Explore the vast range of titles available.

The mitochondria of various tissues from mice, naked mole rats (NMRs), and bats possess two mechanistically similar systems to prevent the generation of mitochondrial reactive oxygen species (mROS): hexokinases I and II and creatine kinase bound to mitochondrial membranes. Both systems operate in a manner such that one of the kinase substrates (mitochondrial ATP) is electrophoretically transported by the ATP/ADP antiporter to the catalytic site of bound hexokinase or bound creatine kinase without ATP dilution in the cytosol. One of the kinase reaction products, ADP, is transported back to the mitochondrial matrix via the antiporter, again through an electrophoretic process without cytosol dilution. The system in question continuously supports H⁺-ATP synthase with ADP until glucose or creatine is available. Under these conditions, the membrane potential, Δψ, is maintained at a lower than maximal level (i.e., mild depolarization of mitochondria). This Δψ decrease is sufficient to completely inhibit mROS generation. In 2.5-y-old mice, mild depolarization disappears in the skeletal muscles, diaphragm, heart, spleen, and brain and partially in the lung and kidney. This age-dependent decrease in the levels of bound kinases is not observed in NMRs and bats for many years. As a result, ROS-mediated protein damage, which is substantial during the aging of short-lived mice, is stabilized at low levels during the aging of long-lived NMRs and bats. It is suggested that this mitochondrial mild depolarization is a crucial component of the mitochondrial anti-aging system.

Understanding the physiological mechanisms that limit animal thermal tolerance is crucial in predicting how animals will respond to increasingly severe heat waves. Despite their importance for understanding climate change impacts, these mechanisms underlying the upper thermal tolerance limits of animals are largely unknown. It has been hypothesized that the upper thermal tolerance in fish is limited by the thermal tolerance of the brain and is ultimately caused by a global brain depolarization. In this study, we developed methods for measuring the upper thermal limit (CTmax) in larval zebrafish (Danio rerio) with simultaneous recordings of brain activity using GCaMP6s calcium imaging in both free-swimming and agar-embedded fish. We discovered that during warming, CTmax precedes, and is therefore not caused by, a global brain depolarization. Instead, the CTmax coincides with a decline in spontaneous neural activity and a loss of neural response to visual stimuli. By manipulating water oxygen levels both up and down, we found that oxygen availability during heating affects locomotor-related neural activity, the neural response to visual stimuli, and CTmax. Our results suggest that the mechanism limiting the upper thermal tolerance in zebrafish larvae is insufficient oxygen availability causing impaired brain function.

BackgroundNeuroinflammation has an important role in the pathophysiology of migraine, which is a complex neuro-glio-vascular disorder. The main aim of this review is to highlight findings of cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma from the inflammasome perspective. In addition, we discuss the limited data of the contribution of inflammasomes to other aspects of migraine pathophysiology, foremost the activation of the trigeminovascular system and thereby the generation of migraine pain.Main bodyInflammasomes are signaling multiprotein complexes and key components of the innate immune system. Their activation causes the production of inflammatory cytokines that can stimulate trigeminal neurons and are thus relevant to the generation of migraine pain. The contribution of inflammasome activation to pain signaling has attracted considerable attention in recent years. Nucleotide-binding domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is the best characterized inflammasome and there is emerging evidence of its role in a variety of inflammatory pain conditions, including migraine. In this review, we discuss, from an inflammasome point of view, cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma, the connection with genetic factors that make the brain vulnerable to CSD, and the relation of the inflammasome with diseases that are co-morbid with migraine, including stroke, epilepsy, and the possible links with COVID-19 infection.ConclusionNeuroinflammatory pathways, specifically those involving inflammasome proteins, seem promising candidates as treatment targets, and perhaps even biomarkers, in migraine.

Purpose of ReviewAneurysmal subarachnoid hemorrhage remains a devastating disease process despite medical advances made over the past 3 decades. Much of the focus was on prevention and treatment of vasospasm to reduce delayed cerebral ischemia and improve outcome. In recent years, there has been a shift of focus onto early brain injury as the precursor to delayed cerebral ischemia. This review will focus on the most recent data surrounding the pathophysiology of aneurysmal subarachnoid hemorrhage and current management strategies.Recent FindingsThere is a paucity of successful trials in the management of subarachnoid hemorrhage likely related to the targeting of vasospasm. Pathophysiological changes occurring at the time of aneurysmal rupture lead to early brain injury including cerebral edema, inflammation, and spreading depolarization. These events result in microvascular collapse, vasospasm, and ultimately delayed cerebral ischemia.SummaryManagement of aneurysmal subarachnoid hemorrhage has remained the same over the past few decades. No recent trials have resulted in new treatments. However, our understanding of the pathophysiology is rapidly expanding and will advise future therapeutic targets.

Dielectric and magnetic spherical hollow shells are employed in many applications as standard building units. These structures are commonly subjected to size reduction to obtain a high surface area/volume ratio, a property that is in favor of specific applications. However, the size reduction enhances the importance of physical mechanisms that originate from surfaces, such as the depolarization effect. Here we tackle the problem of dielectric and magnetic spherical hollow shells, consisting of a linear, homogeneous and isotropic parent material, subjected to an external potential, Uextr, of any spatial form (either dc (static) or ac of low-frequency (quasistatic limit)). By applying the method-of-linear-recursive-solution (MLRS) to the Laplace equation, we calculate analytically the internal, Uintr, and total, Utotr, potentials in respect to the external one, Uextr. From Uintr and Utotr we calculate all relevant scalar and vector physical entities of interest. The MLRS unveils straightforwardly the existence of two distinct depolarization factors, Nl=l/(2l+1) and Nl+1=(l+1)/(2l+1), both depending on the degree, l, however not on the order, m, of the mode of the external potential, Uext(l,m)r. These depolarization factors, Nl and Nl+1, originate from the outer, r=b, and inner, r=a, surfaces and are accompanied by two extrinsic susceptibilities, χe,lext=χe /(1+Nlχe ) and χe,l+1ext=χe /(1+Nl+1χe ), respectively. Importantly, Nl+Nl+1=1, irrespective of the degree, l, as it should. The properties of spherical hollow shells are investigated through analytical modeling and detailed simulations, with emphasis on application-relevant scenarios including resonance phenomena in scattering, quantitative materials characterization, and shielding/distortion. The generic MLRS strategy provides a flexible and reliable route for analyzing depolarization processes in other dielectric and magnetic building-unit geometries encountered in practice.

Background Spreading depolarization (SD) is a wave of neuronal and glial depolarization observed in various neurological conditions, including stroke, traumatic brain injury, subarachnoid haemorrhage, and migraine aura. This depolarization disrupts ion homeostasis, creating high energy demand for recovery. While healthy tissue can compensate, pathological tissue may develop ischemia, worsening brain injury and outcomes. Identifying inflammatory mediators that exacerbate neuroinflammation after SD could guide targeted therapies. This review aimed to explore both the neuroinflammatory effects of SD and the impact of experimentally induced inflammatory states on SD characteristics. Methods PubMed and Scopus were systematically searched for preclinical studies that examined the effects of SD on inflammation, and the effects of an inflammatory state on SD responses. Data extracted included authors, publication details, study type, animal characteristics, group sizes, exclusions, relevant findings, and limitations. Additional details were collected for studies on SD and neuroinflammation, including induction methods, inflammatory markers and SD characteristics in altered inflammatory states. Results Several studies indicated that SD triggered a robust neuroinflammatory response, marked by upregulation of cytokines—interleukin-1β, tumour necrosis factor-α, and interleukin-6—alongside transcription factors such as nuclear factor kappa B, and activation of astrocytes and microglia. Key mediators including toll-like receptors, cyclooxygenase-2 and high mobility group box 1 were also implicated, with evidence of neurogenic involvement via the release of calcitonin gene-related peptide. Differences in inflammatory responses were identified between single and multiple SD induction. Studies measuring the effect of altered inflammatory states on SD propagation were limited. Models of peripheral inflammation and non-demyelinating autoimmune encephalomyelitis did not lead to significant alterations in SD characteristics. However, administration of tumour necrosis factor was able to reduce SD amplitude, suggesting a possible neuroprotective effect. Conclusion This review suggests potential mechanisms underlying the role of SD in neurological disorders. While SD is associated with inflammatory markers, evidence for the impact of heightened inflammatory states on cortical susceptibility to SD remains limited. Significant methodological variability and inflammatory disease models underscores the need for standardization to validate these findings. Further research into these mechanisms could identify novel therapeutic targets to mitigate SD-related neuroinflammation in neurological disorders.

Permanently polarized biphasic calcium phosphate composed of hydroxyapatite and brushite (pp‐HAp/Bru), which is prepared by applying the thermally stimulated polarization treatment to calcined HAp, is used as a sustainable catalyst to transform CO2 into value‐added products. In this work, the stability of pp‐HAp/Bru is studied from structural, electrical, and catalytic perspectives, applying a thermal depolarization process with temperatures (Td) ranging from 200 to 1000 °C. Results show that the Bru phase is not stable when Td ≤ 400 °C, while the structure of the HAp refines and transforms into Bru when Td ≥ 600 °C. Besides, the electrical resistance and capacitance of the pp‐HAp/Bru increase with Td, evidencing the progressive electrical depolarization of the material. Thermal depolarization also influences the specific orientation of the OH– ions, which is partially lost (≈50%). All such changes affect the catalytic efficiency of pp‐HAp/Bru, which is proven using a reaction that transforms CO2 gas into acetic acid and formic acid. Results show that the total reaction yield linearly decreases with increasing Td. Based on such observations, a simple process is designed that allows the reconstitution of the structure and restores the activity of such green catalysts. The thermal depolarization of permanently polarized biphasic calcium phosphate, a green catalyst composed of hydroxyapatite and brushite, is examined, investigating the effect of the depolarization temperature on the properties at the interface and the catalytic efficiency for CO2 fixation. Furthermore, a treatment to re‐constitute the catalyst, which maintains, or even enhances, the catalytic efficiency is proposed.

Background Both seizures and spreading depolarizations (SDs) are commonly detected using electrocorticography (ECoG) after severe traumatic brain injury (TBI). A close relationship between seizures and SDs has been described, but the implications of detecting either or both remain unclear. We sought to characterize the relationship between these two phenomena and their clinical significance. Methods We performed a post hoc analysis of a prospective observational clinical study of patients with severe TBI requiring neurosurgery at five academic neurotrauma centers. A subdural electrode array was placed intraoperatively and ECoG was recorded during intensive care. SDs, seizures, and high-frequency background characteristics were quantified offline using published standards and terminology. The primary outcome was the Glasgow Outcome Scale-Extended score at 6 months post injury. Results There were 138 patients with valid ECoG recordings; the mean age was 47 ± 19 years, and 104 (75%) were men. Overall, 2,219 ECoG-detected seizures occurred in 38 of 138 (28%) patients in a bimodal pattern, with peak incidences at 1.7–1.8 days and 3.8–4.0 days post injury. Seizures detected on scalp electroencephalography (EEG) were diagnosed by standard clinical care in only 18 of 138 (13%). Of 15 patients with ECoG-detected seizures and contemporaneous scalp EEG, seven (47%) had no definite scalp EEG correlate. ECoG-detected seizures were significantly associated with the severity and number of SDs, which occurred in 83 of 138 (60%) of patients. Temporal interactions were observed in 17 of 24 (70.8%) patients with both ECoG-detected seizures and SDs. After controlling for known prognostic covariates and the presence of SDs, seizures detected on either ECoG or scalp EEG did not have an independent association with 6-month functional outcome but portended worse outcome among those with clustered or isoelectric SDs. Conclusions In patients with severe TBI requiring neurosurgery, seizures were half as common as SDs. Seizures would have gone undetected without ECoG monitoring in 20% of patients. Although seizures alone did not influence 6-month functional outcomes in this cohort, they were independently associated with electrographic worsening and a lack of motor improvement following surgery. Temporal interactions between ECoG-detected seizures and SDs were common and held prognostic implications. Together, seizures and SDs may occur along a dynamic continuum of factors critical to the development of secondary brain injury. ECoG provides information integral to the clinical management of patients with TBI.

Background Spreading depolarizations (SDs) are self-propagating waves of neuronal and glial depolarizations often seen in neurological conditions in both humans and animal models. Because SD is thought to worsen neurological injury, the role of SD in a variety of cerebral insults has garnered significant investigation. Anoxic SD is a type of SD that occurs because of anoxia or asphyxia. Although asphyxia leading to a severe drop in blood pressure may affect cerebral hemodynamics and is widely known to cause anoxic SD, the effect of anoxic SD on peripheral blood pressure in the extremities has not been investigated. This relationship is especially important to understand for conditions such as circulatory shock and cardiac arrest that directly affect both peripheral and cerebral perfusion in addition to producing anoxic SD in the brain. Methods In this study, we used a rat model of asphyxial cardiac arrest to investigate the role of anoxic SD on cerebral hemodynamics and metabolism, peripheral blood pressure, and the relationship between these variables in 8- to 12-week-old male rats. We incorporated a multimodal monitoring platform measuring cortical direct current simultaneously with optical imaging. Results We found that during anoxic SD, there is decoupling of peripheral blood pressure from cerebral blood flow and metabolism. We also observed that anoxic SD may modify cerebrovascular resistance. Furthermore, shorter time difference between anoxic SDs measured at different locations in the same rat was associated with better neurological outcome on the basis of the recovery of electrocorticography activity (bursting) immediately post resuscitation and the neurological deficit scale score 24 h post resuscitation. Conclusions To our knowledge, this is the first study to quantify the relationship between peripheral blood pressure, cerebral hemodynamics and metabolism, and neurological outcome in anoxic SD. These results indicate that the characteristics of SD may not be limited to cerebral hemodynamics and metabolism but rather may also encompass changes in peripheral blood flow, possibly through a brain–heart connection, providing new insights into the role of anoxic SD in global ischemia and recovery.