral funiculus do provide compensatory input to spinal circuitry to maintain skilled reaching abilities after lesions of the pyramidal tract but these same pathways do not appear to compensate during either overground locomotion or skilled locomotion. Thus, this compensatory response is task-specific. These results highlight the fact that behavioural context determines the nature of compensation from spared pathways after spinal cord injuries.

To investigate the roles of different dorsal spinal pathways in controlling movements in rats, I performed lesions of specific spinal pathways and measured the behaviour abilities of rats using different sensorimotor behavioural tests. The first experiment was designed to understand the contribution of sensory pathways traveling in the dorsal funiculus during locomotion and skilled movements using sensitive behavioural tests. I demonstrated that ascending sensory fibers play an important role during overground locomotion and contribute to skilled forelimb movements. The second experiment compared the differences in sensorimotor abilities caused by dorsal funicular lesions performed at two different levels of rat spinal cord. My results showed that the pathways present in the cervical and thoracic dorsal funiculus exert different functional effects over control of limb movement during locomotion. The third experiment investigated the compensatory potential of dorsal funicular pathways after dorsolateral funicular injuries in rats. My results showed that dorsal funicular pathways do not compensate for loss of dorsolateral pathways during the execution of locomotor tasks, though there is indirect evidence that rats with dorsolateral funicular lesions might rely more on ascending sensory pathways in the dorsolateral funiculus during skilled forelimb movements. Finally, the fourth experiment was designed to investigate the compensation from dorsolateral funicular pathways after injuries to pyramidal tract in rats. I demonstrated that pathways running in the spinal dorsolateral funiculus do provide compensatory input to spinal circuitry to maintain skilled reaching abilities after lesions of the pyramidal tract but these same pathways do not appear to compensate during either overground locomotion or skilled locomotion. Thus, this compensatory response is task-specific. These results highlight the fact that behavioural context determines the nature of compensation from spared pathways after spinal cord injuries.