Neocortical localization of tactile/proprioceptive limb placing reactions in the rat

Ryck, March De; Reempts, Jos Van; Duytschaever, Hilde; Deuren, Bruno Van; Clincke, G.

doi:10.1016/0006-8993(92)90112-m

Cited by 87 publications

(57 citation statements)

References 61 publications

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“…Here, the observation period was extended to 4 weeks (compared with 3 weeks in the contusion model) because the lesion was more severe. Since correct foot placing is associated with correct CST function (De Ryck et al, 1992;Metz and Whishaw, 2002), we also analyzed stepping and correct paw positioning scores for the contusion model (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

“…The BMS is a ten-point locomotor rating scale (ranging from 9normal locomotion to 0complete hind-limb paralysis), in which mice are scored by two investigators who were unaware of the experimental groups based on hind-limb movements made in an open field during a 4-minute interval. Since correct foot placing correlates with proper CST function (De Ryck et al, 1992;Metz and Whishaw, 2002) and because subscores for each attribute of the BMS can be used to reveal recovery responses for individual locomotor features (Basso et al, 2006), stepping performance and correct paw positioning were evaluated. The scoring of the stepping was performed to emphasize whether plantar stepping was present in less (score of 0) or more (score of 1) than 50% of the steps, provided the animal was moving at least three body lengths at consistent speed.…”

Section: Locomotion Testsmentioning

confidence: 99%

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C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

Boato

Hendrix

Huelsenbeck

et al. 2010

Journal of Cell Science

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SummaryFunctional recovery and regeneration of corticospinal tract (CST) fibers following spinal cord injury by compression or dorsal hemisection in mice was monitored after application of the enzyme-deficient Clostridium botulinum C3-protein-derived 29-amino-acid fragment C3bot . This peptide significantly improved locomotor restoration in both injury models as assessed by the open-field Basso Mouse Scale for locomotion test and Rotarod treadmill experiments. These data were supported by tracing studies showing an enhanced regenerative growth of CST fibers in treated animals as visualized by anterograde tracing. Additionally, C3bot stimulated regenerative growth of raphespinal fibers and improved serotonergic input to lumbar -motoneurons. These in vivo data were confirmed by in vitro data, showing an enhanced axon outgrowth of -motoneurons and hippocampal neurons cultivated on normal or growth-inhibitory substrates after application of C3bot . The observed effects were probably caused by a non-enzymatic downregulation of active RhoA by the C3 peptide as indicated by pull-down experiments. By contrast, C3bot 154-182 did not induce neurite outgrowth in primary cultures of dorsal root ganglion cells. In conclusion, C3bot154-182 represents a novel, promising tool to foster axonal protection and/or repair, as well as functional recovery after traumatic CNS injury.

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Section: Resultsmentioning

confidence: 99%

Section: Locomotion Testsmentioning

confidence: 99%

C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

Boato

Hendrix

Huelsenbeck

et al. 2010

Journal of Cell Science

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“…Normal animals rapidly place their forelimb on the table top. Performance was scored between 0 (normal) and 10 (maximal impairment) (18,19). Similarly, the hindlimb-placing test evaluated the animal's ability to place the hindpaw on a table in response to light stimulation and was scored on a 0-6 scale.…”

Section: Methodsmentioning

confidence: 99%

Inosine induces axonal rewiring and improves behavioral outcome after stroke

Chen

Goldberg

Kolb

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

240

178

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Cerebral infarct (stroke) often causes devastating and irreversible losses of function, in part because of the brain's limited capacity for anatomical reorganization. The purine nucleoside inosine has previously been shown to induce neurons to express a set of growthassociated proteins and to extend axons in culture and in vivo. We show here that in adult rats with unilateral cortical infarcts, inosine stimulated neurons on the undamaged side of the brain to extend new projections to denervated areas of the midbrain and spinal cord. This growth was paralleled by improved performance on several behavioral measures. C erebral ischemic infarct, or stroke, affects approximately 750,000 people annually in the U.S. alone. Depending on the locus of damage and other complicating factors, stroke can result in devastating losses in sensory, motor, and cognitive functions. A limited amount of synaptic reorganization is thought to occur spontaneously in the brain after stroke (1-5) or focal injury (6, 7) and can be enhanced by training (8, 9). However, there is little evidence that undamaged neurons can extend lengthy projections to reinnervate brain regions that have lost their normal inputs, nor are any clinical methods available to improve functional outcome by stimulating axonal reorganization after stroke.The purine nucleoside inosine enters cells via facilitated diffusion or can be synthesized readily from adenosine. In at least some neurons, inosine activates an intracellular signaling pathway that regulates the expression of multiple genes involved in axon outgrowth (10,11). In vivo, inosine treatment can promote extensive sprouting of the intact corticospinal tract (CST) into areas denervated by transecting the contralateral CST (12). Here, we have investigated whether inosine treatment can stimulate axonal growth and help improve behavioral outcome after stroke. The rat's sensorimotor cortex is required for fine motor control of the contralateral limbs (5,13,14). After creating a stroke that damaged most of the sensorimotor cortex on one side of the brain, we tested whether inosine could induce neurons in the intact hemisphere to grow new connections to denervated target areas and restore cortical control to the hemiparetic side. Although a number of neural pathways may be important in this regard, we have focused on the corticorubral tract and CST, two pathways that help mediate fine motor coordination (15,16). Our results demonstrate that inosine stimulates significant axonal reorganization after stroke and leads to improved performance on several sensorimotor tasks. MethodsSurgery. Male Sprague-Dawley rats (250-325 g, age range 8-10 weeks: Charles River Breeding Laboratories) were used throughout. In a pilot study done in collaboration with Cerebrotec (Boston), we investigated whether inosine treatment would improve behavioral outcome after stroke. Under halothane anesthesia, rats were placed on their sides, and a vertical incision was made midway between the right orbit and external auditory canal. The underly...

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“…Beginning on the day of surgery and continuing every other day for 2 weeks, animals were examined by using a limb placing test to assess sensorimotor function in the forelimb (10,11). Specifically, the forelimb placing test measures sensorimotor function in each forelimb as the animal places the limb on a tabletop in response to visual, tactile, and proprioceptive stimuli (total score ϭ 0-12; 12 ϭ maximally impaired).…”

Section: Methodsmentioning

confidence: 99%

Functional magnetic resonance imaging of reorganization in rat brain after stroke

Dijkhuizen

Ren

Mandeville

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

281

219

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Functional recovery after stroke has been associated with brain plasticity; however, the exact relationship is unknown. We performed behavioral tests, functional MRI, and histology in a rat stroke model to assess the correlation between temporal changes in sensorimotor function, brain activation patterns, cerebral ischemic damage, and cerebrovascular reactivity. Unilateral stroke induced a large ipsilateral infarct and acute dysfunction of the contralateral forelimb, which significantly recovered at later stages. Forelimb impairment was accompanied by loss of stimulusinduced activation in the ipsilesional sensorimotor cortex; however, local tissue and perfusion were only moderately affected and cerebrovascular reactivity was preserved in this area. At 3 days after stroke, extensive activation-induced responses were detected in the contralesional hemisphere. After 14 days, we found reduced involvement of the contralesional hemisphere, and significant responses in the infarction periphery. Our data suggest that limb dysfunction is related to loss of brain activation in the ipsilesional sensorimotor cortex and that restoration of function is associated with biphasic recruitment of peri-and contralesional functional fields in the brain.

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Neocortical localization of tactile/proprioceptive limb placing reactions in the rat

Cited by 87 publications

References 61 publications

C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

Inosine induces axonal rewiring and improves behavioral outcome after stroke

Functional magnetic resonance imaging of reorganization in rat brain after stroke

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