Anesthetic Propofol Attenuates the Isoflurane-Induced Caspase-3 Activation and Aβ Oligomerization

Accumulation and deposition of β-amyloid protein (Aβ) are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase Aβ accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble Aβ oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and Aβ oligomerization in vitro and in vivo. Naïve and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for Aβ; neonatal mice; and conditioned cell culture media containing secreted human Aβ40 or Aβ42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of Aβ. Finally, isoflurane alone induces Aβ42, but not Aβ40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of Aβ42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced Aβ42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients

Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p

An Adaptive Monitoring Scheme for Automatic Control of Anaesthesia in dynamic surgical environments based on Bispectral Index and Blood Pressure.

During surgical procedures, bispectral index (BIS) is a well-known measure used to determine the patient's depth of anesthesia (DOA). However, BIS readings can be subject to interference from many factors during surgery, and other parameters such as blood pressure (BP) and heart rate (HR) can provide more stable indicators. However, anesthesiologist still consider BIS as a primary measure to determine if the patient is correctly anaesthetized while relaying on the other physiological parameters to monitor and ensure the patient's status is maintained. The automatic control of administering anesthesia using intelligent control systems has been the subject of recent research in order to alleviate the burden on the anesthetist to manually adjust drug dosage in response physiological changes for sustaining DOA. A system proposed for the automatic control of anesthesia based on type-2 Self Organizing Fuzzy Logic Controllers (T2-SOFLCs) has been shown to be effective in the control of DOA under simulated scenarios while contending with uncertainties due to signal noise and dynamic changes in pharmacodynamics (PD) and pharmacokinetic (PK) effects of the drug on the body. This study considers both BIS and BP as part of an adaptive automatic control scheme, which can adjust to the monitoring of either parameter in response to changes in the availability and reliability of BIS signals during surgery. The simulation of different control schemes using BIS data obtained during real surgical procedures to emulate noise and interference factors have been conducted. The use of either or both combined parameters for controlling the delivery Propofol to maintain safe target set points for DOA are evaluated. The results show that combing BIS and BP based on the proposed adaptive control scheme can ensure the target set points and the correct amount of drug in the body is maintained even with the intermittent loss of BIS signal that could otherwise disrupt an automated control system

Mechanical ventilation in neurocritical care patients: a systematic literature review

none5Introduction: Neurocritical care (NCC) patients often require prolonged mechanical ventilation, and they are at high risk of respiratory complications. Therefore, the potential benefit role of protective lung ventilation (PLV), which demonstrated to reduce postoperative complications in patients with acute distress respiratory syndrome, has been suggested even on NCC patients. However, PLV can increase intracranial pressure as result of permissive hypercapnia and of high airway pressures during recruitment maneuvers. The aim of this review (PROSPERO registration number: CRD42015027011) is to describe the ventilatory strategies, and in particular PLV, commonly used in NCC patients. Areas covered: We selected a total of 16 clinical studies, searching on PubMed and EMBASE databases, reporting original information on the MV on patients receiving NCC after acute brain injury, published in the last 10 years, in English language. Some of the included studies report data on a limited sample size. Expert commentary: The use of PLV techniques (PEEP, recruitment maneuvers, etc) in NCC patients is controversial. There is a wide variability among different centers in the treatment strategies and respiratory management of NCC patients, and there is the need for shared diagnostics and therapeutic studies, in order to improve the patients’ outcome.Borsellino, Beatrice; Schultz, Marcus J.; Gama de Abreu, Marcelo; Robba, Chiara; Bilotta, FedericoBorsellino, Beatrice; Schultz, Marcus J.; Gama de Abreu, Marcelo; Robba, Chiara; Bilotta, Federic