Nerve agents (NAs) are potent organophosphorus (OP) compounds with applications in chemical warfare. OP compounds act by inhibiting acetylcholinesterase (AChE). Soman (O-pinacolyl methylphosphonofluoridate) is one of the most potent NAs. It is well known that small doses of NAs can be lethal, and that even non-lethal exposure leads to long-term mental debilitation/neurological damage. However, the neuropathology following exposure to sub-lethal nerve agents is not well understood. In this study, we examined changes in tissue oxygenation (pO) in the cortex and hippocampus after a sub-lethal dose of soman [80-90 μg/kg; subcutaneous]. pO changes can provide information regarding oxygen delivery and utilization and may be indicative of a disruption in cerebral blood flow and/or metabolism. Changes in oxygenation were measured with chronically implanted oxygen sensors in awake and freely moving rats. Measurements were taken before, during, and after soman-induced convulsive seizures. Soman exposure resulted in an immediate increase in pO in the cortex, followed by an even greater increase that precedes the onset of soman-induced convulsive seizures. The rise in hippocampus pO was delayed relative to the cortex, although the general pattern of brain oxygenation between these two regions was similar. After convulsive seizures began, pO levels declined but usually remained hyperoxygenated. Following the decline in pO, low frequency cycles of large amplitude changes were observed in both the cortex and hippocampus. This pattern is consistent with recurring seizures. Measuring real-time changes in brain pO provides new information on the physiological status of the brain following soman exposure. These results highlight that the measurement of brain oxygenation could provide a sensitive marker of nerve agent exposure and serve as a biomarker for treatment studies.
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http://dx.doi.org/10.1016/j.neuro.2018.01.007 | DOI Listing |
J Physiol
January 2025
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
The mechanisms that drive placental dysfunction in pregnancies complicated by hypoxia and fetal growth restriction remain poorly understood. Changes to mitochondrial respiration contribute to cellular dysfunction in conditions of hypoxia and have been implicated in the pathoaetiology of pregnancy complications, such as pre-eclampsia. We used bespoke isobaric hypoxic chambers and a combination of functional, molecular and imaging techniques to study cellular metabolism and mitochondrial dynamics in sheep undergoing hypoxic pregnancy.
View Article and Find Full Text PDFOxidative stress is a prominent feature of Alzheimer's disease. Within this context, cholesterol undergoes oxidation, producing the pro-inflammatory product 7-ketocholesterol (7-KC). In this study, we observe elevated levels of 7-KC in the brains of the 3xTg mouse model of AD.
View Article and Find Full Text PDFCerebrospinal fluid (CSF) dynamics, driven by sensory stimulation-induced neuronal activity, is crucial for maintaining homeostasis and clearing metabolic waste. However, it remains unclear whether such CSF flow is impaired in age-related neurodegenerative diseases of the visual system. This study addresses this gap by examining CSF flow during visual stimulation in glaucoma patients and healthy older adults using functional magnetic resonance imaging.
View Article and Find Full Text PDFThe complementary strengths of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have driven extensive research into integrating these two noninvasive modalities to better understand the neural mechanisms underlying cognitive, sensory, and motor functions. However, the precise neural patterns associated with motor functions, especially imagined movements, remain unclear. Specifically, the correlations between electrophysiological responses and hemodynamic activations during executed and imagined movements have not been fully elucidated at a whole-brain level.
View Article and Find Full Text PDFDrug Des Devel Ther
January 2025
Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Purpose: This study aimed to assess the protective effect of a clinical dose esketamine on cerebral ischemia/reperfusion (I/R) injury and to reveal the potential mechanisms associated with microglial polarization and autophagy.
Methods: Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult rats and simulated by oxygen-glucose deprivation (OGD) in BV-2 microglial cells. Neurological and sensorimotor function, cerebral infarct volume, histopathological changes, mitochondrial morphological changes, and apoptosis of ischemic brain tissues were assessed in the presence or absence of esketamine and the autophagy inducer rapamycin.
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