Physiological and Drug-Induced Fluctuations in Brain Oxygen and Glucose Assessed by Substrateselective Sensors Coupled With High-Speed Amperometry

Kiyatkin, Eugene A.

doi:10.1142/9789811206238_0012

Cited by 7 publications

(3 citation statements)

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“…Our electrochemical measurements revealed that brain oxygen and glucose levels significantly increased following arousing stimulation and showed a significant correlation within the entire duration of responses and their initial components [26] (Fig. 4, Ref.…”

Section: Neural Activation and Peripheral Vasoconstriction As The Factors Determining Intra-brain Fluctuations In Oxygen And Glucosementioning

confidence: 72%

“…Although these studies revealed a basic association of increased CBF with neural activation [22][23][24][25], most techniques used to assess CBF are indirect, have a low temporal resolution, and cannot be used in freely moving animals, especially rats. The development of electrochemical techniques that provide high substrate sensitivity, selectivity, and second-scale temporal resolution made it possible to examine real-time fluctuations of oxygen and glucose in selective brain areas and different body locations in awake, freely moving rats [26]. While assessments of CBF and the tone of cerebral vessels are important for understanding how oxygen and glucose arrive in brain capillaries, it is critically important to know the real-time dynamics of these substances in the brain's extracellular space and their relationships with oxygen changes in peripheral tissues.…”

Section: Neural Activation and Peripheral Vasoconstriction As The Factors Determining Intra-brain Fluctuations In Oxygen And Glucosementioning

confidence: 99%

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Functional role of peripheral vasoconstriction: not only thermoregulation but much more

Kiyatkin

2021

Journal of Integrative Neuroscience

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Peripheral vasoconstriction is a centrally mediated physiological effect known to play an important role in regulating body temperature by adjusting heat exchange with the external environment. However, peripheral vasoconstriction as a component of sympathetic activation also occurs following exposure to various salient stimuli and during motivated behavior at stable environmental temperatures. This review aims to consider available evidence suggesting a significant contribution of this peripheral effect to physiological increases in both brain temperature and entry of oxygen and glucose into the brain's extracellular space. While these effects are triggered by neuronal activation, constriction of blood vessels in the skin and most internal organs results in redistribution of blood from the peripheral to central domains, thus dilating cerebral vessels, increasing global cerebral blood flow, and enhancing the intra-brain entry of oxygen and glucose from arterial blood. This powerful influence appears to determine the long duration of physiological increases in both brain temperature and brain levels of glucose and oxygen and their basic similarity across different brain structures. This work underscores the tight interrelationship between the brain and periphery and a significant contribution of cardiovascular effects in providing the enhanced inflow of oxygen and glucose into brain tissue to prevent metabolic deficit during functional neural activation.

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Section: Neural Activation and Peripheral Vasoconstriction As The Factors Determining Intra-brain Fluctuations In Oxygen And Glucosementioning

confidence: 72%

Section: Neural Activation and Peripheral Vasoconstriction As The Factors Determining Intra-brain Fluctuations In Oxygen And Glucosementioning

confidence: 99%

Functional role of peripheral vasoconstriction: not only thermoregulation but much more

Kiyatkin

2021

Journal of Integrative Neuroscience

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“…Although the hypoxic effects of drugs can be assessed by plethysmography [7,12,13] or pulse oximetry [14][15][16], it is unclear how changes in breathing activity or hemoglobin saturation in blood translate into changes in oxygen levels in the brain's extracellular space-a functionally important parameter that affects the health and survival of neural cells. In contrast to these peripheral measures, oxygen sensors allow direct assessment of real-time fluctuations in brain oxygenation induced by natural stimuli, occurring during motivated behavior, and after exposure of different drugs in freely moving rats under physiologically relevant conditions [11,[17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Xylazine effects on opioid-induced brain hypoxia

Choi

Irwin

Kiyatkin

2023

Preprint

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Xylazine has emerged in recent years as an adulterant in an increasing number of opioid-positive overdose deaths in the United States. Although its exact role in opioid-induced overdose deaths is largely unknown, xylazine is known to depress vital functions and cause hypotension, bradycardia, hypothermia, and respiratory depression. In this study, we examined the brain-specific hypothermic and hypoxic effects of xylazine and its mixtures with fentanyl and heroin in freely moving rats. In the temperature experiment, we found that intravenous xylazine at low, human-relevant doses (0.33, 1.0, 3.0 mg/kg) dose-dependently decreases locomotor activity and induces modest but prolonged brain and body hypothermia. In the electrochemical experiment, we found that xylazine at the same doses dose-dependently decreases nucleus accumbens oxygenation. In contrast to relatively weak and prolonged decreases induced by xylazine, intravenous fentanyl (0.02 mg/kg) and heroin (0.6 mg/kg) induce stronger biphasic brain oxygen responses, with the initial rapid and strong decrease, resulting from respiratory depression, followed by a slower, more prolonged increase reflecting a post-hypoxic compensatory phase, with fentanyl acting much quicker than heroin. The xylazine-fentanyl mixture eliminated the hyperoxic phase of oxygen response and prolonged brain hypoxia, suggesting xylazine-induced attenuation of the brain compensatory mechanisms to counteract brain hypoxia. The xylazine-heroin mixture strongly potentiated the initial oxygen decrease, and the pattern lacked the hyperoxic portion of the biphasic oxygen response, suggesting more robust and prolonged brain hypoxia. These findings suggest that xylazine exacerbates the life-threatening effects of opioids, proposing worsened brain hypoxia as the mechanism contributing to xylazine-positive opioid-overdose deaths.

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