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Nerve Trauma (nerve + trauma)
Selected AbstractsSerum or target deprivation-induced neuronal death causes oxidative neuronal accumulation of Zn2+ and loss of NAD+EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Christian T. Sheline Abstract Trophic deprivation-mediated neuronal death is important during development, after acute brain or nerve trauma, and in neurodegeneration. Serum deprivation (SD) approximates trophic deprivation in vitro, and an in vivo model is provided by neuronal death in the mouse dorsal lateral geniculate nucleus (LGNd) after ablation of the visual cortex (VCA). Oxidant-induced intracellular Zn2+ release ([Zn2+]i) from metallothionein-3 (MT-III), mitochondria or ,protein Zn2+', was implicated in trophic deprivation neurotoxicity. We have previously shown that neurotoxicity of extracellular Zn2+ required entry, increased [Zn2+]i, and reduction of NAD+ and ATP levels causing inhibition of glycolysis and cellular metabolism. Exogenous NAD+ and sirtuin inhibition attenuated Zn2+ neurotoxicity. Here we show that: (1) Zn2+ is released intracellularly after oxidant and SD injuries, and that sensitivity to these injuries is proportional to neuronal Zn2+ content; (2) NAD+ loss is involved , restoration of NAD+ using exogenous NAD+, pyruvate or nicotinamide attenuated these injuries, and potentiation of NAD+ loss potentiated injury; (3) neurons from genetically modified mouse strains which reduce intracellular Zn2+ content (MT-III knockout), reduce NAD+ catabolism (PARP-1 knockout) or increase expression of an NAD+ synthetic enzyme (Wlds) each had attenuated SD and oxidant neurotoxicities; (4) sirtuin inhibitors attenuated and sirtuin activators potentiated these neurotoxicities; (5) visual cortex ablation (VCA) induces Zn2+ staining and death only in ipsilateral LGNd neurons, and a 1 mg/kg Zn2+ diet attenuated injury; and finally (6) NAD+ synthesis and levels are involved given that LGNd neuronal death after VCA was dramatically reduced in Wlds animals, and by intraperitoneal pyr vate or nicotinamide. Zn2+ toxicity is involved in serum and trophic deprivation-induced neuronal death. [source] Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: Effects of brain-derived neurotrophic factor and fibroblast growth factorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2007Josef M. Miller Abstract The extent to which neurotrophic factors are able to not only rescue the auditory nerve from deafferentation-induced degeneration but also promote process regrowth is of basic and clinical interest, as regrowth may enhance the therapeutic efficacy of cochlear prostheses. The use of neurotrophic factors is also relevant to interventions to promote regrowth and repair at other sites of nerve trauma. Therefore, auditory nerve survival and peripheral process regrowth were assessed in the guinea pig cochlea following chronic infusion of BDNF + FGF1 into scala tympani, with treatment initiated 4 days, 3 weeks, or 6 weeks after deafferentation from deafening. Survival of auditory nerve somata (spiral ganglion neurons) was assessed from midmodiolar sections. Peripheral process regrowth was assessed using pan-Trk immunostaining to selectively label afferent fibers. Significantly enhanced survival was seen in each of the treatment groups compared to controls receiving artificial perilymph. A large increase in peripheral processes was found with BDNF + FGF1 treatment after a 3-week delay compared to the artificial perilymph controls and a smaller enhancement after a 6-week delay. Neurotrophic factor treatment therefore has the potential to improve the benefits of cochlear implants by maintaining a larger excitable population of neurons and inducing neural regrowth. © 2007 Wiley-Liss, Inc. [source] Methylprednisolone exacerbates axonal loss following optic nerve trauma in ratsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2002KD Steinsapir PURPOSE: This study investigates the clinical dogma that very high doses of methylprednisolone helpful in spinal cord injury are also helpful in optic nerve trauma. Methods: The right optic nerve of 29 male rats received a 5 second traumatic crush followed 30 minutes later by one of five intravenous treatments (methylprednisolone 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, or saline). Treatment was continued for three additional administrations at 6 hour intervals. Untreated sham controls (n = 7) were also prepared. Six weeks after injury, animals were sacrificed, perfused and optic nerves systematically counted. RESULTS: Axon counts (means +/, s.e.m.) were as follows: Saline = 16,670 +/, 8,900 (n = 5); Methylprednisolone: 30 mg/kg = 8,098 +/, 4,741 (n = 5); 60 mg/kg = 6,925 +/, 6,517 (n = 4); 90 mg/kg = 2,663 +/, 2,653 (n = 4); 120 mg/kg = 6,149 +/, 3,487 (n = 6). Consequently, the data revealed that saline treated animals retained more axons than those that were administered methylprednisolone (p < 0.02). CONCLUSIONS: We conclude that methylprednisolone exacerbates axonal loss following crush injury in the rat optic nerve. Based on the results of this study, clinical studies of traumatic optic neuropathy in the future should also examine the possibility that corticosteroid treatment may have an adverse effect on visual outcome following optic nerve trauma. [source] Persistent Pain After Breast Cancer SurgeryPAIN MEDICINE, Issue 7 2007B Lau Purpose of the study:, To identify strengths and weaknesses in current studies with a view to carrying out a major multi-center study in Australia. Methods:, The literature was reviewed using standard Medline and Ovid methods. Bibliography of well known key recent papers were used to identify further papers. Results:, Studies evaluating persistent pain after breast cancer surgery have been small and few were prospective controlled studies with adequate power. Like Jung et al[1] we found that the literature was inconsistent in defining chronic pain and differentiating the breast cancer surgery pain syndromes. Marked variations in prior studies are due to differences in: study size (n = 22 to 282 patients), methodology, diagnostic criteria, pain assessment instruments, and distribution of demographic and clinical characteristics in the samples studied. Unfortunately the largest study to date, the ALMANAC Trial (n = 1031) which compared sentinel node biopsy vs "standard axillary dissection" evaluated arm and shoulder function and quality of life, but not pain[2]. From the current literature, it appears that neuropathic breast and arm pain are most common. Widely varying prevalence estimates of different neuropathic pain syndromes have been reported: phantom breast pain (3,44%); intercostobrachial neuralgia (ICBN) (16,39%); ICBN in breast conserving surgery (14,61%); and "neuroma pain" (23,49%). The most established risk factors for surgically related neuropathic pain syndromes are intraoperative nerve trauma, severe acute postoperative pain, and high use of postoperative analgesics[1]. Psychosocial distress is reported to be a risk factor and a consequence of chronic pain[1]. Conclusions:, Well-designed large multi-center studies are required to identify prevalences of various pain types, associated risk factors and treatment success for pain after breast cancer surgery. Such a study is in progress through the collaboration of our group with the Sentinel Node vs Axillary Clearance (SNAC) Study of 1000 women following breast surgery, conducted by the Royal Australian College of Surgeons (RACS). [source] The effect of ginkgo biloba on the rat retinal ganglion cell survival in the optic nerve crush modelACTA OPHTHALMOLOGICA, Issue 5 2010Ke Ma Abstract. Purpose:, To investigate the effect of ginkgo biloba on the retinal ganglion cell survival in a rat optic nerve crush model. Methods:, Twenty-four Sprague,Dawley rats were divided randomly into a study group of 12 animals receiving intraperitoneal injections of ginkgo biloba and a control group of 12 animals receiving intraperitoneal saline injections. All injections were performed 1 hr before the optic nerve crush and daily afterwards. For each animal, the right optic nerve was crushed closely behind the globe for 60 seconds using a microclip with 40 g power. The left optic nerve was kept intact. At 23 days after the optic nerve crush, the retinal ganglion cells were labelled retrogradely by injecting 3% fluorogold into both sides of the superior colliculus of the brain. At 4 weeks after the optic nerve crush, the animals were killed. Photographs taken from retinal flat mounts were assessed for the number and density of the retinal ganglion cells. Results:, The survival rate, defined as the ratio of the retinal ganglion cell density in the right eye with the optic nerve crush divided by the retinal ganglion cell density in left eye without an optic nerve trauma, was significantly (p = 0.035) higher in the study group with ginkgo biloba than in the control group (60.0 ± 6.0% versus 53.5 ± 8.0%). Conclusion:, The results suggest that intraperitoneal injections of a ginkgo biloba extract given prior to and daily after an experimental and standardized optic nerve crush in rats were associated with a higher survival rate of retinal ganglion cells. [source] | |||||||||||||