Experimental neurology
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Experimental neurology · Mar 2005
Fibroblast growth factor 2 induces loss of adult oligodendrocytes and myelin in vivo.
Oligodendrocytes are the myelin-forming cells of the CNS and are lost in demyelinating diseases such as multiple sclerosis (MS). A role for fibroblast growth factor 2 (FGF2) has been proposed in the pathogenesis of demyelination and the failure of remyelination in experimental models of MS. However, the in vivo effects of FGF2 on oligodendrocytes and oligodendrocyte progenitors (OPCs) in the adult CNS had not previously been determined. ⋯ At the same time, FGF2 treatment resulted in the aberrant accumulation of immature oligodendrocytes with a premyelinating phenotype, together with NG2-expressing OPCs. Axons are patent within demyelinated lesions, and they are contacted but not ensheathed by surviving oligodendrocytes, newly formed premyelinating oligodendrocytes and OPCs. These results demonstrate that raised FGF2 induces demyelination in the adult CNS, and support a role for FGF2 in the pathogenesis of demyelination and regulation of remyelination in MS.
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Experimental neurology · Mar 2005
Changes in pituitary adenylate cyclase activating polypeptide expression in urinary bladder pathways after spinal cord injury.
These studies examined changes in the pituitary adenylate cyclase activating polypeptide (PACAP) expression in micturition reflex pathways after spinal cord injury (SCI) of various durations. In spinal-intact animals, PACAP immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L1, L2, L4-S1). Bladder-afferent cells (35-45%) in the dorsal root ganglia (DRG; L1, L2, L6, S1) from spinal-intact animals also exhibited PACAP-IR. ⋯ No changes were observed in the L4-L5 DRG. PACAP-IR was reduced throughout the urothelium and detrusor smooth muscle whole mounts after SCI. These studies demonstrate changes in PACAP expression in micturition reflex pathways after SCI that may contribute to urinary bladder dysfunction or reemergence of primitive voiding reflexes after SCI.
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Experimental neurology · Feb 2005
Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat.
A graded contusion spinal cord injury (SCI) was created in the adult rat spinal cord using the Infinite Horizons (IH) impactor to study the correlation between injury severity and anatomical, behavioral, and electrophysiological outcomes. Adult Fisher rats were equally divided into five groups and received contusion injuries at the ninth thoracic level (T9) with 100, 125, 150, 175, or 200 kdyn impact forces, respectively. Transcranial magnetic motor-evoked potentials (tcMMEPs) and BBB open-field locomotor analyses were performed weekly for 4 weeks postinjury. ⋯ Comparison of tcMMEP responses with areas of WM loss or demyelination identified the medial ventrolateral funiculus (VLF) as the location of the tcMMEP pathway. Immunohistochemical and electromicroscopic (EM) analyses showed the presence of demyelinated axons in WM tracts surrounding the lesion cavities at 28 days postinjury. These data support the notion that widespread WM damage in the ventral and lateral funiculi may be a major cause for locomotor deficits and lack of tcMMEP responses after SCI.
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Experimental neurology · Feb 2005
Intrinsic neural circuits between dorsal midbrain neurons that control fear-induced responses and seizure activity and nuclei of the pain inhibitory system elaborating postictal antinociceptive processes: a functional neuroanatomical and neuropharmacological study.
The blockade of GABA-mediated Cl(-) influx with pentylenetetrazol (PTZ) was used in the present work to induce seizures in Rattus norvegicus. The aim of this work was to study the involvement of monoamines in the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. ⋯ The functional neuroanatomical study of the neural link between the mesencephalic tectum and nuclei of the central pain inhibitory system showed evidence for the interconnection between superior colliculus, both dorsal and ventral periaqueductal gray matter (PAG), and inferior colliculus. Defensive substrates of the inferior colliculus, also involved with wild running and epilepsy, send inputs toward dorsal raphe nucleus and locus coeruleus. Since these nuclei are rich in monoamines and send neural connections toward other monoaminergic nuclei of the brainstem involved with the control of the nociceptive inputs in the dorsal horn of the spinal cord, the present results offer a neuroanatomical and psychopharmacological basis for the antinociceptive processes following tonic-clonic seizures.
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Experimental neurology · Feb 2005
Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats.
Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance. While more functional recovery occurs with greater white matter sparing (WMS), it is unclear which locomotor features are more vulnerable to SCI than others, if recovery of certain features depends on specific amounts of WMS, and whether motor recovery patterns differ from sensory recovery. Locomotor and sensory recovery after graded contusive SCI with cord displacements of 0.3, 0.5, 0.7, 0.9, 1.1, 1.25, and 1.3 mm was examined for 6 weeks in 80 female Sprague-Dawley rats. ⋯ Mechanical allodynia developed only after injuries resulting in < or =10% WMS. Nonlinear motor and sensory recovery patterns suggest that small reparative changes may substantially improve function in individuals with SCI. A hierarchical locomotor recovery based on simple segmental versus complex supraspinal motor control is proposed.