In vitro studies have well established the neuroprotective action of the noble gas argon. However, only limited data from in vivo models are available, and particularly whether postexcitotoxic or postischemic argon can provide neuroprotection in vivo still remains to be demonstrated. Here, we investigated the possible neuroprotective effect of postexcitotoxic-postischemic argon both ex vivo in acute brain slices subjected to ischemia in the form of oxygen and glucose deprivation (OGD), and in vivo in rats subjected to an intrastriatal injection of N-methyl-D-aspartate (NMDA) or to the occlusion of middle-cerebral artery (MCAO). We show that postexcitotoxic-postischemic argon reduces OGD-induced cell injury in brain slices, and further reduces NMDA-induced brain damage and MCAO-induced cortical brain damage in rats. Contrasting with its beneficial effect at the cortical level, we show that postischemic argon increases MCAO-induced subcortical brain damage and provides no improvement of neurologic outcome as compared to control animals. These results extend previous data on the neuroprotective action of argon. Particularly, taken together with previous in vivo data that have shown that intraischemic argon has neuroprotective action at both the cortical and subcortical level, our findings on postischemic argon suggest that this noble gas could be administered during but not after ischemia, i.e. before but not after reperfusion has occurred, in order to provide cortical neuroprotection and to avoid increasing subcortical brain damage. Also, the effects of argon are discussed as regards to the oxygen-like chemical, pharmacological, and physical properties of argon.

Background Peripheral irritation-induced sensory plasticity may involve catecholaminergic innervation of sensory neurons in the dorsal root ganglia (DRG). Methods Catecholaminergic fiber outgrowth in the thoracolumbar DRG (T13-L2) was examined by tyrosine hydroxylase (TH) immunostaining, or by sucrosepotassium phosphate-glyoxylic acid histofluorescence method. TH level was examined by Western blot. Colonic afferent neurons were labeled by retrograde neuronal tracing. Colitis was induced by intracolonic instillation of tri-nitrobenzene sulfonic acid (TNBS). Key Results The catecholaminergic fibers formed ‘basket-like’ structures around the DRG cells. At 7 days following TNBS treatment, the number of DRG neurons surrounded by TH-immunoreactive fibers and the protein levels of TH were significantly increased in T13, L1, and L2 DRGs (two- to threefold, P < 0.05). The DRG neurons that were surrounded by TH immunoreactivity were 200 kDa neurofilament-positive, but not isolectin IB4-positve or calcitonin gene-related peptide-positive. The TH-immunoreactive fibers did not surround but adjoin the specifically labeled colonic afferent neurons, and was co-localized with glial marker S-100. Comparison of the level of TH and the severity of colonic inflammation showed that following TNBS treatment, the degree of colonic inflammation was most severe at day 3, subsided at day 7, and significantly recovered by day 21. However, the levels of TH in T13-L2 DRGs were increased at both 3 days and 7 days post TNBS treatment and persisted up to 21 days (two- to fivefold increase, P < 0.05) as examined. Conclusions & Inferences Colonic inflammation induced prolonged catecholaminergic innervation of sensory neurons, which may have relevance to colitis-induced chronic visceral hypersensitivity and/or referred pain.

D'Agostino DP, Colomb DG Jr, Dean JB. Effects of hyperbaric gases on membrane nanostructure and function in neurons. J Appl Physiol 106: 996 -1003, 2009. First published September 27, 2008 doi:10.1152/japplphysiol.91070.2008.-This mini-review summarizes current ideas of how hyperbaric gases (Ͼ1-10 atmospheres absolute) affect neuronal mechanisms of excitability through molecular interaction with membrane components. The dynamic nature of the lipid bilayer, its resident proteins, and the underlying cytoskeleton make each respective nanostructure a potential target for modulation by hyperbaric gases. Depending on the composition of the gas mixture, the relative concentrations of O 2 and inert gas, and total barometric pressure, the net effect of a particular gas on the cell membrane will be determined by the gas' 1) lipid solubility, 2) ability to oxidize lipids and proteins (O 2), and 3) capacity, in the compressed state, to generate localized shear and strain forces between various nanostructures. A change in the properties of any one membrane component is anticipated to change conductance of membrane-spanning ion channels and thus neuronal function.anesthesia; barosensitivity; free radicals; inert gas narcosis; nitrogen narcosis; oxidative stress; oxygen toxicity THE RANGE OF HYPERBARIC PRESSURE that humans can survive, without protection from a sealed 1-atmosphere pressure suit or submersible, extends from just beneath sea level [1 atmosphere absolute (ATA) 1 ] down to a maximum pressure of ϳ70 ATA, which is equivalent to ϳ2,300 feet of seawater (fsw) (26, 30). 2The caveat, of course, is that the aquanaut descending over this continuum of increasing ambient pressure must use specialized breathing equipment that delivers gas to their lungs at a pressure equivalent to ambient pressure. The level of inspired O 2 and the mixture of balance gases have to be selected carefully for the desired depth to avoid the powerful, wideranging, but harmful effects on neurological function of breathing hyperbaric O 2 (HBO 2 ) and hyperbaric N 2 (HBN 2 ). This means decreasing the fractional concentration of N 2 in air to Ͻ0.79 to avert the euphoric irrationality of inert gas narcosis (IGN), otherwise known as N 2 narcosis, and carefully regulating inspired O 2 to avoid the violent, uncontrollable seizures of central nervous system (CNS) O 2 toxicity (reviewed in Ref. 30). At even greater depths, in the absence of CNS O 2 toxicity and IGN, diver performance can still be impaired by a constellation of debilitating symptoms known collectively as highpressure nervous syndrome (HPNS), which includes, but is not limited to, muscular tremors, loss of coordination and memory deficits (30,84).In each case, hyperbaria is the requisite condition for induction and maintenance of neurological dysfunction. The diversity of molecular and cellular mechanisms responsible for each neurological condition is readily apparent when the suspected underlying causes are considered: CNS O 2 toxicity is attributed to the harmful effects of various sp...

Background: Preclinical evidence in rodents has suggested that inert gases, such as xenon or nitrous oxide, may be promising neuroprotective agents for treating acute ischemic stroke. This has led to many thinking that clinical trials could be initiated in the near future. However, a recent study has shown that xenon interacts with tissue-type plasminogen activator (tPA), a well-recognized approved therapy of acute

Background Chronic myelogenous leukemia (CML) is a clonal stem cell disorder accounting for 15% of adult leukemias. We aimed to determine if machine learning models could predict CML using blood cell counts prior to diagnosis. Methods We identified patients with a diagnostic test for CML (BCR-ABL1) and at least 6 consecutive prior years of differential blood cell counts between 1999 and 2020 in the largest integrated health care system in the United States. Blood cell counts from different time periods prior to CML diagnostic testing were used to train, validate, and test machine learning models. Results The sample included 1,623 patients with BCR-ABL1 positivity rate 6.2%. The predictive ability of machine learning models improved when trained with blood cell counts closer to time of diagnosis: 2 to 5 years area under the curve (AUC), 0.59 to 0.67, 0.5 to 1 years AUC, 0.75 to 0.80, at diagnosis AUC, 0.87 to 0.92. Conclusions Blood cell counts collected up to 5 years prior to diagnostic workup of CML successfully predicted the BCR-ABL1 test result. These findings suggest a machine learning model trained with blood cell counts could lead to diagnosis of CML earlier in the disease course compared to usual medical care.