Experimental neurology
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Experimental neurology · Dec 2009
Comparative StudyFlavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone.
Muscle degeneration in dystrophic muscle is exacerbated by the endogenous inflammatory response and increased oxidative stress. A key role is played by nuclear factor(NF)-kappaB. We showed that NF-kappaB inhibition through compounds with also antioxidant properties has beneficial effects in mdx mice, the murine model of Duchenne muscular dystrophy (DMD), but these drugs are not available for clinical studies. ⋯ NF-kappaB binding activity was investigated by electrophoresis mobility shift assay. The administration of flavocoxid: (1) ameliorated functional properties in vivo and ex vivo; (2) reduced CK; (3) reduced the expression of oxidative stress markers and of inflammatory mediators; (4) inhibited NF-kappaB and mitogen-activated protein kinases (MAPKs) signal pathways; (5) reduced muscle necrosis and enhanced regeneration. Our results highlight the detrimental effects of oxidative stress and NF-kappaB, MAPKs and COX/5-LOX pathways in the dystrophic process and show that flavocoxid is more effective in mdx mice than methylprednisolone.
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Experimental neurology · Dec 2009
Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.
Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. ⋯ A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method.
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Experimental neurology · Nov 2009
Forelimb locomotor assessment scale (FLAS): novel assessment of forelimb dysfunction after cervical spinal cord injury.
We describe here a novel forelimb locomotor assessment scale (FLAS) that assesses forelimb use during locomotion in rats injured at the cervical level. A quantitative scale was developed that measures movements of shoulder, elbow, and wrist joints, forepaw position and digit placement, forelimb-hindlimb coordination, compensatory behaviors adopted while walking, and balance. Female Sprague-Dawley rats received graded cervical contusions ranging from 200 to 230 ("mild," n=11) and 250-290 kdyn ("moderate," n=13) between C5 and C8. ⋯ Reliability was tested by having seven raters (three internal, four external) from different laboratories, independently and blindly score videos of all rats. The multivariate correlation between all raters, all animals, and all time points ranged from r(2)=0.88-0.96 (p<0.0001), indicating a high inter-rater reliability. Thus, the FLAS is a simple, inexpensive, sensitive, and reliable measure of forelimb function during locomotion following cervical SCI.
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Experimental neurology · Nov 2009
Comparative StudySpatial diversity of blood-brain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: a comparative MRI study.
Inflammation plays a central role in the development of numerous disorders of the central nervous system (CNS) such as multiple sclerosis (MS). For a long time it was assumed that recruitment of macrophages into the CNS and breakdown of the blood-brain barrier (BBB) are closely linked. In the present study we challenge this concept. ⋯ In conclusion, our findings show macrophage infiltration in the CNS during EAE in areas with a closed BBB for humoral factors. This holds true despite the use of a more sensitive MR contrast agent for BBB disruption than Gd-DTPA. Our experimental observations may have implications for disease monitoring in MS patients by MRI which guides treatment decisions.
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Experimental neurology · Nov 2009
Activation of p-38alpha MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury.
In the present study, we examined whether activation of p-38alpha MAPK modulates mechanical allodynia and neuronal hyperexcitability, and if propentofylline (PPF, a glial modulator) modulates specifically localized activated p-38alpha MAPK expression in caudal regions remote from a low thoracic hemisection injury in rats. T13 spinal hemisection produces bilateral mechanical allodynia in hindpaws with evoked (in response to mechanical stimuli) neuronal hyperexcitability in lumbar spinal wide dynamic range (WDR) neurons compared to sham controls. ⋯ Intrathecal application of PPF significantly attenuated the expression of phosphorylated p-38alpha MAPK in superficial dorsal horn neurons (10 mM) and in microglia (1 and 10 mM) in the lumbar spinal cord compared to the hemisection group (p<0.05). In conclusion, our present data demonstrate that activated neuronal and microglial, but not astrocytic, p-38alpha MAPK contributes to the maintenance of neuronal hyperexcitability in caudal regions following spinal cord injury.