Experimental neurology
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Experimental neurology · Jan 2007
Smad3 null mice display more rapid wound closure and reduced scar formation after a stab wound to the cerebral cortex.
Following central nervous system injury, adult mammalian neurons do not regenerate through regions of scar formation. This regenerative failure is due in part to the inhibitory environment of the glial scar at the lesion site. Following injury, transforming growth factor beta (TGF-beta) is strongly induced and is important to many aspects of the response to injury, including deposition of extracellular matrix (ECM) in the glial scar. ⋯ Injury-induced cell proliferation was significantly lower in Smad3 null mice around the lesion. There was no overall difference between wild-type and Smad3 null mice in immunoreactivity for TGF-beta(1) after injury. Thus, our experiments suggest that TGF-beta signaling through Smad3 contributes significantly to the immune response and scar formation after cortical stab wound injury, delaying recovery through multiple mechanisms.
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Experimental neurology · Jan 2007
Late effects of enriched environment (EE) plus multimodal early onset stimulation (MEOS) after traumatic brain injury in rats: Ongoing improvement of neuromotor function despite sustained volume of the CNS lesion.
Recently we showed that the combination between MEOS and EE applied to rats for 7-15 days after traumatic brain injury (TBI) was associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction. In a continuation of this work, we tested whether these effects persisted for longer post-operative periods, e.g. 30 days post-injury (dpi). Rats were subjected to lateral fluid percussion (LFP) or to sham injury. ⋯ We found (i) no differences in the vibrissal motor performance; (ii) EE+MEOS rats performed significantly better than SH rats in NS; (iii) EE-only and EE+MEOS animals, but not SH rats, showed better recovery at 30 dpi than at 15 dpi; (iv) no differences among all groups in CLV (larger than that at 15 dpi) and CLV-RAP, despite a clear tendency to reduction in the EE-only and EE+MEOS rats. We conclude that EE+MEOS retards, but cannot prevent the increase of lesion volume. This retardation is sufficient for a continuous restoration of neurological functions.
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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.