Experimental neurology
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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 · Nov 2006
Comparative StudyAlterations in hippocampal neurogenesis following traumatic brain injury in mice.
Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dcx) up to 14 days after TBI. ⋯ No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impairment.
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Experimental neurology · Nov 2006
Comparative StudyLocal and distal responses to injury in the rapid functional recovery from spinal cord contusion in rat pups.
Young rats display an accelerated rate of locomotor recovery after contusive spinal cord injury (SCI) compared to adults subjected to a similar standardized injury. We examined possible differences in the responses to SCI at the injury site and in the distal cord that might contribute to this rapid recovery. P14-15 rats were studied at 1, 3, 5, 7, and 28 days after injury at T8 produced with a weight drop device (10 g x 2.5 cm). ⋯ No evidence of oligodendrocyte loss in spared white matter was detected at 24 h after injury, as compared to the 50% loss reported in adults. Rather, there was a significant increase in the density of oligodendrocytes by 5 days after injury that was associated with a dramatic upregulation of markers for glial progenitor cells after pup SCI. Our results suggest that an altered glial response near the injury epicenter as compared to that in adults is likely to contribute to the more rapid rate of recovery in hindlimb locomotor function in young rats after SCI.
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Experimental neurology · Oct 2006
Contralesional neural plasticity and functional changes in the less-affected forelimb after large and small cortical infarcts in rats.
Some studies have found that unilateral cerebral damage produces significant deficits in the ipsilesional, "less-affected", body side. Other studies have found that such damage results in a paradoxical hyperfunctionality of the ipsilesional body side and a facilitation of learning-induced neuroplastic changes in the contralesional motor cortex. The purpose of this study was to determine whether these effects co-exist and/or vary with lesion severity. ⋯ These effects were correlated with reaching performance. Therefore, enhanced motor skill learning in the "less-affected" forelimb and contralesional neuroplastic changes are muted after larger lesions and co-exist with ipsilesional impairments. These effects may be related to a denervation-induced neural restructuring of the contralesional cortex that both disrupts pre-existing motor engrams and facilitates the establishment of new ones.
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Experimental neurology · Oct 2006
Pain with no gain: allodynia following neural stem cell transplantation in spinal cord injury.
Transplantation of neural stem cells (NSCs) in the injured spinal cord has been shown to improve functional outcome; however, recent evidence has demonstrated forelimb allodynia following transplantation of embryonic NSCs. The aim of this study was to investigate whether transplantation of murine C17.2 NSCs alone or transfected with glial-derived neurotrophic factor (C17.2/GDNF) would induce allodynia in transplanted spinal cord-injured animals. One week after a T8-level spinal cord injury (SCI), C17.2, C17.2/GDNF or normal saline was injected at the injury site. ⋯ Sprouting of nocioceptive afferents occurred rostral to the injury/transplantation site only in allodynic animals, suggesting a principal role in this aberrant pain state. Further, a difference in the degree of allodynia was noted between C17.2- and C17.2/GDNF transplant-treated groups; this difference correlated with the level of CGRP/GAP43 immunoreactivity and sprouting observed in the cervicothoracic dorsal horns. Both allodynia- and CGRP/GAP43-positive afferent sprouting were less in the C17.2/GDNF group compared to the C17.2 group, suggesting a possible protective or analgesic effect of GDNF on post-injury neuropathic pain.