scholarly journals Topography of Capillary Density, Glucose Metabolism, and Microvascular Function within the Rat Inferior Colliculus

1987 ◽  
Vol 7 (2) ◽  
pp. 154-160 ◽  
Author(s):  
Paul M. Gross ◽  
Nadine M. Sposito ◽  
Susan E. Pettersen ◽  
Diane G. Panton ◽  
Joseph D. Fenstermacher

A midbrain nucleus of the auditory system, the inferior colliculus, was used as a model for analyzing spatial correlations or “coupling” among capillary density, tissue glucose metabolism, and several measures of microvascular function in the rat. The capillary bed of the inferior colliculus was examined with stereological techniques, and physiological measures were obtained with radioactive tracers, quantitative autoradiography, and image processing. Within the colliculus, capillary density, volume fraction, length, and surface area were highest in the central nucleus where the packing densities of neuropil and perikarya are greatest. Rates of glucose metabolism and blood flow correlated closely with capillary density in a 3 × 2 matrix of collicular subregions in the sagittal and coronal planes. The strength of this correlation suggests that estimates of capillary density can be made from measurements of tissue glucose metabolism within this structure under normal conditions. Microvascular blood volume and transcapillary flux of a neutral amino acid, α-aminoisobutyric acid, were homogeneous throughout the colliculus. The studies demonstrate quantitatively in a single brain nucleus a close correspondence between cytoarchitecture, richness of the capillary bed, and complexity of neural activity (inferred from local measures of glucose metabolism and blood flow). Such relationships were suggested by Craigie 67 years ago.

1978 ◽  
Vol 234 (3) ◽  
pp. E248
Author(s):  
A P Shepherd

Earlier reports indicated that arterial hypoxia not only dilated intestinal resistance vessels but also increased capillary filtration coefficients. The latter finding was interpreted as reflecting an increased number of perfused capillaries. Because both increased blood flow and increased capillary density would tend to maintain tissue oxygenation in spite of arterial hypoxia, the main purpose of this paper was to determine how effectively intestinal O2 utilization is maintained during arterial hypoxia. Therefore, I perfused isolated loops of canine small bowel at constant arterial pressure. Under this condition, reducing arterial PO2 to a mean value of 46 +/- 2.4 mmHg caused blood flow to increase to 146% of control, and O2 consumption was kept within 26% of control. In gut loops perfused at constant blood flow, arterial hypoxia depressed O2 uptake still further, but measurements of 86Rb extraction confirmed that the density of the perfused capillary bed increased. Thus, the responses of both resistance and exchange vessels tend to maintain O2 delivery to intestinal tissue during arterial hypoxia.


2015 ◽  
Vol 774 ◽  
pp. 37-66 ◽  
Author(s):  
M. A. Zouache ◽  
I. Eames ◽  
P. J. Luthert

The choriocapillaris is a capillary bed located in a thin layer adjacent to the outer retina and is part of the oxygen delivery system to the photoreceptors of the eye. The blood flow is approximately planar and is serviced by microvessels, which join the choriocapillaris through inlets perpendicular to its plane. Capillaries are densely organised and separated by avascular septal posts, which direct the blood flow. The capillary bed is composed of a juxtaposition of tessellating vascular units called lobules, which are filled and drained independently from each other. A theoretical analysis of the blood flow in an idealised model of a lobule of the choriocapillaris is developed and studied. Lobules are modelled as tessellating polygonal prisms, where the upper and lower surfaces correspond to planar parallel membranes. The septae are modelled as cylinders randomly distributed between the two membranes. Feeding arterioles and draining venules are modelled as inlets and outlets connecting at the lower surface of the prism perpendicularly to the plane of the lobule. An inlet is placed inside the lobule, while an outlet is placed at each of the vertices. The polygonal prism can be formally subdivided into a set of triangular prisms with one inlet and two outlets, each of them located at one of the vertices. The triangular prisms are taken to be isosceles, and are therefore characterised by a vertex angle ${\it\omega}$ at the inlet and a span $L$. The flow is viscously dominated, and is investigated in the lubrication limit, in which the characteristic thickness of the prism is much smaller than the diameter of the cylinders. As a result of the geometry, a stagnation point is located midway between the outlets. A separation streamline joins the inlet and the stagnation point. The pressure drop ${\rm\Delta}\tilde{p}$ and the average fluid particle residence time $\langle \tilde{T}\rangle$ are analysed as a function of the angle at the inlet ${\it\omega}$ and the septae volume fraction ${\it\Phi}$. When no cylinders are present (${\it\Phi}=0$), an analytical expression for the pressure field is calculated by conformal mapping. Close to the triangle walls, the flow is quasi-parallel and characterised by a shorter fluid particle residence time. In the vicinity of the stagnation point, the velocity decreases and the residence time diverges logarithmically with the distance to the stagnation streamline. The minimum in pressure drop corresponds to a maximum in residence time, and is obtained for ${\it\omega}={\rm\pi}/2$. Asymptotic expressions for the pressure drop and average residence time are formulated in both the limits $\Vert {\it\omega}\Vert \ll 1$ and $\Vert {\rm\pi}-{\it\omega}\Vert \ll 1$. The impact of ${\it\Phi}$ on the flow is characterised by solving the equations for the flow numerically and using the Darwin drift framework. We show that the pressure drop is approximately proportional to $1+2{\it\Phi}$ for relatively small ${\it\Phi}$, and that $\langle \tilde{T}\rangle$ is proportional to $1-{\it\Phi}$ regardless of the void fraction or shape of the septae. In the case ${\it\Phi}=0$, the average residence time equals the volume of the domain divided by the volumetric flux. This analysis provides a new perspective on the blood flow dynamics within the choriocapillaris. Lobules form systems, where perfusion and corpuscle transport are a function of the angle that any two venular openings make with an arteriolar opening, the surface area perfused and the void volume fraction. The blood flow velocity and residence time are significantly heterogeneous, which may be responsible for the high degree of selective localisation observed in the pathogenesis of some inflammatory and degenerative diseases of the eye.


2001 ◽  
Vol 14 (5) ◽  
pp. 407-415
Author(s):  
John T. Metz ◽  
Malcolm D. Cooper ◽  
Terry F. Brown ◽  
Leann H. Kinnunen ◽  
Declan J. Cooper

The process of discovering and developing new drugs is complicated. Neuroimaging methods can facilitate this process. An analysis of the conceptual bases and practical limitations of different neuroimaging modalities reveals that each technique can best address different kinds of questions. Radioligand studies are well suited to preclinical and Phase II questions when a compound is known or suspected to affect well-understood mechanisms; they are also useful in Phase IV to characterize effective agents. Cerebral blood flow studies can be extremely useful in evaluating the effects of a drug on psychological tasks (mostly in Phase IV). Glucose metabolism studies can answer the simplest questions about whether a compound affects the brain, where, and how much. Such studies are most useful in confirming central effects (preclinical and early clinical phases), in determining effective dose ranges (Phase II), and in comparing different drugs (Phase IV).


1999 ◽  
Vol 82 (1) ◽  
pp. 164-175 ◽  
Author(s):  
Kevin A. Davis ◽  
Ramnarayan Ramachandran ◽  
Bradford J. May

Single units in the central nucleus of the inferior colliculus (ICC) of unanesthetized decerebrate cats can be grouped into three distinct types (V, I, and O) according to the patterns of excitation and inhibition revealed in contralateral frequency response maps. This study extends the description of these response types by assessing their ipsilateral and binaural response map properties. Here the nature of ipsilateral inputs is evaluated directly using frequency response maps and compared with results obtained from methods that rely on sensitivity to interaural level differences (ILDs). In general, there is a one-to-one correspondence between observed ipsilateral input characteristics and those inferred from ILD manipulations. Type V units receive ipsilateral excitation and show binaural facilitation (EE properties); type I and type O units receive ipsilateral inhibition and show binaural excitatory/inhibitory (EI) interactions. Analyses of binaural frequency response maps show that these ILD effects extend over the entire receptive field of ICC units. Thus the range of frequencies that elicits excitation from type V units is expanded with increasing levels of ipsilateral stimulation, whereas the excitatory bandwidth of type I and O units decreases under the same binaural conditions. For the majority of ICC units, application of bicuculline, an antagonist for GABAA-mediated inhibition, does not alter the basic effects of binaural stimulation; rather, it primarily increases spontaneous and maximum discharge rates. These results support our previous interpretations of the putative dominant inputs to ICC response types and have important implications for midbrain processing of competing free-field sounds that reach the listener with different directional signatures.


2021 ◽  
Vol 18 (2) ◽  
pp. 147916412199903
Author(s):  
Laura Croteau ◽  
Clément Mercier ◽  
Étienne Fafard-Couture ◽  
Alexandre Nadeau ◽  
Stéphanie Robillard ◽  
...  

Aims: Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling. Methods: Nondiabetic and diabetic mice, with ( ec-Prkcd−/−) or without ( ec-Prkcdf/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs. Results: Ischemic muscle of diabetic ec-Prkcdf/f mice exhibited reduced blood flow reperfusion and capillary density while apoptosis increased as compared to nondiabetic ec-Prkcdf/f mice. In contrast, blood flow reperfusion and capillary density were significantly improved in diabetic ec-Prkcd−/− mice. VEGF signaling pathway was restored in diabetic ec-Prkcd−/− mice. The deletion of PKCδ in ECs prevented diabetes-induced VEGF unresponsiveness through a reduction of SHP-1 phosphatase activity. Conclusions: Our data provide new highlights in mechanisms by which PKCδ activation in EC contributed to poor collateral vessel formation, thus, offering novel therapeutic targets to improve angiogenesis in the diabetic limb.


1996 ◽  
Vol 270 (5) ◽  
pp. H1696-H1703 ◽  
Author(s):  
D. Mitchell ◽  
K. Tyml

Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 micron(s) from the feeding arteriole) reduced red blood cell (RBC) velocity [VRBC; control VRBC = 238 +/- 58 (SE) micron/s; delta VRBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (Dcon = 6.3 +/- 0.7 micron, delta D = 5 +/- 7%) or draining venule diameter (Dcon = 10.1 +/- 0.6 micron, delta D = 4 +/- 2%). Because of the VRBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 micron capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 micron. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary VRBC. Bradykinin (BK) locally applied to the capillary caused significant increases in VRBC (delta VRBC = 111 +/- 23%) and in arteriolar diameter (delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (delta VRBC = -4 +/- 27%; delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.


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