Brain-dependent movements and cerebral-spinal connections: Key targets of cellular and behavioral enrichment in CNS injury models

Abstract

Abstract-One of the most difficult problems in experimental and clinical neurology is how to facilitate recovery of the ability to walk voluntarily. Local spinal mechanisms, descending input from the brain, and ascending sensory feedback to the brain are required for non-treadmill, self-initiated stepping. In evaluating the integrity of axons connecting the brain and spinal cord in neural injury models, the selection of behavioral tests may be at least as important as the histological procedures, if not more so. A comprehensive and clinically meaningful test battery should include assessments of brain-dependent movement capacity. Behavioral enrichment procedures that prominently encourage self-initiation of stepping have been used to facilitate plasticity and motor function after brain or spinal cord injury. Progressive degeneration characteristic of parkinsonian models can be slowed or halted altogether by forced exercise and limb use. Behavioral interventions may work partly because the animal adopts alternative behavioral strategies to compensate for impaired performance. However, mounting evidence suggests that motor rehabilitation can also promote restoration of function or prevent slow degeneration of tissue by engaging constitutively available mechanisms that protect, repair, rewire, or reactivate cells.

Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation

“…Our pilot study adds to the modest literature in humans and the large literature in animals (Schallert and Woodlee, 2003), suggesting that behavioral enrichment procedures that prominently encourage self-initiation of stepping will facilitate plasticity and motor function after brain or spinal cord injury. Specific mechanisms of action for such adaptations may include modulation of Hebbian plasticity and induction of long-term potentiation at a molecular and morphological level, such as neuronal cell precursor proliferation and migration, growth and retraction of dendritic spines, production of neurotrophins, and other biological responses to motor learning (Biernaskie et al, 2004;Cramer and Chopp, 2000;Frost et al, 2003;Gomez-Pinilla et al, 2002;Johansson and Belichenko, 2002;Kleim et al, 2002;Lotze et al, 2003a;Morgen et al, 2004;Rossini et al, 2003;Schaechter and Cramer, 2003;Uy et al, 2003;van Praag et al, 1999).…”

“…Thus, the CPG requires supraspinal input for even simple locomotion on flat surfaces. During normal quadrupedal walking, direct corticospinal projections to the lumbosacral alpha-motoneuron and interneuron pools, along with spinal inputs from brainstem locomotor regions, seg-mental lumbosacral afferents, and local spinal mechanisms aid in the initiation, maintenance, and coordination of rhythmic stepping (Pearson, 2000;Schallert and Woodlee, 2003). The specific role of spinal organization and reorganization for walking after stroke requires further study in animal models and physiological studies in patients.…”

Behavioral tests for preclinical intervention assessment

“…7,[25][26][27] The animal is held aloft with all four limbs hanging freely. With minimal training the animal relaxes and when the vibrissae on one side contact the table corner, the limb on the same side readily moves forward to gain weight support.…”

Intracerebral Hemorrhage in the Iron-Deficient Rat

“…Injury to BG or related sensorimotor tracks results in forelimb deficits contralateral to the injury. 11,13,14 Vibrassae-stimulated forelimb placing was assessed by 10 trials for each forelimb and expressed as a percentage [right (injured BG side)Ϫleft (noninjured BG side)]. Forelimb use asymmetry was assessed by videotaping animals exploring a 20ϫ30 cm plastic cylinder until 20 forelimb placements were observed.…”