4'-O-methylbavachalcone alleviates ischemic stroke injury by inhibiting parthanatos and promoting SIRT3.

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.

Arousal state transitions occlude sensory-evoked neurovascular coupling in neonatal mice.

In the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drive vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes.

Early prediction of remaining useful life for lithium-ion batteries based on CEEMDAN-transformer-DNN hybrid model.

A reliable and safe energy storage system utilizing lithium-ion batteries relies on the early prediction of remaining useful life (RUL). Despite this, accurate capacity prediction can be challenging if little historical capacity data is available due to the capacity regeneration and the complexity of capacity degradation over multiple time scales. In this study, data decomposition, transformers, and deep neural networks (DNNs) are combined to develop a model of RUL prediction for lithium-ion batteries. Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is used for battery capacity sequential data to account for the capacity regeneration effect. The transformer networks are leveraged to predict each component of capacity regeneration thus improving the model's ability to handle long sequences while reducing the amount of data. The global degradation trend is predicted using a deep neural network. We validated the early prediction performance of the model using two publicly available battery datasets. Results show that the prediction model only uses 25%-30% data to achieve high accuracy. In the two public data sets, the RMSE errors were 0.0208 and 0.0337, respectively. A high level of accuracy is achieved with the model proposed in this study, which is based on fewer capacity data.

Aging drives cerebrovascular network remodeling and functional changes in the mouse brain.

Aging is the largest risk factor for neurodegenerative disorders, and commonly associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts the vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods (serial two-photon tomography and light sheet microscopy) and in vivo imaging (wide field optical spectroscopy and two-photon imaging) to determine detailed changes in aged cerebrovascular networks. Whole-brain vascular tracing showed an overall ~10% decrease in vascular length and branching density, and light sheet imaging with 3D immunolabeling revealed increased arteriole tortuosity in aged brains. Vasculature and pericyte densities showed significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. Moreover, in vivo imaging in awake mice identified delays in neurovascular coupling and disrupted blood oxygenation. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.

Arousal state transitions occlude sensory-evoked neurovascular coupling in neonatal mice.

In the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drives vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes. Significance Statement: In the adult brain, increases in neural activity are often followed by vasodilation, allowing activity to be monitored using optical or magnetic resonance imaging. However, in neonates, sensory stimulation can drive vasoconstriction, whose origin was not understood. We used optical and magnetic resonance imaging approaches to investigate hemodynamics in neonatal mice. We found that sensory-induced vasoconstriction occurred when the mice were asleep, as sleep is associated with dilation of the vasculature of the brain relative to the awake state. The stimulus awakens the mice, causing a constriction due to the arousal state change. Our study shows the importance of monitoring arousal state, particularly when investigating subjects that may sleep, and the dominance arousal effects on brain hemodynamics.

Could respiration-driven blood oxygen changes modulate neural activity?

Oxygen is critical for neural metabolism, but under most physiological conditions, oxygen levels in the brain are far more than are required. Oxygen levels can be dynamically increased by increases in respiration rate that are tied to the arousal state of the brain and cognition, and not necessarily linked to exertion by the body. Why these changes in respiration occur when oxygen is already adequate has been a long-standing puzzle. In humans, performance on cognitive tasks can be affected by very high or very low oxygen levels, but whether the physiological changes in blood oxygenation produced by respiration have an appreciable effect is an open question. Oxygen has direct effects on potassium channels, increases the degradation rate of nitric oxide, and is rate limiting for the synthesis of some neuromodulators. We discuss whether oxygenation changes due to respiration contribute to neural dynamics associated with attention and arousal.

The function of miR-637 in non-small cell lung cancer progression and prognosis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and poor prognosis. miR-637 has been reported to regulate tumor progression and act as a prognosis biomarker of various cancers. Its functional role in NSCLC was investigated in this study. METHODS: The expression level of miR-637 in NSCLC tissues and adjacent normal tissues of 123 NSCLC patients was analyzed by qRT-PCR. The association between miR-637 and clinical pathological features in the prognosis of patients was analyzed. Cell transfection was performed to overexpress or knockdown miR-637 in H1299 and HCC827. The proliferation, migration, and invasion of H1299 and HCC827 were evaluated by CCK8 and Transwell assay. RESULTS: miR-637 expression was significantly decreased in NSCLC tissues and cell lines relative to normal tissues and cells. The survival rate of NSCLC patients with low miR-637 expression was lower than that of patients with high miR-637 expression. Additionally, miR-637 served as a tumor suppressor that inhibited cell proliferation, migration, and invasion of NSCLC. CONCLUSION: Downregulation of miR-637 in NSCLC was associated with TNM stage and poor prognosis of patients and served as a tumor suppressor in NSCLC. These results provide a potential strategy to control NSCLC.

Quantitative relationship between cerebrovascular network and neuronal cell types in mice.

The cerebrovasculature and its mural cells must meet brain regional energy demands, but how their spatial relationship with different neuronal cell types varies across the brain remains largely unknown. Here we apply brain-wide mapping methods to comprehensively define the quantitative relationships between the cerebrovasculature, capillary pericytes, and glutamatergic and GABAergic neurons, including neuronal nitric oxide synthase-positive (nNOS+) neurons and their subtypes in adult mice. Our results show high densities of vasculature with high fluid conductance and capillary pericytes in primary motor sensory cortices compared with association cortices that show significant positive and negative correlations with energy-demanding parvalbumin+ and vasomotor nNOS+ neurons, respectively. Thalamo-striatal areas that are connected to primary motor sensory cortices also show high densities of vasculature and pericytes, suggesting dense energy support for motor sensory processing areas. Our cellular-resolution resource offers opportunities to examine spatial relationships between the cerebrovascular network and neuronal cell composition in largely understudied subcortical areas.

Behavioral and physiological monitoring for awake neurovascular coupling experiments: a how-to guide.

Significance: Functional brain imaging in awake animal models is a popular and powerful technique that allows the investigation of neurovascular coupling (NVC) under physiological conditions. However, ubiquitous facial and body motions (fidgeting) are prime drivers of spontaneous fluctuations in neural and hemodynamic signals. During periods without movement, animals can rapidly transition into sleep, and the hemodynamic signals tied to arousal state changes can be several times larger than sensory-evoked responses. Given the outsized influence of facial and body motions and arousal signals in neural and hemodynamic signals, it is imperative to detect and monitor these events in experiments with un-anesthetized animals. Aim: To cover the importance of monitoring behavioral state in imaging experiments using un-anesthetized rodents, and describe how to incorporate detailed behavioral and physiological measurements in imaging experiments. Approach: We review the effects of movements and sleep-related signals (heart rate, respiration rate, electromyography, intracranial pressure, whisking, and other body movements) on brain hemodynamics and electrophysiological signals, with a focus on head-fixed experimental setup. We summarize the measurement methods currently used in animal models for detection of those behaviors and arousal changes. We then provide a guide on how to incorporate this measurements with functional brain imaging and electrophysiology measurements. Results: We provide a how-to guide on monitoring and interpreting a variety of physiological signals and their applications to NVC experiments in awake behaving mice. Conclusion: This guide facilitates the application of neuroimaging in awake animal models and provides neuroscientists with a standard approach for monitoring behavior and other associated physiological parameters in head-fixed animals.

Role of the renin-angiotensin system in NETosis in the coronavirus disease 2019 (COVID-19).

Myocardial infarction and stroke are the leading causes of death in the world. Numerous evidence has confirmed that hypertension promotes thrombosis and induces myocardial infarction and stroke. Recent findings reveal that neutrophil extracellular traps (NETs) are involved in the induction of myocardial infarction and stroke. Meanwhile, patients with severe COVID-19 suffer from complications such as myocardial infarction and stroke with pathological signs of NETs. Due to the extremely low amount of virus detected in the blood and remote organs (e.g., heart, brain and kidney) in a few cases, it is difficult to explain the mechanism by which the virus triggers NETosis, and there may be a different mechanism than in the lung. A large number of studies have found that the renin-angiotensin system regulates the NETosis at multiple levels in patients with COVID-19, such as endocytosis of SARS-COV-2, abnormal angiotensin II levels, neutrophil activation and procoagulant function at multiple levels, which may contribute to the formation of reticular structure and thrombosis. The treatment of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARBs) and neutrophil recruitment and active antagonists helps to regulate blood pressure and reduce the risk of net and thrombosis. The review will explore the possible role of the angiotensin system in the formation of NETs in severe COVID-19.

lncRNA RMRP predicts poor prognosis and mediates tumor progression of esophageal squamous cell carcinoma by regulating miR-613/ neuropilin 2 (NRP2) axis.

The RNA component of mitochondrial RNA processing endoribonuclease (RMRP) has been reported to play a role in the development of various human diseases. The clinical significance and biological function of RMRP in the progression of esophageal squamous cell carcinoma (ESCC) and the potential mechanism were investigated in this study.A total of 118 ESCC patients were included in this study. The expression of RMRP in ESCC was analyzed with the help of the polymerase chain reaction. The cell counting kit 8 assay was employed to evaluate the role of RMRP in cell proliferation, and its functions in cell migration and invasion were assessed by the Transwell assays. Meanwhile, the clinical significance of RMRP in ESCC was estimated with Kaplan-Meier and Cox regression analysis.RMRP was significantly upregulated in ESCC, which was associated with the lymph node metastasis status, the TNM stage of patients, and a poor outcome of ESCC patients. Moreover, RMRP promoted the proliferation, migration, and invasion of ESCC cells via regulating miR-613/NRP2.RMRP was involved in the progression of ESCC through regulating the miR-613/NRP2 axis, which provides a potential target for the treatment of ESCC.

Origins of 1/f-like tissue oxygenation fluctuations in the murine cortex.

The concentration of oxygen in the brain spontaneously fluctuates, and the distribution of power in these fluctuations has a 1/f-like spectra, where the power present at low frequencies of the power spectrum is orders of magnitude higher than at higher frequencies. Though these oscillations have been interpreted as being driven by neural activity, the origin of these 1/f-like oscillations is not well understood. Here, to gain insight of the origin of the 1/f-like oxygen fluctuations, we investigated the dynamics of tissue oxygenation and neural activity in awake behaving mice. We found that oxygen signal recorded from the cortex of mice had 1/f-like spectra. However, band-limited power in the local field potential did not show corresponding 1/f-like fluctuations. When local neural activity was suppressed, the 1/f-like fluctuations in oxygen concentration persisted. Two-photon measurements of erythrocyte spacing fluctuations and mathematical modeling show that stochastic fluctuations in erythrocyte flow could underlie 1/f-like dynamics in oxygenation. These results suggest that the discrete nature of erythrocytes and their irregular flow, rather than fluctuations in neural activity, could drive 1/f-like fluctuations in tissue oxygenation.

Modified technique of closing the port site after multiport thoracoscopic surgery using the shingled suture technique: a single centre experience.

BACKGROUND: Due to improvements in operative techniques and medical equipment, video-assisted thoracoscopic surgery has become a mainstay of thoracic surgery. Nevertheless, in multiport thoracoscopic surgery, there have been no substantial advances related to the improvement of the esthetics of the site of the chest tube kept for postoperative drainage of intrathoracic fluid and decompression of air leak after thoracoscopic surgery. Leakage of fluid and air around the site of the chest tube can be extremely bothersome to patients. METHODS: From March 2019 to April 2020, we used a modified technique of closing the port site in 67 patients and the traditional method in 51 patients undergoing multiport thoracoscopic surgery due to lung disease or mediastinal disease. We recorded patients' age, gender, body mass index, surgical method, postoperative drainage time, and postoperative complications.The NRS pain scale was used to score the pain in each patient on the day of extubation.The PSAS and the OSAS were used for the assessment of scars one month after surgery. RESULTS: In the modified technique group, only one patient (1.49%) had pleural effusion leakage, compared with five patients (9.80%) in the traditional method group (P < 0.05). There were no significant differences in the pain of extubating and wound dehiscence between the two groups. However,the incidence rates of wound dehiscence in the modified technique group were lower than in the traditional method group. There were no post-removal pneumothorax and wound infection in either of the groups. Significant differences in the PSAS and OSAS were observed between the groups,where the modified technique group was superior to the traditional method group. CONCLUSIONS: The modified technique of port site closure is a leak-proof method of fixation of the chest tube after multiport thoracoscopic surgery. Moreover, it is effective and preserves the esthetic appearance of the skin.

Long non-coding RNA KCNQ1 overlapping transcript 1 promotes the progression of esophageal squamous cell carcinoma by adsorbing microRNA-133b.

OBJECTIVE: The long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) exerts vital regulatory functions in diverse tumors. However, the biological function of KCNQ1OT1 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: KCNQ1OT1 expression was detected in ESCC tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were detected by the CCK-8 assay, EdU assay, flow cytometry analysis, and Transwell experiments, respectively. Bioinformatics analysis, luciferase reporter experiments, and RNA immunoprecipitation assays were used to predict and validate the regulatory relationships between KCNQ1OT1, microRNA-133b (miR-133b) and epidermal growth factor receptor (EGFR). RESULTS: KCNQ1OT1 expression was remarkably upregulated in ESCC tissues and cell lines. Overexpression of KCNQ1OT1 markedly promoted ESCC cell proliferation, migration, and invasion and enhanced the expression of N-cadherin, MMP-2, and MMP-9, but inhibited apoptosis and E-cadherin expression in ESCC cell lines; KCNQ1OT1 knockdown exerted the opposite effects. KCNQ1OT1 could directly bind to miR-133b and suppress its expression, and miR-133b reversed the effects of KCNQ1OT1 overexpression in ESCC cells. MiR-133b reduced the expression of epidermal growth factor receptor (EGFR); further, KCNQ1OT1 activated the phosphatidylinositol 3-kinase/AKT serine/threonine kinase 1 (PI3K/AKT) signaling pathway by repressing miR-133b repression and indirectly upregulating EGFR. KCNQ1OT1 expression was positively correlated with EGFR mRNA expression and negatively correlated with miR-133b expression. CONCLUSION: KCNQ1OT1 facilitates ESCC progression by sponging miR-133b and activating the EGFR/PI3K/AKT pathway.

Long non-coding RNA KCNQ1 overlapping transcript 1 promotes the progression of esophageal squamous cell carcinoma by adsorbing microRNA-133b

OBJECTIVE: The long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) exerts vital regulatory functions in diverse tumors. However, the biological function of KCNQ1OT1 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: KCNQ1OT1 expression was detected in ESCC tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were detected by the CCK-8 assay, EdU assay, flow cytometry analysis, and Transwell experiments, respectively. Bioinformatics analysis, luciferase reporter experiments, and RNA immunoprecipitation assays were used to predict and validate the regulatory relationships between KCNQ1OT1, microRNA-133b (miR-133b) and epidermal growth factor receptor (EGFR). RESULTS: KCNQ1OT1 expression was remarkably upregulated in ESCC tissues and cell lines. Overexpression of KCNQ1OT1 markedly promoted ESCC cell proliferation, migration, and invasion and enhanced the expression of N-cadherin, MMP-2, and MMP-9, but inhibited apoptosis and E-cadherin expression in ESCC cell lines; KCNQ1OT1 knockdown exerted the opposite effects. KCNQ1OT1 could directly bind to miR-133b and suppress its expression, and miR-133b reversed the effects of KCNQ1OT1 overexpression in ESCC cells. MiR-133b reduced the expression of epidermal growth factor receptor (EGFR); further, KCNQ1OT1 activated the phosphatidylinositol 3-kinase/AKT serine/threonine kinase 1 (PI3K/AKT) signaling pathway by repressing miR-133b repression and indirectly upregulating EGFR. KCNQ1OT1 expression was positively correlated with EGFR mRNA expression and negatively correlated with miR-133b expression. CONCLUSION: KCNQ1OT1 facilitates ESCC progression by sponging miR-133b and activating the EGFR/PI3K/AKT pathway.

Patterns of recurrence in adenocarcinoma of the esophagogastric junction: a retrospective study.

BACKGROUND: The prognosis of adenocarcinoma of the esophagogastric junction (AEG) is poor. Understanding the postoperative recurrence pattern of AEG is helpful to verify the effectiveness of treatment and optimize subsequent treatment, so as to improve prognosis. METHODS: This single-center retrospective study included patients with stage III AEG who underwent surgical treatment between January 2009 and December 2016. According to the different postoperative treatment arm, patients were divided into surgery and surgery plus chemotherapy groups. Recurrence-free survival was used as the outcome to compare the recurrence site and pattern between the groups. RESULTS: In total, were 306 patients enrolled, 123 in the surgery group and 183 in the surgery plus chemotherapy group. During follow-up (median 17.1 months) of 24 months after surgery, 62.0% of patients had tumor recurrence. The overall recurrence rates in the surgery and surgery plus chemotherapy groups were 86.9% and 77.0%, respectively. The recurrence patterns of both groups were mainly distant metastasis. Postoperative chemotherapy reduced the incidence of hematogenous dissemination from 51.2 to 42.0%. Multivariate Cox analysis showed that the pN stage increased the risk of recurrence, while surgery plus chemotherapy reduced the risk. CONCLUSIONS: Patients with AEG have a risk of hematogenous dissemination after surgery. Postoperative treatment arm and pN stage were independent risk factors in patients with AEG. Surgery plus chemotherapy can improve recurrence-free survival and reduce distant metastasis, but they do not have a beneficial role in controlling local recurrence.

Semaphorin 3F Serves as a Tumor Suppressor in Esophageal Squamous Cell Carcinoma and is Associated With Lymph Node Metastasis in Disease Progression.

BACKGROUND: Esophageal squamous cell carcinoma is one of the leading aggressive malignancies with high mortality. Semaphorin 3F has been reported to be involved in lymphangiogenesis by interacting the vascular endothelial growth factor C/neuropilin 2 axis. This study aimed to assess the clinical and functional role of semaphorin 3F and preliminarily evaluate the relationship between semaphorin 3F and lymph node metastasis in esophageal squamous cell carcinoma. METHODS: The messenger RNA expression of semaphorin 3F was analyzed using quantitative real-time polymerase chain reaction. The expression differences of semaphorin 3F between patients having esophageal squamous cell carcinoma with and without lymph node metastasis were assessed, and the correlation of semaphorin 3F with vascular endothelial growth factor C and neuropilin 2 was estimated. The prognostic value of semaphorin 3F was evaluated using Kaplan-Meier survival curves and Cox regression analysis. Gain- and loss-functional cell experiments were performed to explore the biological function of semaphorin 3F, vascular endothelial growth factor C, and neuropilin 2. RESULTS: The messenger RNA expression of semaphorin 3F was reduced in esophageal squamous cell carcinoma tissues compared with normal tissues, and lower semaphorin 3F expression was observed in patients having esophageal squamous cell carcinoma with positive lymph node metastasis. Semaphorin 3F expression was associated with lymph node metastasis and negatively correlated with vascular endothelial growth factor C and neuropilin 2. Lower semaphorin 3F expression was related to a poor overall survival of esophageal squamous cell carcinoma and served as an independent prognostic indicator. In esophageal squamous cell carcinoma cells, semaphorin 3F messenger RNA expression was also decreased compared with normal cells, and the overexpression of semaphorin 3F could significantly inhibit cell proliferation, migration, and invasion. The downregulation of vascular endothelial growth factor C and neuropilin 2 could inhibit cell proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. CONCLUSION: All data indicate that semaphorin 3F serves as a potential prognostic biomarker and tumor suppressor of esophageal squamous cell carcinoma and may be involved in the lymph node metastasis development through regulating neuropilin 2.

Cerebral oxygenation during locomotion is modulated by respiration.

In the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animal remains unclear. We investigated to what extent cerebral oxygenation varies during locomotion. We measured oxygen levels in the cortex of awake, head-fixed mice during locomotion using polarography, spectroscopy, and two-photon phosphorescence lifetime measurements of oxygen sensors. We find that locomotion significantly and globally increases cerebral oxygenation, specifically in areas involved in locomotion, as well as in the frontal cortex and the olfactory bulb. The oxygenation increase persists when neural activity and functional hyperemia are blocked, occurred both in the tissue and in arteries feeding the brain, and is tightly correlated with respiration rate and the phase of respiration cycle. Thus, breathing rate is a key modulator of cerebral oxygenation and should be monitored during hemodynamic imaging, such as in BOLD fMRI.

Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate.

Cerebrospinal fluid (CSF) flows through the brain, transporting chemical signals and removing waste. CSF production in the brain is balanced by a constant outflow of CSF, the anatomical basis of which is poorly understood. Here, we characterized the anatomy and physiological function of the CSF outflow pathway along the olfactory sensory nerves through the cribriform plate, and into the nasal epithelia. Chemical ablation of olfactory sensory nerves greatly reduced outflow of CSF through the cribriform plate. The reduction in CSF outflow did not cause an increase in intracranial pressure (ICP), consistent with an alteration in the pattern of CSF drainage or production. Our results suggest that damage to olfactory sensory neurons (such as from air pollution) could contribute to altered CSF turnover and flow, providing a potential mechanism for neurological diseases.