Neurobiology of disease
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Neurobiology of disease · Jul 2014
Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation.
We identified a suitable biomatrix that improved axon regeneration and functional outcome after partial (moderate) and complete (severe) chronic spinal cord injury (SCI) in rat. Five weeks after dorsal thoracic hemisection injury the lesion scar was resected via aspiration and the resulting cavity was filled with different biopolymers such as Matrigel™, alginate-hydrogel and polyethylene glycol 600 (PEG) all of which have not previously been used as sole graft-materials in chronic SCI. Immunohistological staining revealed marked differences between these compounds regarding axon regeneration, invasion/elongation of astrocytes, fibroblasts, endothelial and Schwann cells, revascularization, and collagen deposition. ⋯ The beneficial effects of PEG-implantation into the resection-cavity were accompanied by long-lasting significant locomotor improvement over a period of 8months. Following complete spinal re-transection at the rostral border of the PEG-graft the locomotor recovery was aborted, suggesting a functional role of regenerated axons in the initial locomotor improvement. In conclusion, scar resection and subsequent implantation of PEG into the generated cavity leads to tissue recovery, axon regeneration, myelination and functional improvement that have not been achieved before in severe chronic SCI.
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Neurobiology of disease · Jun 2014
Complement C5a is detrimental to histological and functional locomotor recovery after spinal cord injury in mice.
Based on the studies on the role of complements C3, C1q and factor B, we hypothesized that complement C5a is detrimental to locomotor recovery at the early stage of secondary injury after spinal cord injury (SCI). To test this hypothesis, we investigated the effect of inhibition of complement C5a receptor (C5aR) by using C5aR antagonist PMX53 (C5aRA) and deficiency of complement C5a receptor (C5aR-/- mice) on histological and locomotor recovery after SCI in mice. We demonstrated that the Basso Mouse Scale scores in the mice injected with C5aRA (C5aRA-mice) at 45min before and 24h after SCI and the C5aR-/- mice were markedly higher than those in the mice treated with saline (Saline-mice) and the C5aR+/+ mice respectively between 7 and 28days after SCI. ⋯ In addition, the percentage of microglia/macrophage in C5aRA mice and C5aR-/- mice was significantly lower than those in their corresponding control groups from 1 to 14days after SCI. Furthermore, C5aRA mice and C5aR-/- mice had less GFAP expression in the injured spinal cord epicenter as compared to Saline mice and C5aR+/+ mice at day 28 after SCI. These findings provided evidence that inhibition or deficiency of C5aR could significantly improve histological and functional locomotor recovery after SCI in mice.
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Neurobiology of disease · May 2014
White matter connectivity reflects clinical and cognitive status in Huntington's disease.
To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease. ⋯ We have provided evidence of aberrant connectivity and microstructural integrity in white matter networks in HD. Microstructural changes in the cortico-striatal fibers were associated with cognitive and motor performance in pre-HD, suggesting that changes in axonal integrity provide an early marker for clinically relevant impairment in HD.
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Neurobiology of disease · May 2014
Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice.
Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a knockout (Scn1a(+/-)) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. ⋯ Furthermore, elevated INa density in excitatory pyramidal neurons at P21-24 correlates with age-dependent onset of lethality in F1. Scn1a(+/-) mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution of pyramidal neuron excitability.
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Neurobiology of disease · Apr 2014
High beta activity in the subthalamic nucleus and freezing of gait in Parkinson's disease.
Oscillatory activity in the beta band is increased in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients. Rigidity and bradykinesia are associated with the low-beta component (13-20Hz) but the neurophysiological correlate of freezing of gait in PD has not been ascertained. ⋯ The association between freezing of gait, high-beta STN oscillations and cortico-STN coherence suggests that this oscillatory activity might interfere in the frontal cortex-basal ganglia networks, thereby participating in the pathophysiology of FOG in PD.