We used Monte Carlo simulations and the diffusion approximation to estimate correction terms for the analysis of reflectance spectra of cortical intrinsic optical signals. These corrections depend on scattering and absorption properties, i.e. they are dependent on assumptions on the tissue blood content and oxygen saturation. The analysis was applied to reflectance spectra acquired during whisker barrel stimulation in the rat where attenuation spectra were converted to changes in oxygenated and deoxygenated haemoglobin concentration. The description of the experimental data as judged by the residual and sensitivity to variations of wavelength was considerably improved when the correction terms were included. Inclusion of the correction does have a considerable impact on the time course of deoxyhaemoglobin concentration changes. In contrast to the calculation without correction terms, there is no indication for an early increase in deoxyhaemoglobin ('early dip'). This finding might further current interpretation of the coupling between neuronal activation and oxygen extraction and supply.
Local and peripheral immune responses are activated after ischemic stroke. In our present study, we investigated the temporal distribution, location, induction, and function of regulatory T cells (Tregs) and the possible involvement of microglia, macrophages, and dendritic cells after middle cerebral artery occlusion (MCAO). C57BL/6J and Foxp3(EGFP) transgenic mice were subjected to 30 minutes MCAO. On days 7, 14, and 30 after MCAO, Tregs and antigen presenting cells were analyzed using fluorescence activated cell sorting multicolor staining and immunohistochemistry. A strong accumulation of Tregs was observed on days 14 and 30 in the ischemic hemisphere accompanied by the elevated presence and activation of microglia. Dendritic cells and macrophages were found on each analyzed day. About 60% of Foxp3(+) Tregs in ischemic hemispheres were positive for the proliferation marker Ki-67 on days 7 and 14 after MCAO. The transfer of naive CD4(+) cells depleted of Foxp3(+) Tregs into RAG1(-/-) mice 1 day before MCAO did not lead to a de novo generation of Tregs 14 days after surgery. After depletion of CD25(+) Tregs, no changes regarding neurologic outcome were detected. The sustained presence of Tregs in the brain after MCAO indicates a long-lasting immunological alteration and involvement of brain cells in immunoregulatory mechanisms.
The coupling of cerebral blood flow (CBF) to neuronal activity is well preserved during evolution. Upon changes in the neuronal activity, an incompletely understood coupling mechanism regulates diameter changes of supplying blood vessels, which adjust CBF within seconds. The physiologic brain tissue oxygen content would sustain unimpeded brain function for only 1 second if continuous oxygen supply would suddenly stop. This suggests that the CBF response has evolved to balance oxygen supply and demand. Surprisingly, CBF increases surpass the accompanying increases of cerebral metabolic rate of oxygen (CMRO 2 ). However, a disproportionate CBF increase may be required to increase the concentration gradient from capillary to tissue that drives oxygen delivery. However, the brain tissue oxygen content is not zero, and tissue pO 2 decreases could serve to increase oxygen delivery without a CBF increase. Experimental evidence suggests that CMRO 2 can increase with constant CBF within limits and decreases of baseline CBF were observed with constant CMRO 2 . This conflicting evidence may be viewed as an oxygen paradox of neurovascular coupling. As a possible solution for this paradox, we hypothesize that the CBF response has evolved to safeguard brain function in situations of moderate pathophysiological interference with oxygen supply. Keywords: brain; CMRO 2 ; functional hyperemia; neurovascular coupling; oxygen A quick glance at basic numbers of oxygen and glucose delivery to the brain and cerebral energy metabolism suggests that the most delicate function of cerebral blood flow (CBF) is the delivery of sufficient amounts of oxygen to the tissue where the oxygen reserve is so low that ATP production declines almost immediately once blood flow ceases. Therefore, the intuitive explanation for the rapid and large CBF response to neuronal activation is the supply of the additional oxygen needed. Experimental observations of large CBF responses accompanying small increases of cerebral metabolic rate of oxygen (CMRO 2 ), however, have cast doubt on this intuitive assumption. A number of alternative hypotheses may reconcile the seemingly conflicting findings: (1) A small increase of CMRO 2 may only be possible with a large increase in CBF due to physical limitations of oxygen delivery. Journal of Cerebral Blood(2) The large CBF response may be necessary to ensure oxygen delivery to the areas most distant from blood supply. (3) The large CBF response may not be necessary in its full extent but may have evolved as a safety mechanism ensuring sufficient oxygen supply in situations where oxygen delivery to the brain is impaired. (4) The large CBF response may be necessary for reasons other than oxygen delivery.In this opinion paper, we discuss studies on brain energy metabolism and neurovascular coupling. Based on the available evidence, we hypothesize that the surprisingly large CBF response to neuronal activation has evolved as a safety mechanism for oxygen delivery. To support this hypothesis, we first review basic facts on ...
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