Forced and voluntary exercise differentially affect brain and behavior.

The potential of physical exercise to decrease body weight, alleviate depression, combat aging and enhance cognition has been well-supported by research studies. However, exercise regimens vary widely across experiments, raising the question of whether there is an optimal form, intensity and duration of exertion that would produce maximal benefits. In particular, a comparison of forced and voluntary exercise is needed, since the results of several prior studies suggest that they may differentially affect brain and behavior. In the present study, we employed a novel 8-week exercise paradigm that standardized the distance, pattern, equipment and housing condition of forced and voluntary exercisers. Exercising rats were then compared with sedentary controls on measures previously shown to be influenced by physical activity. Our results indicate that although the distance covered by both exercise groups was the same, voluntary exercisers ran at higher speed and for less total time than forced exercisers. When compared with sedentary controls, forced but not voluntary exercise was found to increase anxiety-like behaviors in the open field. Both forms of exercise increased the number of surviving bromodeoxyuridine (BrdU)+ cells in the dentate gyrus after 8 weeks of exercise, although forced exercisers had significantly more than voluntary exercisers. Phenotypic analysis of BrdU+ cells showed no difference between groups in the percentage of newborn cells that became neurons, however, because forced exercise maximally increased the number of BrdU+ cells, it ultimately produced more neurons than voluntary exercise. Our results indicate that forced and voluntary exercise are inherently different: voluntary wheel running is characterized by rapid pace and short duration, whereas forced exercise involves a slower, more consistent pace for longer periods of time. This basic difference between the two forms of exercise is likely responsible for their differential effects on brain and behavior.

Motor enrichment sustains hindlimb movement recovered after spinal cord injury and glial transplantation.

PURPOSE: This study investigated whether enrichment improves hindlimb movement following complete spinal cord transection and transplantation of olfactory ensheathing glia (OEG), with or without a Schwann cell (SC) bridge. METHODS: Motor activity was encouraged through provision of motor enrichment housing (MEH); a multi-level cage containing ramps, textured surfaces and rewards. Hindlimb joint movement was assessed weekly for 22 weeks starting one week post-surgery, comparing rats housed in MEH to those in basic housing (BH). Transganglionic tracer was injected into the crushed right sciatic nerve three days prior to sacrifice, allowing sensory axons in the dorsal columns to be visualized by immunolabeling. Serotonergic axons and glial cells expressing low affinity nerve growth factor receptor were identified by immunolabeling. RESULTS: All rats, having received transplants, recovered some hindlimb movement. Rats housed in BH progressively lost recovered hindlimb function whereas recovered hindlimb movements were sustained in most rats in MEH. In rats transplanted with SCs and OEG, effects of MEH were first significant 14 weeks after injury. In rats transplanted with OEG, a trend was seen from 14 weeks after injury, but this did not reach significance. In all rats, traced sensory axons died back from sites of transplantation and did not regenerate rostrally. Further, in no rat were serotonergic axons observed regenerating into, around or beyond transplants. CONCLUSIONS: Transection and transplantation of SC/OEG or OEG induced recovery of hindlimb function. This recovered hindlimb movement was sustained in rats housed in MEH but was progressively lost in rats housed in BH. Because benefits of MEH were not observed until 14 weeks after injury, long-term assessment of behavior is recommended. BH conditions are not conducive to maintenance of recovered hindlimb function, and MEH should be used in studies of recovery of function following spinal cord injury.

Focal brain injury, FGF-2 and the adverse effects of excessive motor demand on cortical and nigral degeneration: marked protection by delayed intermittent exposure to halothane.

The neuroprotective potential of halothane anesthesia was investigated following unilateral electrolytic lesions to the forelimb representation area of the sensorimotor cortex (FL-SMC). Previously, it was found that the FL-SMC lesion increases substantially in size when the intact forelimb is immobilized with a plaster of paris cast for the first 7 days postlesion, which forces extreme overuse of the impaired forelimb during a time when nonlethally damaged tissue is vulnerable to behavioral demand. Initially, the purpose of this study was to investigate whether intracisternal infusion of basic fibroblast growth factor (bFGF or FGF-2), a potent neurotrophic factor that has been shown to have neuroprotective and plasticity promoting properties in focal stroke and other injury models, could prevent this use-dependent exaggeration of injury. Although intracisternal bFGF (starting 24 h after surgery, twice per week) was not found to produce significant neuroprotective or behavioral effects, the brief exposure to halothane anesthesia (15-20 min) during bFGF or vehicle administration was found to prevent expansion of the lesion size, and to reduce delayed loss of neurons in the substantia nigra pars reticulata (SNr). The data have implications for investigations of the effects of neurotrophic factor in vivo, and other investigations requiring brief, intermittent halothane anesthesia.

Experience-associated structural events, subependymal cellular proliferative activity, and functional recovery after injury to the central nervous system.

Considerable structural plasticity is possible in the damaged neocortex and connected brain areas, and the potential for significant functional recovery remains even during the chronic phases of the recovery process. In this article, the authors review the literature on use-dependent morphologic events, focusing on the direct interaction of behavioral experience and structural changes associated with plasticity and degeneration. Experience-associated neural changes have the potential to either hinder or enhance functional recovery; therefore, issues concerning the nature, timing, and intensity of behavior-based intervention strategies are addressed.

CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury.

We have reviewed a battery of useful tests for evaluating sensorimotor function and plasticity acutely and chronically in unilateral rat models of central nervous system injury. These tests include forelimb use for weight shifting during vertical exploration in a cylindrical enclosure, an adhesive removal test of sensory function, and forelimb placing. These tests monitor recovery of sensorimotor function independent of the extent of test experience. Data are presented for four models, including permanent focal ischemia, focal injury to the forelimb area of sensorimotor cortex, dopaminergic neurodegeneration of the nigrostriatal system, and cervical spinal cord injury. The effect of the dendrite growth promoting factor, Osteogenic Protein-1 (OP-1) on outcome following permanent middle cerebral artery (MCA) occlusion was used as an example to illustrate how the tests can be applied preclinically. OP-1 showed a beneficial effect on limb use asymmetry in the cylinder test.