Long-Term Adaptation of Cerebral Hemodynamic Response to Somatosensory Stimulation during Chronic Hypoxia in Awake Mice

Effects of chronic hypoxia on hemodynamic response to sensory stimulation were investigated. Using laser-Doppler flowmetry, change in cerebral blood flow ( CBF) was measured in awake mice, which were housed in a hypoxic chamber (8% O2) for 1 month. The degree of increase in CBF evoked by sensory stimulation was gradually decreased over 1 month of chronic hypoxia. No significant reduction of increase in CBF induced by hypercapnia was observed during 1 month. Voltage-sensitive dye (VSD) imaging of the somatosensory cortex showed no significant decrease in neural activation over 1 month, indicating that the reduction of increase in CBF to sensory stimulation was not caused by cerebrovascular or neural dysfunction. The simulation study showed that, when effective diffusivity for oxygen in the capillary bed ( D) value increases by chronic hypoxia due to an increase in capillary blood volume, an increase in the cerebral metabolic rate of oxygen utilization during neural activation can occur without any increase in CBF. Although previous study showed no direct effects of acute hypoxia on CBF response, our finding showed that hemodynamic response to neural activation could be modified in response to a change in their balance to energy demand using chronic hypoxia experiments.

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Pial Arteries Respond Earlier than Penetrating Arterioles to Neural Activation in the Somatosensory Cortex in Awake Mice Exposed to Chronic Hypoxia: An Additional Mechanism to Proximal Integration Signaling?

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.140 ◽

2014 ◽

Vol 34 (11) ◽

pp. 1761-1770 ◽

Cited By ~ 14

Author(s):

Yuta Sekiguchi ◽

Hiroyuki Takuwa ◽

Hiroshi Kawaguchi ◽

Takahiro Kikuchi ◽

Eiji Okada ◽

...

Keyword(s):

Chronic Hypoxia ◽

Temporal Dynamics ◽

Neural Activation ◽

Additional Mechanism ◽

Pial Arteries ◽

Doppler Flowmetry ◽

Pial Artery ◽

Mouse Cortex ◽

Longitudinal Effects ◽

Whisker Stimulation

The pial and penetrating arteries have a crucial role in regulating cerebral blood flow (CBF) to meet neural demand in the cortex. Here, we examined the longitudinal effects of chronic hypoxia on the arterial diameter responses to single whisker stimulation in the awake mouse cortex, where activity-induced responses of CBF were gradually attenuated. The vasodilation responses to whisker stimulation under prehypoxia normal conditions were 8.1% and 12% relative to their baselines in the pial arteries and penetrating arterioles, respectively. After 3 weeks of hypoxia, however, these responses were significantly reduced to 5.5% and 4.1%, respectively. The CBF response, measured using laser-Doppler flowmetry (LDF), induced by the same whisker stimulation was also attenuated (14% to 2.6%). A close linear correlation was found for the responses between the penetrating arteriolar diameter and LDF, and their temporal dynamics. After 3 weeks of chronic hypoxia, the initiation of vasodilation in the penetrating arterioles was significantly extended, but the pial artery responses remained unchanged. These results show that vasodilation of the penetrating arterioles followed the pial artery responses, which are not explainable in terms of proximal integration signaling. The findings therefore indicate an additional mechanism for triggering pial artery dilation in the neurovascular coupling.

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Tickling Expectations: Neural Processing in Anticipation of a Sensory Stimulus

Journal of Cognitive Neuroscience ◽

10.1162/089892900562318 ◽

2000 ◽

Vol 12 (4) ◽

pp. 691-703 ◽

Cited By ~ 132

Author(s):

Katrina Carlsson ◽

Predrag Petrovic ◽

Stefan Skare ◽

Karl Magnus Petersson ◽

Martin Ingvar

Keyword(s):

Sensory Input ◽

Sensory Stimulation ◽

Stimulus Onset ◽

Essential Elements ◽

Anterior Cingulate ◽

Sensory Stimulus ◽

Neural Activation ◽

Somatosensory Stimulation ◽

Somatosensory Stimulus ◽

The Right

Predictions of the near future can optimize the accuracy and speed of sensory processing as well as of behavioral responses. Previous experience and contextual cues are essential elements in the generation of a subjective prediction. Using a blocked fMRI paradigm, we investigated the pattern of neural activation in anticipation of a sensory stimulus and during the processing of the somatosensory stimulus itself. Tickling was chosen as the somatosensory stimulus rather than simple touch in order to increase the probability to get a high degree of anticipation. The location and nature of the stimulus were well defined to the subject. The state of anticipation was initiated by attributing an uncertainty regarding the time of stimulus onset. The network of activation and deactivation during anticipation of the expected stimulus was similar to that engaged during the actual sensory stimulation. The areas that were activated during both states included the contralateral primary sensory cortex, bilateral areas in the inferior parietal lobules, the putative area SII, the right anterior cingulate cortex and areas in the right prefrontal cortex. Similarly, common decreases were observed in areas of sensorimotor cortex located outside the area representing the target of stimulus, i.e., areas that process information which is irrelevant to the attended process. The overlapping pattern of change, during the somatosensory stimulation and the anticipation, furthers the idea that predictions are subserved by a neuronal network similar to that which subserves the processing of actual sensory input. Moreover, this study indicates that activation of primary somatosensory cortex can be obtained without intra-modal sensory input. These findings suggest that anticipation may invoke a tonic top-down regulation of neural activity.

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Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.4.1748 ◽

1993 ◽

Vol 75 (4) ◽

pp. 1748-1757 ◽

Cited By ~ 77

Author(s):

V. Hampl ◽

S. L. Archer ◽

D. P. Nelson ◽

E. K. Weir

Keyword(s):

Pulmonary Hypertension ◽

Arterial Pressure ◽

Chronic Hypoxia ◽

Acute Hypoxia ◽

Systemic Blood Pressure ◽

Systemic Circulation ◽

Systemic Arterial Pressure ◽

Hypoxic Pulmonary Hypertension ◽

Basal Tone ◽

Isolated Lungs

It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.

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Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways

Cell Death and Disease ◽

10.1038/s41419-021-04351-x ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Ruzhou Zhao ◽

Xingcheng Zhao ◽

Xiaobo Wang ◽

Yanqi Liu ◽

Jie Yang ◽

...

Keyword(s):

Acute Hypoxia ◽

Survival Rates ◽

The Body ◽

Utilization Efficiency ◽

Ros Generation ◽

Oxygen Utilization ◽

Mtor Inhibition ◽

Atp Production ◽

Hypoxic Adaptation ◽

Hypoxic Tolerance

AbstractRapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.

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Improvement of Gait in Patients with Stroke Using Rhythmic Sensory Stimulation: A Case-Control Study

Journal of Clinical Medicine ◽

10.3390/jcm11020425 ◽

2022 ◽

Vol 11 (2) ◽

pp. 425

Author(s):

Yungon Lee ◽

Sunghoon Shin

Keyword(s):

Sensory Stimulation ◽

Chronic Stroke ◽

Gait Variability ◽

Healthy Controls ◽

Normal Walking ◽

Somatosensory Stimulation ◽

Stroke Group ◽

And Gender ◽

Reduced Mobility ◽

Control Study

Patients with stroke suffer from impaired locomotion, exhibiting unstable walking with increased gait variability. Effects of rhythmic sensory stimulation on unstable gait of patients with chronic stroke are unclear. This study aims to determine the effects of rhythmic sensory stimulation on the gait of patients with chronic stroke. Twenty older adults with stroke and twenty age- and gender-matched healthy controls walked 60 m under four conditions: normal walking with no stimulation, walking with rhythmic auditory stimulation (RAS) through an earphone in the ear, walking with rhythmic somatosensory stimulation (RSS) through a haptic device on the wrist of each participant, and walking with rhythmic combined stimulation (RCS: RAS + RSS). Gait performance in the stroke group significantly improved during walking with RAS, RSS, and RCS compared to that during normal walking (p < 0.008). Gait variability significantly decreased under the RAS, RSS, and RCS conditions compared to that during normal walking (p < 0.008). Rhythmic sensory stimulation is effective in improving the gait of patients with chronic stroke, regardless of the type of rhythmic stimuli, compared to healthy controls. The effect was greater in patients with reduced mobility, assessed by the Rivermead Mobility Index (RMI).

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Specific mitochondrial adaptation to chronic hypoxia counteracts effects of acute hypoxia in perfused rats beating hearts

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1184.2 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Veronique Deschodt‐Arsac ◽

Guillaume Calmettes ◽

Fanny Vaillant ◽

Mathilde Chapolard ◽

Bernard Muller ◽

...

Keyword(s):

Chronic Hypoxia ◽

Acute Hypoxia ◽

Mitochondrial Adaptation

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Chronic Hypoxia Enhances β-Oxidation-Dependent Electron Transport via Electron Transferring Flavoproteins

Cells ◽

10.3390/cells8020172 ◽

2019 ◽

Vol 8 (2) ◽

pp. 172 ◽

Cited By ~ 2

Author(s):

Dominik C. Fuhrmann ◽

Catherine Olesch ◽

Nina Kurrle ◽

Frank Schnütgen ◽

Sven Zukunft ◽

...

Keyword(s):

Oxygen Consumption ◽

Fatty Acid ◽

Electron Transport ◽

Mitochondrial Respiration ◽

Chronic Hypoxia ◽

Acute Hypoxia ◽

Acid Synthesis ◽

Acid Oxidation ◽

Fatty Acid Production ◽

Consumption Rates

Hypoxia poses a stress to cells and decreases mitochondrial respiration, in part by electron transport chain (ETC) complex reorganization. While metabolism under acute hypoxia is well characterized, alterations under chronic hypoxia largely remain unexplored. We followed oxygen consumption rates in THP-1 monocytes during acute (16 h) and chronic (72 h) hypoxia, compared to normoxia, to analyze the electron flows associated with glycolysis, glutamine, and fatty acid oxidation. Oxygen consumption under acute hypoxia predominantly demanded pyruvate, while under chronic hypoxia, fatty acid- and glutamine-oxidation dominated. Chronic hypoxia also elevated electron-transferring flavoproteins (ETF), and the knockdown of ETF–ubiquinone oxidoreductase lowered mitochondrial respiration under chronic hypoxia. Metabolomics revealed an increase in citrate under chronic hypoxia, which implied glutamine processing to α-ketoglutarate and citrate. Expression regulation of enzymes involved in this metabolic shunting corroborated this assumption. Moreover, the expression of acetyl-CoA carboxylase 1 increased, thus pointing to fatty acid synthesis under chronic hypoxia. Cells lacking complex I, which experienced a markedly impaired respiration under normoxia, also shifted their metabolism to fatty acid-dependent synthesis and usage. Taken together, we provide evidence that chronic hypoxia fuels the ETC via ETFs, increasing fatty acid production and consumption via the glutamine-citrate-fatty acid axis.

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Functional and structural changes with hypoxia in pulmonary circulation of spontaneously hypertensive rats

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.3.1101 ◽

1994 ◽

Vol 77 (3) ◽

pp. 1101-1107 ◽

Cited By ~ 22

Author(s):

S. P. Janssens ◽

B. T. Thompson ◽

C. R. Spence ◽

C. A. Hales

Keyword(s):

Pulmonary Hypertension ◽

Arterial Pressure ◽

Vascular Remodeling ◽

Spontaneously Hypertensive Rats ◽

Structural Changes ◽

Chronic Hypoxia ◽

Acute Hypoxia ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

Chronic hypoxic pulmonary hypertension involves both vasoconstriction and vascular remodeling. Spontaneously hypertensive rats (SHR) have an increased systemic vascular resistance and a greater responsiveness to constricting stimuli. We hypothesized that, in contrast to age-matched normotensive Wistar-Kyoto rats (WKY), SHR also display spontaneous pulmonary hypertension in normoxia and increased vascular response to acute and chronic hypoxia. Baseline mean pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR) were higher in SHR than in WKY. With acute hypoxia (10% O2 for 15 min), PAP increased to the same extent in SHR and WKY and cardiac output (CO) was unchanged in WKY but increased in SHR. Thus, the rise in PAP in the SHR might be accounted for by the rise in CO, as TPR did not rise, but not that in the WKY, as TPR increased. After 12 days in hypoxia (10% O2), mean arterial pressure was unchanged in WKY but decreased significantly in SHR without a change in CO. PAP increased by 59% in SHR and 54% in WKY when the rats were taken from the hypoxic chamber for 1 h. Acute hypoxic challenge caused a further increase in PAP only in WKY. Medial wall thickness of alveolar duct and terminal bronchial vessels was similar in WKY and SHR after chronic hypoxia. We conclude that SHR exhibit mild baseline pulmonary hypertension in normoxia and that chronic hypoxia does not produce a disproportionate increase in SHR pulmonary vascular remodeling and pulmonary hypertension.

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Plasma angiotensin II levels in hypoxic and hypovolemic stress in unanesthetized rabbits

Journal of Applied Physiology ◽

10.1152/jappl.1976.41.4.462 ◽

1976 ◽

Vol 41 (4) ◽

pp. 462-465 ◽

Cited By ~ 34

Author(s):

R. M. Zakheim ◽

A. Molteni ◽

L. Mattioli ◽

M. Park

Keyword(s):

Angiotensin Ii ◽

Plasma Levels ◽

Chronic Hypoxia ◽

Normal Values ◽

Acute Hypoxia ◽

Temporary Increase ◽

Hypoxic Stress ◽

Renin Angiotensin Aldosterone System ◽

Plasma Angiotensin ◽

Stress Bleeding

Plasma levels of angiotensin II were determined by radioimmunoassay in unanesthetized white rabbits exposed to acute hypoxia (FIO2 10% for 10 min),chronic hypoxia (0.5 atm up to 16 days), or hypovolemic stress (bleeding 20ml/kg). Angiotensin II levels significantly decreased after 10 min of acutehypoxia in normal rabbits and significantly increased when the same procedure was applied to animals previously exposed to hypoxia by 6–8 days of permanence in the hypobaric chamber or sodium deprivation. Chronic hypoxia resulted in a temporary increase of angiotensin II already evident on the 3rd day, but maximal at the 9th day with return to normal values within 16 days.Hypovolemic stress resulted in the expected rise of angiotensin II levels 10 min postbleeding both in normal and acclimatized rabbits. The responseof the renin-angiotensin-aldosterone system to hypoxic and hypovolemic stress is different. The direction and magnitude of the response to hypoxia depends on the underlying state of activation of the system and the cardiovascular condition of the animal at the time of hypoxic stress.

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Somatosensory Processing in the Human Inferior Prefrontal Cortex

Journal of Neurophysiology ◽

10.1152/jn.2002.88.3.1400 ◽

2002 ◽

Vol 88 (3) ◽

pp. 1400-1406 ◽

Cited By ~ 38

Author(s):

Matthew C. Hagen ◽

David H. Zald ◽

Tricia A. Thornton ◽

José V. Pardo

Keyword(s):

Inferior Frontal Gyrus ◽

Sensory Stimulation ◽

Brain Regions ◽

Somatosensory Processing ◽

Somatosensory Stimulation ◽

Tactile Stimuli ◽

Somatosensory Cortices ◽

Frontal Operculum ◽

Frontal Activity ◽

Ventral Area

Three inferior prefrontal regions in the monkey receive afferents from somatosensory cortices: the orbitofrontal cortex (OFC), the ventral area of the principal sulcus, and the anterior frontal operculum. To determine whether these areas show responses to tactile stimuli in humans, we examined data from an ongoing series of PET studies of somatosensory processing. Unlike previous work showing ventral frontal activity to hedonic (pleasant/unpleasant) sensory stimulation, the tactile stimuli used in these studies had a neutral hedonic valence. Our data provide evidence for at least two discrete ventral frontal brain regions responsive to somatosensory stimulation: 1) the posterior inferior frontal gyrus (IFG) and adjacent anterior frontal operculum, and 2) the OFC. The former region (posterior IFG/anterior frontal operculum) may have a more specific role in attending to tactile stimuli.

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