Journal of neurochemistry
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Journal of neurochemistry · Jun 2007
Mitochondrial dysfunction early after traumatic brain injury in immature rats.
Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI. ⋯ Four hours after TBI, pyruvate dehydrogenase complex activity and cytochrome c content (ipsilateral/contralateral ratios) were lower in TBI mitochondria. These data demonstrate abnormal mitochondrial function early (
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Journal of neurochemistry · May 2007
IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro.
It has been shown that Abeta inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1beta. Abeta also increases microglial activation, which is the likely cell source of IL-1beta. Because IL-4 attenuates the effects of IL-1beta in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Abeta on LTP and IL-1beta concentration. ⋯ We report that the Abeta-induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL-1beta concentration, and that these changes were attenuated by treatment of rats with IL-4 and minocycline. We also report that Abeta-induced increases in expression of MHCII and IL-1beta were similarly attenuated by IL-4 and minocycline in glial cultures prepared from neonatal rats. These data suggest that glial cell activation and the consequent increase in IL-1beta concentration mediate the inhibitory effect of Abeta on LTP and indicate that IL-4, by down-regulating glial cell activation, antagonizes the effects of Abeta.
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Journal of neurochemistry · Apr 2007
Post-trauma Lipitor treatment prevents endothelial dysfunction, facilitates neuroprotection, and promotes locomotor recovery following spinal cord injury.
We have previously reported neuroprotection in spinal cord injury (SCI) by Lipitor [atorvastatin (AT)]-pre-treatment. Though informative, pre-treatment studies find only limited clinical application as trauma occurrence is unpredictable. Therefore, this study investigates the efficacy of AT treatment post-SCI. ⋯ Attenuation of these early inflammatory events reduced secondary damage. Significant reduction in axonal degeneration, myelin degradation, gliosis, and neuronal apoptosis with resultant enhancement in tissue sparing was observed in AT-SCI compared with VHC-SCI. In summary, this novel report presenting the efficacy of post-injury AT treatment might be of critical therapeutic value as effective treatments are currently unavailable for SCI.
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Journal of neurochemistry · Apr 2007
Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents.
Thiazolidinediones (TZDs) are synthetic agonists of the ligand-activated transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma). TZDs are known to curtail inflammation associated with peripheral organ ischemia. As inflammation precipitates the neuronal death after stroke, we tested the efficacy of TZDs in preventing brain damage following transient middle cerebral artery occlusion (MCAO) in adult rodents. ⋯ Rosiglitazone treatment curtailed the post-ischemic expression of the pro-inflammatory genes interleukin-1beta, interleukin-6, macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, cyclooxygenase-2, inducible nitric oxide synthase, early growth response-1, CCAAT/enhancer binding protein-beta and nuclear factor-kappa B, and increased the expression of the anti-oxidant enzymes catalase and copper/zinc-superoxide dismutase. Rosiglitazone also increased the expression of the anti-inflammatory gene suppressor of cytokine signaling-3 and prevented the phosphorylation of the transcription factor signal transducer and activator of transcription-3 after focal ischemia. Thus, PPARgamma activation with TZDs might be a potent therapeutic option for preventing inflammation and neuronal damage after stroke with promise in diabetic and hypertensive subjects.
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Journal of neurochemistry · Apr 2007
Axonal involvement in the Wlds neuroprotective effect: analysis of pure motoneurons in a mouse model protected from motor neuron disease at a pre-symptomatic age.
The identification of the Wlds gene that delays axonal degeneration in several models of neurodegenerative disease provides an interesting tool to study mechanisms of axonal loss. We showed that crossing a mouse mutant with a motoneuron disease (pmn for progressive motor neuronopathy) with mice that express the Wlds gene delayed axonal loss, increased the life span, partially rescued axonal transport deficit and prolonged the survival of the motoneuron cell bodies. To determine factors involved in the neuroprotective effect of Wlds, we combined laser capture microdissection and microarray analysis to identify genes that are differentially regulated at a pre-symptomatic age in motoneuron cell bodies in pmn/pmn,Wlds/Wlds mice as compared with pmn/pmn mice. ⋯ Interestingly, a large proportion of these genes are related to axonal function and to retrograde and anterograde transport (i.e. members of the dynactin complex and kinesin family). These results were confirmed by real-time PCR, in situ hybridization and at protein level in sciatic nerves. Thus, genes related to axonal function and in particular to axonal transport may be involved at an early stage in the neuroprotective property of the Wlds gene and confirm the importance of axonal involvement in this model of motor neuron disease.