Plos One
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Since accumulating evidence suggests the application of anesthetics may increase the risk of Alzheimer's disease (AD), we investigated the cytotoxicity of inhaled general anesthesia in neurons and its underlying mechanism. Using primary cultured rat hippocampal neurons as the study model, here we show that isoflurane increases vulnerability to intracellular or extracellular amyloid β with or without serum deprivation. ⋯ We conclude that isoflurane increases cell death in the presence of amyloid β by increasing Bax level through downregulating miR-214. Our data provide a new insight for inhaled anesthetics toxicity and indicate a possible mechanistic link between anesthetic application and neurodegenration in AD.
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Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM). rTM has been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan, and is currently undergoing a phase III clinical trial in the United States. ⋯ Extracellular histones cause massive thromboembolism associated with consumptive coagulopathy, which is diagnostically indistinguishable from DIC. rTM binds to histones and neutralizes the prothrombotic action of histones. This may contribute to the effectiveness of rTM against DIC.
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Over-activation of the signal transducers and activators of the transcription 3 (Stat3) pathway in lung alveolar type II (AT II) epithelial cells induces chronic inflammation and adenocarcinoma in the lung of CCSP-rtTA/(tetO)7-CMV-Stat3C bitransgenic mice. One of Stat3 downstream genes products, chitinase 3-like 1 (CHI3L1) protein, showed increased concentration in both bronchioalveolar lavage fluid (BALF) and blood of doxycycline-treated CCSP-rtTA/(tetO)7-CMV-Stat3C bitransgenic mice. When tested in other inflammation-induced lung cancer mouse models, the CHI3L1 protein concentration was also highly increased in BALF and blood of these models with tumors. ⋯ Therefore, secretory CHI3L1 plays an important role in inflammation-induced lung cancer formation and potentially serve as a biomarker for lung cancer prediction. Based on our previous publication and this work, this is the first animal study linking overexpression of CHI3L1 to various lung tumor mouse models. These models will facilitate identification of additional biomarkers to predict and verify lung cancer under various pathogenic conditions, which normally cannot be done in humans.
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Exercise training is widely used for neurorehabilitation of Parkinson's disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). ⋯ Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases in rCBF in the medial prefrontal cortex (cingulate, prelimbic, infralimbic). Our results in this PD rat model uniquely highlight the breadth of functional reorganizations in motor and limbic circuits following lesion and long-term, aerobic exercise, and provide a framework for understanding the neural substrates underlying exercise-based neurorehabilitation.
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Recent evidence has supported the neuroprotective effect of bpV (pic), an inhibitor of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in models of ischemic stroke. However, whether PTEN inhibitors improve long-term functional recovery after traumatic brain injury (TBI) and whether PTEN affects blood brain barrier (BBB) permeability need further elucidation. The present study was performed to address these issues. ⋯ These data suggest that treatment with the PTEN inhibitor bpV (pic) has a neuroprotective effect in TBI rats.