In the perioperative period, hypoxemia and hyperoxia are crucial factors that require attention, because they greatly affect patient prognoses. The pulse oximeter has been the only noninvasive monitor that can be used as a reference of oxygenation in current anesthetic management; however, in recent years, a new monitoring method that uses the oxygen reserve index (ORi™) has been developed by Masimo Corp. ORi is an index that reflects the state of moderate hyperoxia (partial pressure of arterial oxygen [PaO₂] between 100 and 200 mmHg) using a non-unit scale between 0.00 and 1.00. ORi monitoring performed together with percutaneous oxygen saturation (SpO₂) measurements may become an important technique in the field of anesthetic management, for measuring oxygenation reserve capacity. By measuring ORi, it is possible to predict hypoxemia and to detect hyperoxia at an early stage. In this review, we summarize the method of ORi, cautions for its use, and suitable cases for its use. In the near future, the monitoring of oxygen concentrations using ORi may become increasingly common for the management of respiratory function before, after, and during surgery.

Inadequate management of acute postoperative pain is associated with effects related to both physiological and psychological function. Postoperative pain increases the risk of perioperative complications, so postoperative pain should be prevented. Postoperative pain management by sufficient analgesia is important while considering the use of various kinds of analgesics. Insufficient management of postoperative pain may lead to chronic postsurgical pain (CPSP). It is suggested that CPSP is dependent not only upon biological factors but also upon psychological factors, including the type of surgery, age, physical health, mental health, and preoperative pain. As CPSP is a severe complication that may prolong hospitalization and interferes with activities of daily living (ADL) and quality of life (QoL), its prevention of development is paramount. Therefore, in order to prevent the onset of CPSP, it is necessary to craft analgesic management to prevent CPSP during the perioperative period.

Obtaining differentiated cells with high physiological functions by an efficient, but simple and rapid differentiation method is crucial for modeling neuronal diseases in vitro using human pluripotent stem cells (hPSCs). Currently, methods involving the transient expression of one or a couple of transcription factors have been established as techniques for inducing neuronal differentiation in a rapid, single step. It has also been reported that microRNAs can function as reprogramming effectors for directly reprogramming human dermal fibroblasts to neurons. In this study, we tested the effect of adding neuronal microRNAs, miRNA-9/9*, and miR-124 (miR-9/9*-124), for the neuronal induction method of hPSCs using Tet-On-driven expression of the Neurogenin2 gene (Ngn2), a proneural factor. While it has been established that Ngn2 can facilitate differentiation from pluripotent stem cells into neurons with high purity due to its neurogenic effect, a long or indefinite time is required for neuronal maturation with Ngn2 misexpression alone. With the present method, the cells maintained a high neuronal differentiation rate while exhibiting increased gene expression of neuronal maturation markers, spontaneous calcium oscillation, and high electrical activity with network bursts as assessed by a multipoint electrode system. Moreover, when applying this method to iPSCs from Alzheimer’s disease (AD) patients with presenilin-1 (PS1) or presenilin-2 (PS2) mutations, cellular phenotypes such as increased amount of extracellular secretion of amyloid β42, abnormal oxygen consumption, and increased reactive oxygen species in the cells were observed in a shorter culture period than those previously reported. Therefore, it is strongly anticipated that the induction method combining Ngn2 and miR-9/9*-124 will enable more rapid and simple screening for various types of neuronal disease phenotypes and promote drug discovery.

Cardiac arrest induces the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred to as “reperfusion injury.” Transient brain ischemia following cardiac arrest results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation, and apoptosis. The pathophysiology of post-cardiac arrest brain injury involves a complex cascade of molecular events, most of which remain unknown. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. Mitochondrial dysfunction based on the mitochondrial permeability transition after reperfusion, particularly involving the calcineurin/immunophilin signal transduction pathway, appears to play a pivotal role in the induction of neuronal cell death. The aim of this article is to discuss the underlying pathophysiology of brain damage, which is a devastating pathological condition, and highlight the central signal transduction pathway involved in brain damage, which reveals potential targets for therapeutic intervention.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction resulting from a systemic inflammatory response to infection, but the mechanism remains unclear. The mitochondrial permeability transition pore (MPTP) could play a central role in the neuronal dysfunction, induction of apoptosis, and cell death in SAE. The mitochondrial isomerase cyclophilin D (CypD) is known to control the sensitivity of MPTP induction. We, therefore, established a cecal ligation and puncture (CLP) model, which is the gold standard in sepsis research, using CypD knockout (CypD KO) mice, and analyzed the disease phenotype and the possible molecular mechanism of SAE through metabolomic analyses of brain tissue. A comparison of adult, male wild-type, and CypD KO mice demonstrated statistically significant differences in body temperature, mortality, and histological changes. In the metabolomic analysis, the main finding was the maintenance of reduced glutathione (GSH) levels and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the KO animals following CLP. In conclusion, we demonstrate that CypD is implicated in the pathogenesis of SAE, possibly related to the inhibition of MPTP induction and, as a consequence, the decreased production of ROS and other free radicals, thereby protecting mitochondrial and cellular function.