Altered resting-state functional connectivity between subregions in the thalamus and cortex in migraine without aura.

BACKGROUND AND PURPOSE: Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes. METHODS: A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed-based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions. RESULTS: The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R-IPL) and right middle frontal gyrus. Furthermore, the FC Z-scores between the VPN and R-IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z-scores between the VPN and R-IPL. CONCLUSION: These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R-IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity.

Hyperbaric oxygen reduces inflammatory response in acute pancreatitis by inhibiting NF-kappaB activation.

AIM: The mechanism of hyperbaric oxygen (HBO) therapy for acute pancreatitis has not been fully clarified yet. The main purpose of this study was to investigate the effect of HBO on nuclear factor kappaB (NF-kappaB) activation and the inflammatory response in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 120 male Sprague-Dawley rats were randomly divided into 3 groups (40 in each): control, ANP and ANP + HBO. ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. HBO treatment was performed at 2.5-fold absolute atmospheric pressure in 90% oxygen for 1, 3, 5, and 7 h. The activation of NF-kappaB and its inhibitor IkappaBalpha in peripheral blood neutrophilic granulocytes was measured by electrophoretic mobility shift assay and Western blot, respectively. The inflammatory cytokines [interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule 1] in the blood were measured by enzyme-linked immunosorbent assay. RESULTS: The blood levels of inflammatory cytokines and NF-kappaB activation were significantly increased in ANP rats compared to control rats, but IkappaBalpha activation was suppressed. The levels of the elevated inflammatory cytokines were positively correlated with the changes in NF-kappaB activation. After HBO treatment, the blood levels of inflammatory cytokines and NF-kappaB activation were significantly decreased in the ANP + HBO group in a time-dependent manner, but IkappaBalpha activation was increased. CONCLUSION: Our findings suggest that acute pancreatitis is associated with the upregulation of cytokines in blood as well as upregulation of NF-kappaB levels and downregulation of IkappaBalpha activation in peripheral blood neutrophilic granulocytes. In contrast, HBO plays a role in acute pancreatitis treatment by normalizing these changes.

Effects of 1,3-dichloropropene on the kidney of Fisher 344 rats after pretreatment with diethyl maleate, buthionine sulfoximine, and aminooxyacetic acid.

Acute nephrotoxicity of cis/trans-1,3-dichloropropene (DCP) was assessed in male Fisher 344 rats. Pretreatment of rats with corn oil, aminooxyacetic acid (AOA), buthionine sulfoximine (BSO), or diethyl maleate (DEM) was given intraperitoneally 1 h or 4 h prior to injection of DCP. Doses of DCP were 0, 25, 50, and 75 mg/kg intraperitoneally (4-5 animals per dose/pretreatment group). Urine was collected for 24 h. Excretion of creatinine, phosphorus, protein, N-acetylglucosaminidase (NAG), and the major metabolite of DCP, N-acetyl-S-(cis-3-chloroprop-2-enyl)-cysteine (3CNAC), was measured. Excretion of the metabolite, 3CNAC, increased in a dose-related manner from 0 to 50 mg/kg of DCP, but further increases were not seen at the 75 mg/kg dose. The pretreatments produced no alterations in the amounts of metabolite excreted when compared to corn oil controls. Zero-order metabolism or impaired metabolism is suggested to be occurring at high doses of DCP. The AOA pretreatment group showed no increase in the excretion of NAG, whereas other pretreatments (corn oil, BSO, DEM) showed elevations of NAG excretion at the highest DCP doses. AOA inhibits renal beta-lyase, an enzyme that mediates cleavage of mercapturic acid metabolites to toxic products. Since NAG excretion was not elevated in response to DCP with AOA pretreatment and was not raised by pretreatments that deplete glutathione, it is suggested that nephrotoxic effects of DCP may be mediated through the mercapturic acid metabolites on the kidney, rather than due to glutathione depletion per se.