Are volatile anesthetics neuroprotective or neurotoxic?

Volatile anesthetics are one class of the most commonly used drugs. However, the mechanisms for these drugs to induce anesthesia are not fully understood and have been under intensive investigation. Two other effects of these anesthetics on the central nervous system, volatile anesthetics-induced neuroprotection and neurotoxicity, currently are hot research fields. Although data from animal studies for these two effects are extensive and convincing, clinical data for volatile anesthetics-induced neuroprotection are relatively weak. There is essentially lack of evidence to suggest volatile anesthetics-induced neurotoxicity in humans. In this regard, the contribution of general anesthesia/anesthetics to postoperative cognitive decline, a clinical entity whose existence has been supported by substantial evidence, also has not been established. This paper will be focused on reviewing the evidence, especially the clinical evidence, for volatile anesthetics-induced neuroprotection and neurotoxicity. Efforts will be devoted to facilitating the understanding of the two seemingly contradictory effects of these important drugs on the brain

Expression of the transcription factor regulatory factor X1 in the mouse brain

Limited information indicates that the regulatory factor X1 (RFX1), the prototype member of the transcription factor RFX family, may play a role in the central nervous system. Our recent study showed that knockout of the Rfx1 gene led to early embryonic death. In the present study, we showed that heterozygous Rfx1+/– mice were fertile and grew normally. An abundant amount of RFX1 proteins were expressed in the olfactory bulb, hippocampus and cerebral cortex as detected by b-galactosidase staining (the gene knockout vector contained a coding region for b-galactosidase) and immunofluorescent staining with an anti-RFX1 antibody. RFX1 positive immunostaining was mainly in the nuclei of neurons and microglial cells and was absent from the astrocytes of mouse brains. The heterozygous Rfx1+/– mice expressed RFX1 mRNA and proteins at a level similar to that in the wild-type mice in the olfactory bulb and hippocampus. The expression level of RFX1 proteins was similar in the brains of mice ranging from 15 day old embryos to four month old adults. Our results suggest a significant expression of RFX1 proteins in the mammalian brain. This expression is cell-type and brain-region specific and may take a random monoallelic expression pattern. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 344–351

Perioperative aspirin improves neurological outcome after focal brain ischemia possibly via inhibition of Notch 1 in rat

BACKGROUND: Perioperative discontinuation of aspirin is often considered due to bleeding concern. We determined whether this discontinuation affected neurological outcome after brain ischemia. METHODS: Adult male Sprague–Dawley rats were subjected to a 90-minute right middle cerebral arterial occlusion (MCAO). They received 30 mg/kg/day aspirin via gastric gavage: 1) for 2 days at 5 days before MCAO; 2) for 2 days at 5 days before MCAO and for 3 days after MCAO; 3) for 7 days before MCAO; or 4) for 7 days before MCAO and for 3 days after MCAO. Neurological outcome was evaluated 3 days after the MCAO. Ischemic penumbral cortex was harvested 1 or 3 days after MCAO for determining Notch intracellular domain (NICD), IL-6 and IL-1β levels. RESULTS: Aspirin given by regimen 2 and 3 but not by regimen 1 improved neurological outcome. Neuroprotection was achieved by N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a Notch activation inhibitor. DAPT and aspirin given only by regimen 2 and 3 reduced NICD, IL-6 and IL-1β in the ischemic penumbral cortex. NICD was found in microglial nuclei. Microglial activation in the ischemic tissues was inhibited by aspirin. CONCLUSION: Aspirin use during the perioperative period provides neuroprotection. Inhibition of Notch activation and neuroinflammation may contribute to the neuroprotection of aspirin

Perioperative Neurocognitive Disorder: State of the Preclinical Science.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research

Quantitative mapping of genetic similarity in human heritable diseases by shared mutations

Many genetic diseases exhibit considerable epidemiological comorbidity and common symptoms, which provokes debate about the extent of their etiological overlap. The rapid growth in the number of known disease-causing mutations in the Human Gene Mutation Database (HGMD) has allowed us to characterize genetic similarities between diseases by ascertaining the extent to which identical genetic mutations are shared between diseases. Using this approach, we show that 41.6% of disease pairs in all possible pairs (42, 083) exhibit a significant sharing of mutations (P value < 0.05). These mutation-related disease pairs are in agreement with heritability-based disease–disease relations in 48 neurological and psychiatric disease pairs (Spearman's correlation coefficient = 0.50; P value = 3.4 × 10−5), and share over-expressed genes significantly more often than unrelated disease pairs (1.5–1.8-fold higher; P value ≤ 1.6 × 10−4). The usefulness of mutation-related disease pairs was further demonstrated for predicting novel mutations and identifying individuals susceptible to Crohn disease. Moreover, the mutation-based disease network concurs closely with that based on phenotypes

Increased requirement for minute ventilation and negative arterial to end-tidal carbon dioxide gradient may indicate malignant hyperthermia

Abstract Characteristic signs of malignant hyperthermia (MH) include unexplained tachycardia, increased end-tidal carbon dioxide (EtCO 2 ) concentration, metabolic and respiratory acidosis, and an increase in body temperature above 38.8 C. We present the case of a patient with highly probable MH. In addition to sinus tachycardia and metabolic and respiratory acidosis, this patient also had a negative arterial to EtCO 2 gradient and an increased requirement for minute ventilation to maintain a normal EtCO 2 concentration, with signs of increased CO 2 production. Despite these signs of MH, the patient&apos;s rectal temperature monitoring equipment did not show an increase in temperature, although the temperature measured in the mouth was increased. This case illustrates the unreliability of measuring rectal temperature as a means of reflecting body temperature during MH and the usefulness of increased CO 2 production signs in helping to diagnose MH