Background/objective: Cortical spreading depolarization (SD) is increasingly recognized as a major contributor to secondary brain injury. Noninvasive SD monitoring would enable the institution of SD-based therapeutics. Our primary objective is to establish proof-of-concept validation that scalp DC-potentials can provide noninvasive SD detection by comparing scalp direct-current (DC)-shifts from a high-density electrode array to SDs detected by gold-standard electrocorticography (ECoG).
View Article and Find Full Text PDFElectroconvulsive therapy (ECT) is a fast-acting, highly effective, and safe treatment for medication-resistant depression. Historically, the clinical benefits of ECT have been attributed to generating a controlled seizure; however, the underlying neurobiology is understudied and remains largely unresolved. Using optical neuroimaging to probe neural activity and hemodynamics in a mouse model of ECT, we demonstrated that a second brain event follows seizure: cortical spreading depolarization (CSD).
View Article and Find Full Text PDFBackground: Impairment in cerebral autoregulation has been proposed as a potentially targetable factor in patients with aneurysmal subarachnoid hemorrhage (aSAH); however, there are different continuous measures that can be used to calculate the state of autoregulation. In addition, it has previously been proposed that there may be an association of impaired autoregulation with the occurrence of spreading depolarization (SD) events.
Methods: Study participants with invasive multimodal monitoring and aSAH were enrolled in an observational study.
Spreading depolarization (SD) is a slowly propagating wave of prolonged activation followed by a period of synaptic suppression. Some prior reports have shown potentiation of synaptic transmission after recovery from synaptic suppression and noted similarities with the phenomenon of long-term potentiation (LTP). Since SD is increasingly recognized as participating in diverse neurological disorders, it is of interest to determine whether SD indeed leads to a generalized and sustained long-term strengthening of synaptic connections.
View Article and Find Full Text PDFCerebral autoregulation is an intrinsic myogenic response of cerebral vasculature that allows for preservation of stable cerebral blood flow levels in response to changing systemic blood pressure. It is effective across a broad range of blood pressure levels through precapillary vasoconstriction and dilation. Autoregulation is difficult to directly measure and methods to indirectly ascertain cerebral autoregulation status inherently require certain assumptions.
View Article and Find Full Text PDFRed squirrel populations have declined in the UK since the introduction of the grey squirrel, due to resource competition and grey squirrels carrying a squirrelpox virus that is fatal to red squirrels. It is not known if the gut microbiota of the two species is similar and if this could impact the survival of red squirrels. The aim of this study was to profile the caecal microbiota of red and grey squirrels obtained opportunistically from a conservation programme in North Wales.
View Article and Find Full Text PDFAlthough we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation.
View Article and Find Full Text PDFSpreading depolarization (SD) is a slowly propagating wave of profound depolarization that sweeps through cortical tissue. While much emphasis has been placed on the damaging consequences of SD, there is uncertainty surrounding the potential activation of beneficial pathways such as cell survival and plasticity. The present study used unbiased assessments of gene expression to evaluate that compensatory and repair mechanisms could be recruited following SD, regardless of the induction method, which prior to this work had not been assessed.
View Article and Find Full Text PDFSpreading depolarizations (SDs) are profound waves of neuroglial depolarization that can propagate repetitively through injured brain. Recent clinical work has established SD as an important contributor to expansion of acute brain injuries and have begun to extend SD studies into other neurological disorders. A critical challenge is to determine how to selectively prevent deleterious consequences of SD.
View Article and Find Full Text PDFEffective methods for monitoring animal populations are crucial for species conservation and habitat management. Motion-activated cameras provide an affordable method for passively surveying animal presence across the landscape but have mainly been used for studying large-bodied mammals. This paper explores the relative abundance and habitat preferences of red squirrels () in coniferous forests using cameras and live trapping.
View Article and Find Full Text PDFSpreading depolarization (SD) has emerged as an important contributor to the enlargement of acute brain injuries. We previously showed that the N-methyl-D-aspartate receptor antagonist ketamine was able to prevent deleterious consequences of SD in brain slices, under conditions of metabolic compromise. The current study aimed to extend these observations into an in vivo stroke model, to test whether gradients of metabolic capacity lead to differential accumulation of calcium (Ca) following SD.
View Article and Find Full Text PDFBackground: Red Squirrels United was a UK landscape-scale grey squirrel management programme undertaken between 2016 and 2020.
Methods: A total of 11034 grey squirrels were removed by culling, with 1506 necropsied and 1405 suitable for adenovirus (AdV) or squirrelpox virus (SQPV) quantitative PCR (qPCR) analysis. Spleen, lip or hair were extracted, and DNA was isolated, with samples tested in duplicate by qPCR.
Spreading depolarization (SD) is a slowly propagating wave of profound depolarization that sweeps through cortical tissue. While much emphasis has been placed on the damaging consequences of SD, there is uncertainty surrounding the potential activation of beneficial pathways such as cell survival and plasticity. The present study used unbiased assessments of gene expression to evaluate that compensatory and repair mechanisms could be recruited following SD, regardless of the induction method, which prior to this work had not been assessed.
View Article and Find Full Text PDFPersistent posttraumatic symptoms (PPS) may manifest after a mild-moderate traumatic brain injury (mmTBI) even when standard brain imaging appears normal. Transcranial direct current stimulation (tDCS) represents a promising treatment that may ameliorate pathophysiological processes contributing to PPS. We hypothesized that in a mmTBI population, active tDCS combined with training would result in greater improvement in executive functions and post-TBI cognitive symptoms and increased resting state connectivity of the stimulated region, i.
View Article and Find Full Text PDFBackground: Spreading depolarization (SD) occurs nearly ubiquitously in malignant hemispheric stroke (MHS) and is strongly implicated in edema progression and lesion expansion. Due to this high burden of SD after infarct, it is of great interest whether SD in MHS patients can be mitigated by physiologic or pharmacologic means and whether this intervention improves clinical outcomes. Here we describe the association between physiological variables and risk of SD in MHS patients who had undergone decompressive craniectomy and present an initial case of using ketamine to target SD in MHS.
View Article and Find Full Text PDFGliomas make up nearly 40% of all central nervous system tumors, with over 50% of those being high-grade gliomas. Emerging data suggests that electrophysiologic events in the peri-tumoral region may play a role in the behavior and progression of high-grade gliomas. While seizures in the peri-tumoral zone are well described, much larger and slowly propagating waves of spreading depolarization (SD) may potentially have roles in both non-epileptic transient neurologic deficits and tumor progression.
View Article and Find Full Text PDFTouch and other types of patient stimulation are necessary in critical care and generally presumed to be beneficial. Recent pre-clinical studies as well as randomized trials assessing early mobilization have challenged the safety of such routine practices in patients with acute neurological injury such as stroke. We sought to determine whether patient stimulation could result in spreading depolarization (SD), a dramatic pathophysiological event that likely contributes to metabolic stress and ischemic expansion in such patients.
View Article and Find Full Text PDFBackground: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD).
View Article and Find Full Text PDFBackground: Delayed cerebral ischemia remains one of the principal therapeutic targets after aneurysmal subarachnoid hemorrhage. While large vessel vasospasm may contribute to ischemia, increasing evidence suggests that physiological impairment through disrupted impaired cerebral autoregulation (CA) and spreading depolarizations (SDs) also contribute to delayed cerebral ischemia and poor neurological outcome. This study seeks to explore the intermeasure correlation of different measures of CA, as well as correlation with SD and neurological outcome.
View Article and Find Full Text PDFNative red squirrels () persisted in the coastal mainland woodlands of northern Gwynedd whilst sympatric with an invasive grey squirrel () population suppressed by culling. Squirrelpox disease in the red squirrel population was recorded in 2017 and 2020/21. An autumn 2020 outbreak was associated with only 17.
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