Cortical Capillary Blood Flow Research Articles

Pathogenic soluble tau peptide disrupts endothelial calcium signaling and vasodilation in the brain microvasculature

The accumulation of the microtubule-associated tau protein in and around blood vessels contributes to brain microvascular dysfunction through mechanisms that are incompletely understood. Delivery of nutrients to active neurons in the brain relies on capillary calcium (Ca2+) signals to direct blood flow. The initiation and amplification of endothelial cell Ca2+ signals require an intact microtubule cytoskeleton. Since tau accumulation in endothelial cells disrupts native microtubule stability, we reasoned that tau-induced microtubule destabilization would impair endothelial Ca2+ signaling. We tested the hypothesis that tau disrupts the regulation of local cerebral blood flow by reducing endothelial cell Ca2+ signals and endothelial-dependent vasodilation. We used a pathogenic soluble tau peptide (T-peptide) model of tau aggregation and mice with genetically encoded endothelial Ca2+ sensors to measure cerebrovascular endothelial responses to tau exposure. T-peptide significantly attenuated endothelial Ca2+ activity and cortical capillary blood flow in vivo. Further, T-peptide application constricted pressurized cerebral arteries and inhibited endothelium-dependent vasodilation. This study demonstrates that pathogenic tau alters cerebrovascular function through direct attenuation of endothelial Ca2+ signaling and endothelium-dependent vasodilation.

Effect of iodinated contrast media on the oxygen tension in the renal cortico-medullary region of pigs.

Repeated injections of iodinated contrast media (CM) can lead to a deterioration of the renal blood flow, can redistribute blood from the renal cortex to other parts of the kidney and can cause small decreases of the blood flow in cortical capillaries, a significant reduction in blood flow in peritubular capillaries and a significant reduction in blood flow in the vasa recta. Therefore, a study in pigs was designed, to show whether the repeated injection of CM boli, alone, can cause a reduction of oxygenation in the cortico-medullar renal tissue - the region with the highest oxygen demand in the kidney - of pigs.While the mean pO2-value had only decreased by 0.3 mmHg from 29.9±4.3 mmHg to 29.6±4.3 mmHg (p = 0.8799) after the tenth Iodixanol bolus, it decreased by 5.9 mmHg from 34.0±4.3 mmHg to 28.1±4.3 mmHg after the tenth Iopromide bolus (p = 0.044). This revealed a remarkable difference in the influence of these CM on the oxygen partial pressure in the kidney.Repeated applications of CM had a significant influence on the renal oxygen partial pressure. In line with earlier studies showing a redistribution of blood from the cortex to other renal areas, this study revealed that Iodixanol - in contrast to Iopromide - induced no changes in the pO2 in the cortico-medullar region which confirms that Iodixanol did not hinder the flow of blood through the renal micro-vessels. These results are in favor of a hypothesis from Brezis that a microcirculatory disorder might be the basis for the development of CI-AKI.

The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES).

BackgroundKidney transplantation is the therapy of choice for end-stage kidney disease. Graft’s life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term.Patients and MethodsRT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction.ResultsThe CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p<0.001). Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12 (54.5 ± 28.2 vs 33.7 ± 30 dB/sec, living vs brain-death donor, respectively, p = 0.004) despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term.ConclusionRT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions.

Stalled blood flow in cortical capillaries, caused by recurrent plugging by leukocytes, contributes to brain blood flow reductions in mouse models of Alzheimer's disease

Stalled blood flow in cortical capillaries, caused by recurrent plugging by leukocytes, contributes to brain blood flow reductions in mouse models of Alzheimer's disease

Chronic optical access through a polished and reinforced thinned skull

We present a method to form an optical window in the mouse skull that spans millimeters and is stable for months without inflammation of the brain. This enabled us to repeatedly image blood flow in cortical capillaries of awake animals and determine long-range correlations in speed. We further demonstrate repeated cortical imaging of dendritic spines, microglia, and angioarchitecture, as well as illumination to drive motor output via optogenetics and induce microstrokes via photosensitizers.

Ultrasonography in kidney transplantation: values and new developments

Renal transplant is performed on patients with end-stage renal disease. Gray-scale renal sonography combined with color Doppler has become the main noninvasive imaging method for evaluating a kidney transplant, as it provides information about the kidney anatomy and its vascular flow. In this article, we discuss the utility of sonography in renal transplants and describe the ultrasound findings in early and chronic graft pathology. Also, we explain new developments in ultrasound imaging with contrast media and its utility in renal transplantation, proposing that contrast-enhanced sonography be incorporated as a method to evaluate graft status because of its capability to evaluate cortical capillary blood flow.

Temperature and hemodynamic changes associated with increased neural damage to global hemispheric hypoxic ischemia by prior prostaglandin E2,D2and F2αadministration

Experiments compared the hemispheric neural damage resulting from global hemispheric hypoxic ischemia (GHHI, ligation of right common carotid artery plus 35min of 12% O2) in groups of anesthetized, male Long Evans rats, 9–10 weeks of age, kept at 37°C, and previously given an intracerebroventricular (i.c.v., 2.5μl) injection of 28 or 70 pmoles of PGE2, PGF2αor PGD2or sterile saline (SS) 30 min beforehand. Mean arterial pressure (MAP), ipsilateral cortical capillary blood flow (CBF), colonic (Tc), ipsilateral (Tipsi) and contralateral (Tcontra), temporalis muscle temperatures were measured before, during and for 15 min after GHHI. Necrotic neural damage was assessed 7 days post-GHHI. All groups given GHHI + PGs showed increased ipsilateral hemispheric damage to GHHI especially due to enhanced neocortical damage, compared to the saline control group given the same insult. PGD2was the most potent PG to cause further damage to the global insult. Tc, Tipsi, Tcontraand MAP increased following the i.c.v. injection of PGE2. Icv PGF2αtransiently decreased MAP, PGD2tended to decrease cerebral blood flow and neither evoked changes in temperature compared to respective pre-injection control values. Results demonstrate increased neural damage to GHHI with prior icv PGE2, PGF2αor PGD2administration.

The effect of head cooling on the physiological responses and resultant neural damage to global hemispheric hypoxic ischemia in prostaglandin E 2 treated rats

The study determined if head cooling would reduce the augmented increase in neural damage of global hemispheric hypoxic ischemia (GHHI) of prostaglandin E 2 (PGE 2) treated rats. Halothane anesthetized, male, Long–Evans rats (9–11 weeks of age), kept at 37°C colonically ( T c) had (a) systemic core (colonic, T c), temporalis muscle temperatures ipsilateral ( T ipsi) and contralateral ( T contra) to the side of right common carotid artery (RCCA) ligation, (b) mean arterial pressure (MAP) and (c) ipsilateral cortical capillary blood flow (CBF) measured simultaneously after intracerebroventricular (i.c.v.) injection (2.5 μl) of sterile (SS) or 25 ng PGE 2 then GHHI (35 min of 12% O 2, balance N 2 after RCCA ligation) followed by a 10 min normoxic recovery period. Head cooling (10°C cool air over the head region) occurred in one PGE 2 subgroup 10 min post-injection until the end of the hypoxic period. Icv-PGE 2 treated rats, maintained at 37°C (no head cooling) had increased T c, T ipsi, T contras and MAPs from respective pre-injection control values; this group showed increased ipsilateral hemispheric neural damage to GHHI assessed 7 days later, compared to i.c.v.-SS treated group given the same GHHI insult. Cooling the head region of rats previously given PGE 2 decreased T ipsi and T contras from respective control temperatures but did not change MAP or CBF from respective pre-injection values. Hemispheric damage of the PGE 2 cooled group was reduced from damage of non-cooled PGE 2 treated rats and was similar to i.c.v.-SS treated rats. Results demonstrate that the heightened core temperatures induced by PGE 2 administration (major endogenous mediator of bacterial fever induction) play a significant role in escalating the neural damage to global ischemia.