Brain research
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Mitochondria critically regulate cytoplasmic Ca(2+) concentration ([Ca(2+)]c), but the effects of sensory neuron injury have not been examined. Using FCCP (1µM) to eliminate mitochondrial Ca(2+) uptake combined with oligomycin (10µM) to prevent ATP depletion, we first identified features of depolarization-induced neuronal [Ca(2+)]c transients that are sensitive to blockade of mitochondrial Ca(2+) buffering in order to assess mitochondrial contributions to [Ca(2+)]c regulation. This established the loss of a shoulder during the recovery of the depolarization (K(+))-induced transient, increased transient peak and area, and elevated shoulder level as evidence of diminished mitochondrial Ca(2+) buffering. ⋯ Whereas application of FCCP plus oligomycin 2s after neuronal depolarization initiated mitochondrial Ca(2+) release in most Control and SNL L4 neurons, this usually failed to release mitochondrial Ca(2+) from SNL L5 neurons. For comparable cytoplasmic Ca(2+) loads, the releasable mitochondrial Ca(2+) in SNL L5 neurons was less than Control while it was increased in SNL L4 neurons. These findings show diminished mitochondrial Ca(2+) buffering in axotomized SNL L5 neurons but enhanced Ca(2+) buffering by neurons in adjacent SNL L4 neurons.
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During the development of sepsis, the complication in central nervous system (CNS), appearing early and frequently relative to other systems, can obviously increase the mortality of sepsis. Moreover, sepsis survivors also accompany long-term cognitive dysfunction, while the ultimate causes and effective therapeutic strategies of brain injury in sepsis are still not fully clear. We designed this study to investigate the effects of 2% hydrogen gas (H2) on brain injury in a mouse model of sepsis. ⋯ Furthermore, we found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis. Thus, the inhalation of hydrogen gas may be a promising therapeutic strategy to relieve brain injury in sepsis.
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Nerve decompression is an important therapeutic strategy to relieve neuropathic pain and promote the peripheral nerve regeneration. To address these issues, we investigated the effects of nerve decompression on relief of neuropathic pain behaviors, redistribution of voltage-gated sodium channels (VGSCs), and skin reinnervation with chronic constriction injury (CCI). At post-operative week (POW) 4, animals were divided into a decompression group, in which the ligatures were removed, and a CCI group, in which the ligatures remained. ⋯ These observations demonstrated that nerve decompression was accompanied with the disappearance of neuropathic pain behaviors after CCI. Morphological studies provided the evidence that redistribution of VGSCs along the injured sciatic nerve but still with an incomplete skin reinnervation. These significant findings demonstrated a role of VGSCs in the pathogenesis of neuropathic pain, and gave an approaching in pharmacological basis of therapeutics.
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Comparative Study
Human brain asymmetry in microstructural connectivity demonstrated by diffusional kurtosis imaging.
Structural asymmetry of whole brain white matter (WM) pathways, i.e., the connectome, has been demonstrated using fiber tractography based on diffusion tensor imaging (DTI). However, DTI-based tractography fails to resolve axonal fiber bundles that intersect within an imaging voxel, and therefore may not fully characterize the extent of asymmetry. The goal of this study was to assess structural asymmetry with tractography based on diffusional kurtosis imaging (DKI), which improves upon DTI-based tractography by delineating intravoxel crossing fibers. ⋯ Rightward asymmetrical ROI and links were observed in superior frontal lobe, cingulate cortex, fusiform, putamen, and medial temporal lobe. Interestingly, these observed structural asymmetries were incompletely identified with DTI-based tractography. These results suggest that DKI-based tractography can improve the identification of asymmetrical connectivity patterns, thereby serving as an additional tool in the evaluation of the structural bases of functional lateralization.
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Stroke is a leading cause of morbidity and mortality in the world. Low-dose methylene blue (MB), which has been used safely to treat methemoglobinemia and cyanide poisoning in humans, has energy enhancing and antioxidant properties. We tested the hypothesis that methylene blue treatment delays progression of at-risk tissue (ca. perfusion-diffusion mismatch) to infarct in permanent middle cerebral artery occlusion in rats at two MB treatment doses. ⋯ The major findings were: (i) MB significantly prolonged the perfusion-diffusion mismatch, (ii) MB mildly increased the CBF in the hypoperfused tissue, (iii) MB did not change the final infarct volume in permanent ischemic stroke, and (iv) there were no dose-dependent effects on mismatch progression for the 1 and 3mg/kg doses studied. This neuroprotective effect is likely the result of sustained ATP production and increased CBF to tissue at risk. This work has the potential to readily lead to clinical stroke trials given MB's excellent safety profile.