Experimental neurology
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Experimental neurology · Dec 2000
Plasticity in the rat spinal cord seen in response to lesions to the motor cortex during development but not to lesions in maturity.
Motor cortical inputs and proprioreceptive muscle afferents largely target the same spinal cord region. This study explored the idea that during development the two inputs interact via an activity-dependent mechanism to produce mature patterns of innervation. In rats, the forelimb motor cortex was ablated unilaterally at either postnatal day 7 (P7), the beginning of corticospinal synaptogenesis in the cervical cord, or at P50. ⋯ Also, the ratio of parvalbumin-positive neurons contralateral/ipsilateral to the developmental lesion (but not adult lesions) was decreased and the ratio of cJun-positive motoneurons increased. Thus, an early motor cortex lesion resulted in retention of a proportion of muscle afferent synapses to the ventral horn that are known to be lost during normal development. Parvalbumin and cJun are markers of neuronal activity suggesting that spinal circuitry develops permanently altered activity patterns in response to an early cortical lesion, although this plasticity is lost in the mature animal.
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Experimental neurology · Dec 2000
Functional MRI at 4.7 tesla of the rat brain during electric stimulation of forepaw, hindpaw, or tail in single- and multislice experiments.
Stimulation of peripheral nerves activates corresponding regions in sensorimotor cortex. We have applied functional magnetic resonance imaging (fMRI) techniques to monitor activated brain regions by means of measuring changes of blood oxygenation level-dependent contrast during electric stimulation of the forepaw, hindpaw, or tail in rats. During alpha-chloralose anesthesia, artificial respiration, and complete muscle relaxation, stimulations were delivered at 3 Hz via subcutaneous bipolar electrodes with 500-microseconds-current pulses of 0.2-2.0 mA. ⋯ Tail stimulation gave rise to a strikingly extended bilateral cortical activation, localized along the midline in medial parietal and frontal cortex 4 and 5 mm posterior to the rhinal fissure. In conclusion, the experiments provide evidence that peripheral nerve stimulation induces a fMRI signal in the respective division of the somatosensory cortex in a stimulus-related manner. The marked cortical activation elicited by tail stimulation underlines the key importance of the tail.
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Experimental neurology · Nov 2000
Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment.
The inflammatory response that ensues during the initial 48 to 72 h after spinal cord injury causes considerable secondary damage to neurons and glia. Infiltration of proinflammatory-activated neutrophils and monocytes/macrophages into the cord contributes to spinal cord injury-associated secondary damage. beta2 integrins play an essential role in leukocyte trafficking and activation and arbitrate cell-cell interactions during inflammation. The beta2 integrin, alphaDbeta2, is expressed on monocytes/macrophages and neutrophils and binds to vascular adhesion molecule-1 (VCAM-1). ⋯ At a 1 mg/kg dose two of three anti-alphaD mAbs caused a significant ( approximately 65%) reduction in the number of macrophages at the injury site and one anti-alphaD mAb led to a approximately 43% reduction in the number of neutrophils at the SCI site. Thus, our results support the concept that the alphaDbeta2 integrins play an important role in the trafficking of leukocytes to a site of central nervous system inflammation. This study also offers preliminary evidence that anti-alphaD mAbs can reduce the extravasation of macrophages and, to a lesser extent, neutrophils, to the SCI site.
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Experimental neurology · Nov 2000
Postinjury administration of L-deprenyl improves cognitive function and enhances neuroplasticity after traumatic brain injury.
The rat model of combined central fluid percussion traumatic brain injury (TBI) and bilateral entorhinal cortical lesion (BEC) produces profound, persistent cognitive deficits, sequelae associated with human TBI. In contrast to percussive TBI alone, this combined injury induces maladaptive hippocampal plasticity. Recent reports suggest a potential role for dopamine in CNS plasticity after trauma. ⋯ AChE histostaining in CA3 was significantly elevated with l-deprenyl in both injury models. After TBI + BEC, l-deprenyl also increased AChE in the dentate molecular layer relative to untreated injured cases. These results suggest that dopaminergic/noradrenergic enhancement facilitates cognitive recovery after brain injury and that noradrenergic fiber integrity is correlated with enhanced synaptic plasticity in the injured hippocampus.
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Experimental neurology · Oct 2000
Sensitivity of NGF-responsive dorsal root ganglion neurons to semaphorin D is maintained in both neonatal and adult mice.
Using a coculture assay of DRG neurons and aggregates of cells transfected with individual semaphorins, we have investigated the ability of semaphorins A, D, and E to inhibit axonal growth from DRG neurons. We show that axons of these neurons that grow in response to NGF remain responsive to semaphorin D in neonatal and in adult mice, although sensitivity may decline in the latter. Consistent with these findings, expression of the semaphorin receptor, neuropilin-1, is maintained in the DRGs of adult mice.