Experimental neurology
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Experimental neurology · Dec 2006
Comparative StudyBlocking EphA4 upregulation after spinal cord injury results in enhanced chronic pain.
Spinal cord injury (SCI) is characterized by a total or partial loss of motor and sensory functions due to the inability of neurons to regenerate. This lack of axonal regenerative response has been associated with the induction of inhibitory proteins for regeneration, such as the Eph receptor tyrosine kinases. One member of this family, the EphA4 receptor, coordinates appropriate corticospinal fibers projections during early development and is expressed in spinal commissural interneurons. ⋯ No locomotor recovery was observed in the rats treated with the EphA4-antisense ODN. Interestingly, reducing EphA4 expression increased mechanical allodynia, as observed by the Von Frey test and decreased exploratory locomotor activity. These results indicate that upregulation of EphA4 receptor after trauma may prevent the development of abnormal pain syndromes and could potentially be exploited as a preventive analgesic mediator to chronic neuropathic pain.
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Experimental neurology · Dec 2006
Comparative StudyThe effects of botulinum neurotoxin A induced muscle paresis during a critical period upon muscle and spinal cord development in the rat.
The second postnatal week is a critical period in rat motor development. The expansion of corticospinal innervation coincides with elimination of polyneuronal innervation of muscles, onset of quadrupedal locomotion and refinement of muscle afferent input to the ventral horn. Such developmental events are believed to be activity-dependent. ⋯ However, CTB labelling also revealed significantly increased motor axon terminals in the ventral Renshaw cell region in BTX-treated animals at P31, accompanied by raised expression of cJun in ipsilateral motoneurones. BTX-treated animals showed deficits in ladder walking, and their muscles contained a higher density and significantly more clustering of slow myosin expressing muscle fibres than controls. Temporary reduction in activity did not significantly alter muscle afferent development, but temporary blockade of neuromuscular junctions did affect both muscle and motor axon, in the longer term.
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Experimental neurology · Dec 2006
Comparative StudyGabapentin depresses C-fiber-evoked field potentials in rat spinal dorsal horn only after induction of long-term potentiation.
C-fiber-evoked field potentials in response to electrical stimulation of the sciatic nerve were recorded in the dorsal horn of the rat lumbar spinal cord, and their long-term potentiation (LTP) was induced by high-frequency stimulation applied on the sciatic nerve as a synaptic model of hypersensitivity underlying an increased efficacy of nociceptive transmission. We evaluated the effect of gabapentin on the basal C-fiber-evoked field potentials and their established LTP. Intravenously administered gabapentin (10 and 30 mg/kg, i.v.) reduced the LTP of C-fiber-evoked field potentials in a dose-dependent manner when applied 60 min after establishment of the LTP. ⋯ Thus, gabapentin was effective only in sensitized conditions. By contrast, morphine HCl (1 and 3 or 10 mg/kg, i.v.) reduced both the basal responses and their established LTP. The combination of gabapentin and morphine at lower doses of each drug appeared to result in a stronger reduction on the established LTP than that of each drug alone, suggesting that combination therapy can generate better analgesia in the treatment of chronic pain.
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Experimental neurology · Dec 2006
Comparative Study2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats.
2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and antiproapoptotic activities. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries might activate a unique signaling pathway, hypoxia-inducible factor-1alpha (HIF-1alpha), to produce or enhance cerebral vasospasm after subarachnoid hemorrhage (SAH). ⋯ Thick blood clot was observed around basilar artery under arachnoids in all animals except Sham group; severe morphological vasospasm was observed in basilar arteries in SAH and SAH+DMSO rats, and the mild vasospasm in rats treated with 2ME2 and D609; 2ME2 and D609 reduced the activity of HIF-1alpha in the basilar arteries by HIF-1alpha DuoSet ELISA; reduce the expression of HIF-1alpha, VEGF, BNIP3 and PCNA in basilar arteries by Western blotting and immunohistochemical staining. In addition, it decreased the mortality and improved the neurological deficits. In conclusion, 2ME2 is a powerful agent to reduce cerebral vasospasm by inhibiting HIF-1alpha activity and the expression of VEGF as its downstream, suppressing endothelium and VSMCs apoptosis via BNIP3 pathway, and attenuating vasoproliferation.