Experimental neurology
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Experimental neurology · Jan 2013
Improved outcome after spinal cord compression injury in mice treated with docosahexaenoic acid.
In this study we have characterised the locomotor recovery, and temporal profile of cell loss, in a novel thoracic compression spinal cord injury (SCI) in the mouse. We have also shown that treatment with docosahexaenoic acid (DHA) is neuroprotective in this model of SCI, strengthening the growing literature demonstrating that omega-3 polyunsaturated fatty acids are neuroprotective after SCI. Compression SCI in C57BL/6 mice was produced by placing a 10 g weight for 5 min onto a 2 mm × 1.5 mm platform applied to the dura at vertebral level T12. ⋯ Mice that received an intravenous (i.v.) injection of 500 nmol/kg DHA 30 min after SCI, showed improved locomotor recovery and, at 28 day survival, reduced neuronal, oligodendrocyte and neurofilament loss, and reduced microglia/macrophage activation. For some of these indices of SCI, enrichment of the diet with 400 mg/kg/day DHA led to further improvement. However, dietary DHA supplementation, without the initial i.v. injection, was ineffective.
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Experimental neurology · Jan 2013
Neuroprotective effect of Pycnogenol® following traumatic brain injury.
Traumatic brain injury (TBI) involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Oxidative stress is one of the most celebrated secondary injury mechanisms. A close relationship exists between levels of oxidative stress and the pathogenesis of TBI. ⋯ Although levels of the proinflammatory cytokines were significantly elevated in both injury groups, the cohort treated with PYC showed a significant reduction compared to vehicle treated controls. These results are the first to show a neuroprotective effect of PYC following TBI. They also suggest that the diverse effects of bioflavonoids may provide a unique avenue for possible therapeutic intervention following head trauma.
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Experimental neurology · Jan 2013
Moderate traumatic brain injury promotes neural precursor proliferation without increasing neurogenesis in the adult hippocampus.
Traumatic brain injury (TBI) promotes neural stem/progenitor cell (NSC) proliferation in the adult hippocampus; however, it remains inconclusive whether proliferation of these cells results in newly generated mature neurons, leading to increased neurogenesis. When we traced the fates of proliferating cells labeled with bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) we found that the number of BrdU-positive cells increased in the hippocampus of TBI mice compared to the sham control. However, double immunostaining to distinguish their cell types showed that most of these cells were glia, and that only a small subpopulation is newborn granular neurons. ⋯ The neurogenesis is not increased by TBI. These data suggest that TBI activates through promotion of NSC proliferation an innate repair and/or plasticity mechanism in the brain. However, additional intervention is required to increase neurogenesis for successfully repairing the damaged brain following TBI.
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Experimental neurology · Jan 2013
Involvement of PKA-dependent upregulation of nNOS-CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats.
We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. ⋯ Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia.
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Experimental neurology · Jan 2013
Human Stiff person syndrome IgG-containing high-titer anti-GAD65 autoantibodies induce motor dysfunction in rats.
Stiff person syndrome (SPS) is an autoimmune CNS disorder characterized by muscle rigidity, spasms and anxiety. The majority of patients have high-titer autoantibodies (ab) against glutamate decarboxylase (GAD65). A pathogenic role of SPS-associated IgG with ab against GAD65 has been shown for anxiety-like behavior but not for the core motor signs. ⋯ Rats injected i.th. with SPS-IgG did not present obvious motor symptoms and had a normal synaptic transmission at the spinal level. We conclude that SPS-like motor dysfunction can be induced in rats by passive transfer of IgG from an SPS-patient with high titer of anti-GAD65 ab. GABAergic dysfunction in supraspinal motor pathways rather than in the spinal cord may lead to motor deficits observed in the rats contrasting observations made in SPS with amphiphysin antibodies.