Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Tissue hypoxia results from an inadequate supply of oxygen (O(2)) that compromises biologic functions. Evidence from experimental and clinical studies increasingly points to a fundamental role for hypoxia in solid tumors. Hypoxia in tumors is primarily a pathophysiologic consequence of structurally and functionally disturbed microcirculation and the deterioration of diffusion conditions. Tumor hypoxia appears to be strongly associated with tumor propagation, malignant progression, and resistance to therapy, and it has thus become a central issue in tumor physiology and cancer treatment. Biochemists and clinicians (as well as physiologists) define hypoxia differently; biochemists define it as O(2)-limited electron transport, and physiologists and clinicians define it as a state of reduced O(2) availability or decreased O(2) partial pressure that restricts or even abolishes functions of organs, tissues, or cells. Because malignant tumors no longer execute functions necessary for homeostasis (such as the production of adequate amounts of adenosine triphosphate), the physiology-based definitions of the term "hypoxia" are not necessarily valid for malignant tumors. Instead, alternative definitions based on clinical, biologic, and molecular effects that are observed at O(2) partial pressures below a critical level have to be applied.

/pdf/tumor-hypoxia-definitions-and-current-clinical-biologic-and-5gkgj1718s.pdf

Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects.

Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 1. General Characteristics.

Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) was studied using multiple sequential administrations of 15O-labeled radiotracers (half-life, 123 sec) and positron emission tomography. In the resting state an excellent correlation (mean r, 0.87) between CBF and CMRO2 was found when paired measurements of CBF and CMRO2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized.

https://www.pnas.org/content/pnas/83/4/1140.full.pdf

Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects.

A biomechanical model is presented for the dynamic changes in deoxyhemoglobin content during brain activation. The model incorporates the conflicting effects of dynamic changes in both blood oxygenation and blood volume. Calculations based on the model show pronounced transients in the deoxyhemoglobin content and the blood oxygenation level dependent (BOLD) signal measured with functional MRI, including initial dips and overshoots and a prolonged poststimulus undershoot of the BOLD signal. Furthermore, these transient effects can occur in the presence of tight coupling of cerebral blood flow and oxygen metabolism throughout the activation period. An initial test of the model against experimental measurements of flow and BOLD changes during a finger-tapping task showed good agreement.

http://ece-research.unm.edu/vcalhoun/courses/fMRI_Spring12/Buxton_1998_dynamics_in_blood_flow.pdf

Dynamics of blood flow and oxygenation changes during brain activation: the balloon model.

Optical fluorescence has an extensive history of application in the laboratory to the measurement of ionic concentrations and the partial pressures of oxygen and carbon dioxide. The use of optical fluorescence based sensors to fulfill a recognized need for continuous invasive monitoring of arterial blood gases offers a number of inherent advantages. However, the requirements placed upon a blood gas probe and supporting instrumentation appropriate for use in the clinical environment result in significant design challenges in selection of suitable fluorescent dyes, maintenance of mechanical integrity while obtaining required miniaturization of sensors, and in the transmission, acquisition, and processing of low level light signals. An optical fluorescence based intravascular blood gas monitoring system has been developed which is particularly suited for the critical care and surgical settings and which has a sensor probe that can be introduced into the patient via a radial artery catheter. This system has shown an excellent agreement of measured with true values of pH, pCO2, and P02 in both in vitro and animal studies. Linear regression analysis of typical in vitro data, where true levels were established via tonometry and standardization to a high accuracy laboratory pH measuring instrument, shows slope/intercept values very close to 1.0/0.0 and correlation coefficients of greater than 0.99 for all three parameters.

Optical Fluorescence and Its Application to an Intravascular Blood Gas Monitoring System

It has been known since 1851 that atmospheric oxygen is taken up by the human epidermis. The contribution to total respiration is negligible. Until now the significance for the local oxygen supply of the skin has remained unknown. With a newly developed sensor, the oxygen fluxoptode, it has become possible to make local measurements of the transcutaneous oxygen flux (tcJO2). In this study the sensor was calibrated so that absolute values of tcJO2 could be reported. At rest, tcJO2 was determined on normal, humidified skin on the volar forearm of 20 volunteers of different age groups. In order to evaluate the contribution of the blood flow to the oxygen supply of the skin, tcJO2 was recorded at the end of a 5 min suprasystolic occlusion of the forearm. At normal skin surface partial oxygen pressure (163 ± 9 Torr), tcJO2 was 0.53 ± 0.27 ml O2 min−1 m−2. A 5 min interruption of blood flow resulted in an increase of 9.5 ± 6.3 % in tcJO2. The value of tcJO2 was unaffected by the age of the subject. Published data on the oxygen diffusion properties of skin and simulations of intracutaneous profiles of oxygen partial pressure indicated that under these conditions, the upper skin layers to a depth of of 0.25–0.40 mm are almost exclusively supplied by external oxygen, whereas the oxygen transport of the blood has a minor influence. As a consequence, a malfunction in capillary oxygen transport cannot be the initiator of the development of superficial skin defects such as those observed in chronic venous incompetence and peripheral arterial occlusive disease.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2001.013067

The cutaneous uptake of atmospheric oxygen contributes significantly to the oxygen supply of human dermis and epidermis

https://www.kidney-international.org/article/S0085-2538(15)47457-5/pdf

Nephron pO2 and renal oxygen usage in the hypertensive rat kidney

Using a newly developed platinum-O2-microeletrode [30] based on the design ofSilver [37] the construction and properties of which are described,pO2-measurements in the parenchyma of the blood-perfused and the cell-free perfused rat kidney were carried out.

The oxygen supply of the rat kidney: measurements of int4arenal pO2.

https://www.kidney-international.org/article/S0085-2538(15)59889-X/pdf

Dietrich W. Lübbers

Papers

Optical Fluorescence and Its Application to an Intravascular Blood Gas Monitoring System

The cutaneous uptake of atmospheric oxygen contributes significantly to the oxygen supply of human dermis and epidermis

Nephron pO2 and renal oxygen usage in the hypertensive rat kidney

The oxygen supply of the rat kidney: measurements of int4arenal pO2.

Heterogeneities and profiles of oxygen pressure in brain and kidney as examples of the pO2 distribution in the living tissue