Alterations In Cerebral Circulation Research Articles

Capillary dysfunction correlates with cortical amyloid load in early Alzheimer's disease

Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer's disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β levels correlated with decreased microvascular blood flow and increased heterogeneity of microvascular blood flow in frontal and temporal areas (p < 0.01). These results indicate a close connection between levels of amyloid-β deposition and brain microvascular perfusion in pAD. A vicious cycle may be established where amyloid-β load and deficiencies in brain perfusion may reinforce each other.

Personalized 0D-1D multiscale hemodynamic modeling and wave dynamics analysis of cerebral circulation for an elderly patient with dementia.

Senile dementia is associated with pronounced alterations in cerebral circulation. A fundamental understanding of intracranial hemodynamics and wave dynamics is essential for assessing dementia risk. Recent findings suggest that higher carotid artery wave intensity (WI) can predict future cognitive impairments in the elderly. However, wave power (WP) is more advantageous for assessing the risk of cognitive impairment and dementia because of its conservative form, which allows quantification of detailed WP distribution among the entire cerebrovascular network. Unfortunately, intracranial hemodynamics and wave dynamics in elderly patients with dementia remain poorly understood due to ethical issues and technical challenges. In this paper, we proposed a novel and easily achievable personalized methodology for the 0D-1D model of cerebral circulation using widely available clinical data on transcranial Doppler ultrasonography velocity, cerebral artery anatomy from magnetic resonance imaging, and brachial artery pressure. Using the proposed model, we simulated the cerebral blood flows and compared the wave dynamics between a healthy elderly subject and one living with dementia. Moreover, we performed a variance-based global sensitivity analysis to quantify the model-predicted WI and WP sensitivity to the uncertainties of model inputs. This provided more precise information for model personalization and further insights into the wave dynamics of cerebral circulation. In conclusion, the proposed personalized model framework provides a practical approach for patient-specific modeling and WI/WP analysis of cerebral circulation through noninvasive clinical data. The wave dynamics features of higher WI and lower WP in cerebral arteries may be an invaluable biomarker for assessing dementia risk.

The Effects of Flumazenil After Midazolam Sedation on Cerebral Blood Flow and Dynamic Cerebral Autoregulation in Healthy Young Males.

It is unknown whether flumazenil antagonizes the decrease in cerebral blood flow or the alteration in dynamic cerebral autoregulation induced by midazolam. We, therefore, investigated the effects on cerebral circulation of flumazenil administered after midazolam, to test our hypothesis that, along with complete reversal of sedation, flumazenil antagonizes the alterations in cerebral circulation induced by midazolam. Sixteen healthy young male subjects received midazolam followed by flumazenil. The modified Observer's Assessment of Alertness/Sedation (OAA/S) scale and bispectral index (BIS) were used to assess levels of sedation/awareness. For evaluation of cerebral circulation, steady-state mean cerebral blood flow velocity (MCBFV) was measured by transcranial Doppler ultrasonography. In addition, dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between mean arterial pressure (MAP) variability and MCBFV variability. During midazolam sedation, defined by an OAA/S score of 3 (responds only after name is called loudly and/or repeatedly), BIS, steady-state MAP, steady-state CBFV, and transfer function gain decreased significantly compared with baseline. After flumazenil administration, an OAA/S score of 5 (responds readily to name spoken in a normal tone) was confirmed. Then, BIS and MAP returned to the same level as baseline. However, steady-state MCBFV showed a further significant decrease compared with that under midazolam sedation, and the decreased transfer function gain persisted. Contrary to our hypothesis, the present results suggest that despite complete antagonism of the sedative effects of midazolam, flumazenil would not reverse the alterations in cerebral circulation induced by midazolam.

MicroRNAs are dysregulated in the cerebral microvasculature of CKD mice

Vascular calcification arises during chronic kidney disease (CKD), and increases the risk of cardiovascular mortality. In CKD, alterations of cerebral circulation were linked with an increase in ischemic strokes and behavioral troubles. Studying pathophysiological mechanisms of calcifications and detecting new biomarkers in the cerebral circulation is thus an important issue. microRNAs are small non-coding, single-stranded RNAs that regulate messenger RNAs at the post-transcriptional level. They are involved in numerous pathologies and represent new opportunities to develop disease predictors. We used RT-qPCR to quantify endothelial-specific microRNAs in cerebral arterioles from WT mice and from pathological models of CKD. We used four mice groups: WT SHAM, WT CKD, Apolipoprotein E Knock-Out (ApoE-KO) SHAM, ApoE-KO CKD. Brains were removed after two and ten weeks of uremia and RNA from cerebral arterioles was extracted. miR-17 and miR-126 were the most dysregulated in the pathological conditions, at both the second week and tenth week of uremia. Our results suggest that miR-17 and miR-126 are potential new biomarkers of cerebral troubles of CKD patients and new therapeutic targets for innovative treatments.

Changes in cerebral circulation and neuronal metabolism during chronic cerebral vasospasm after sub-arachnoid hemorrhage

Development of chronic cerebral vasospasm (VS) after sub-arachnoid hemorrhage (SAH) must be one of the most critical factors influencing morbidity and mortality in patients with ruptured cerebral aneurysm. We studied how neuronal cells are affected by alteration of cerebral circulation and metabolism during VS in a primate model. The SAH was induced in the right basal cisterns in monkeys. Angiography presented VS maximally 7 days after SAH. In the area of VS, cerebral blood flow (CBF) showed a significant reduction accompanied by an impairment of CBF autoregulation from the acute to maximum stage of VS. In this region, cerebral energy metabolism was critically depleted and microcirculation was impaired in a state of impaired CBF autoregulation. The observation by proton magnetic resonance spectroscopy (MRS) in an experimental model demonstrated a small but significant loss of neuronal cells during development of VS. The MRS study in SAH patients also demonstrated the injury in a subpopulation of neurons during development of VS or after SAH. The results indicated that the brain areas of VS are so seriously affected to exist near ischemic threshold, in states of impaired autoregulation. These critical states possibly influence the neuronal cells to survive during development of VS after SAH.

Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat.

Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whether transforming growth factor-alpha (TGF-alpha) was protective in transient focal ischemia and whether alteration of cerebral circulation was involved. Rats received intraventricular TGF-alpha (50 ng, either split into 2 doses given 30 minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood flow was recorded continuously by laser-Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-alpha on arterial tone were assessed in isolated rabbit basilar and common carotid arteries. Transforming growth factor-alpha before and after ischemia reduced infarct volume by 70% at 1 day and 50% at 4 days. Transforming growth factor-alpha given only after ischemia also did reduce infarct volume by 70% at 1 day and 80% at 4 days. The protective effect was more marked in cortex than in striatum. Transforming growth factor-alpha did not change cortical microvascular perfusion and did not modify arterial passive tone nor agonist-induced active tone. It can be concluded that TGF-alpha reduces infarct volume, even when the factor is exclusively administered at reperfusion, and that this effect is not mediated by changes in microvascular perfusion or cerebral arteries. It is therefore suggested that TGF-alpha has a protective effect against neuronal cell death after transient focal ischemia.

Transcephalic electrical impedance provides a means for quantifying pulsatile cerebral blood volume changes following head-up tilt.

Transcephalic electrical impedance (delta Z) was used to assess pulsatile cerebral blood volume changes while tilting nine premature (30-34 weeks) infants 20 degrees head up. High-frequency (1.50-4.00 Hz) delta Z variability decreased 27% while heart rate did not show any change. We would like to suggest that the variability of transcephalic electrical impedance analysed with spectral estimation seems to provide a means for quantifying alterations in cerebral circulation.

Cerebral circulation and function in Cheyne-Stokes respiration

Phasic alterations of cerebral circulation were studied in seventeen patients with Cheyne-Stokes breathing associated with cardiovascular disease, cerebrovascular disease or the obesity cardiorespiratory syndrome. During the hyperpneic phase of respiration, the arterial oxygen saturation was lowest, and the carbon dioxide tension highest, at which time the cerebral arteriovenous oxygen difference was decreased. The converse changes appeared in apnea. An increase in spinal fluid pressure was noted in hyperpnea and a reduction in the circulation time across the brain was also observed. Electroencephalographic abnormalities frequently disappeared during hyperpnea along with improvement in the patient's mental function and consciousness. On the basis of these observations, it is postulated that cyclic alterations in cerebral circulation appear in Cheyne-Stokes respiration with an increased blood flow during hyperpnea and a decreased blood flow in apnea. It appears likely that the phasic alteration in cerebral circulation is the primary factor producing fluctuations in the patient's mental state, electroencephalogram and neurologic signs. It is equally possible, however, that the varying blood flow represents one more manifestation of phasic activity in the central nervous system which may be the basic cause of the syndrome of Cheyne-Stokes respiration.

Cerebral circulation and metabolism in multiple sclerosis; correlative observations by electroencephalography and psychodiagnostic testing.

THE ETIOLOGY and pathologic physiology of multiple sclerosis have remained obscure despite many excellent clinical and pathologic observations. Hypotheses which incriminate vascular spasm and venular thrombosis as factors mechanically responsible for the lesions of multiple sclerosis have incited considerable clinical investigation 1 and have provided the main basis for therapy of acute stages of the disease, namely, the use of so-called cerebral vasodilator drugs and drugs to inhibit formation of vascular thrombi. 2 One of the purposes of the present study, therefore, was to measure cerebral blood flow and metabolism in patients in various stages of multiple sclerosis in an effort to detect the possible presence of alterations in cerebral circulation and metabolism which might presumably be produced by vascular spasm or clotting. Simultaneously, it was hoped to determine whether the known pathological lesions in the brain in multiple sclerosis, whatever their cause, result in measurable alterations in cerebral blood