Cerebral Blood Flow Dysregulation Research Articles

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2cc) compared to those without renal insufficiency (110.5 ± 93.2cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (β = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

Amyloid Beta-Mediated Neurovascular Toxicity in Alzheimer's Disease.

The brain vascular system receives one-fifth of the total oxygen from the cardiac output, and this transport system is highly dependent on blood-brain barrier (BBB) integrity. The cerebral blood flow is controlled by neurovascular coupling through neurovascular units (NVUs). The NVU includes different types of cells, such as mural cells, astrocytes, pericytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs). The cellular composition of NVU varies throughout the vascular tree. Amyloid β (Aβ) is abundantly present in the central nervous system, but the pathological accumulation of misfolded Aβ protein causes vascular damage, resulting in neurovascular dysfunction. Aβ aggregation can activate the astrocytes and endothelial cells. It is followed by pericyte degeneration which results in dysregulation of cerebral blood flow (CBF), neurovascular uncoupling, and BBB breakdown. Thus, understanding the cellular and molecular mechanisms of Aβ-induced neurovascular toxicity is crucial for determining normal and diseased brain function. This chapter discusses the components of NVU, neurovascular uncoupling, Aβ-induced cerebrovascular reactivity, and cerebral blood flow reduction in neurodegenerative disorders, with special emphasis on Alzheimer's disease.

CHRONIC CEREBRAL ISCHEMIA. MODERN VIEW OF THE PROBLEM

Introduction. Chronic cerebral ischemia (CCI) is considered a syndrome that develops as a result of a slowly progressive reduction in cerebral blood flow. This reduction occurs due to the gradual accumulation of ischemic and secondary degenerative changes in the brain, which are caused by repeated ischemic episodes resulting from the development of atherosclerosis and arterial hypertension. These changes lead to impairment of brain functions, manifested by progressive neurological, neuropsychological, and mental disorders.
 The aim. To analyze the problems of pathogenesis, diagnosis, and treatment of CCI from the sources of modern literature in order to optimize the treatment of this group of patients.
 Materials and methods. Bibliosemantic, comparative and method of system analysis.
 Results. The pathogenetic mechanisms underlying CCI remain controversial due to the heterogeneity of causes and the complexity of the neuropathology associated with the disease. However, one common reason that can be named is dysregulation of cerebral blood flow, that results in chronic cerebral hypoperfusion, which can lead to the development of vascular cognitive impairment and dementia. Detection of biological markers in the patients' blood in combination with neuropsychological testing, neurophysiological (CEP P300, EEG) and neuroimaging (CT, MRI, Doppler Ultrasound of the head and neck) methods, which confirms the morphological substrate of vascular disease (leukoareosis, focal changes, multi-infarct condition, cerebral atrophy) and provides the possibility of choosing an effective pathogenetically-justified treatment.
 Conclusions. The rating of effectiveness of treatment in CCI is complicated considering difficulties in the selection of the efficiency criteria due to the significant differences in the methodology and research formats, as well as problem of a significant medication-related burden in the case of comorbidities. In this regard, the main direction in therapy is combined neuroprotection, which allows to optimize the possibilities of this strategy and to increase its clinical significance in angioneurology.

Neuroprotective Effect of Platinum Nanoparticles Is Not Associated with Their Accumulation in the Brain of Rats.

Platinum nanoparticles (nPts) have neuroprotective/antioxidant properties, but the mechanisms of their action in cerebrovascular disease remain unclear. We investigated the brain bioavailability of nPts and their effects on brain damage, cerebral blood flow (CBF), and development of brain and systemic oxidative stress (OS) in a model of cerebral ischemia (hemorrhage + temporary bilateral common carotid artery occlusion, tBCAO) in rats. The nPts (0.04 g/L, 3 ± 1 nm diameter) were administered to rats (N = 19) intraperitoneally at the start of blood reperfusion. Measurement of CBF via laser Doppler flowmetry revealed that the nPts caused a rapid attenuation of postischemic hypoperfusion. The nPts attenuated the apoptosis of hippocampal neurons, the decrease in reduced aminothiols level in plasma, and the glutathione redox status in the brain, which were induced by tBCAO. The content of Pt in the brain was extremely low (≤1 ng/g). Thus, nPts, despite the extremely low brain bioavailability, can attenuate the development of brain OS, CBF dysregulation, and neuronal apoptosis. This may indicate that the neuroprotective effects of nPts are due to indirect mechanisms rather than direct activity in the brain tissue. Research on such mechanisms may offer a promising trend in the treatment of acute disorders of CBF.

Cerebroprotective actions of hydrogen sulfide in the epileptic brain in newborn pigs.

Neonatal epileptic seizures cause postictal dysregulation of cerebral blood flow. Hydrogen sulfide (H2S), a mediator with vasodilator and antioxidant properties, is produced in the brain by astrocyte cystathionine β-synthase (CBS). This study investigated whether H2S improves the cerebral vascular outcome of seizures. Epileptic seizures were induced in newborn pigs using bicuculline. The effects of the CBS inhibitor aminooxyacetate (AOA) and the H2S donor NaHS on cerebral vascular outcome of seizures were examined in live pigs, cerebral endothelial cells, and cortical astrocytes. Brain H2S was elevated during seizures. AOA blocked H2S and reduced functional hyperemia in the epileptic brain. The endothelium- and astrocyte-dependent vasodilation of pial arterioles was impaired 48 h after seizures suggesting cerebral vascular dysfunction. Systemic NaHS elevated brain H2S and blocked reactive oxygen species in the epileptic brain and in primary endothelial cells and astrocytes during inflammatory and excitotoxic conditions. Postictal cerebrovascular dysfunction was exaggerated in H2S-inhibited pigs and minimized in NaHS-treated pigs. H2S elevation in the epileptic brain via activation of CBS contributes to functional hyperemia and exhibits cerebroprotective properties. The H2S donor NaHS enhances brain antioxidant defense and provides a therapeutic approach for preventing adverse cerebral vascular outcome of neonatal epileptic seizures. Epileptic seizures in neonates lead to prolonged postictal cerebral vascular dysregulation. The role of hydrogen sulfide (H2S), a mediator with vasodilator and antioxidant properties, in the epileptic brain has been explored. Astrocytes are major sites of enzymatic H2S production in the epileptic brain. Postictal cerebral vascular dysfunction is exaggerated when astrocyte H2S production is pharmacologically inhibited during seizures. Postictal cerebral vascular dysfunction is minimized when the brain H2S is elevated by systemic administration of NaHS during seizures. NaHS provides a therapeutic approach for improving cerebrovascular outcome of epileptic seizures via a mechanism that involves the antioxidant potential of H2S.

A Study on the Pathogenesis of Vascular Cognitive Impairment and Dementia: The Chronic Cerebral Hypoperfusion Hypothesis.

The pathogenic mechanisms underlying vascular cognitive impairment and dementia (VCID) remain controversial due to the heterogeneity of vascular causes and complexity of disease neuropathology. However, one common feature shared among all these vascular causes is cerebral blood flow (CBF) dysregulation, and chronic cerebral hypoperfusion (CCH) is the universal consequence of CBF dysregulation, which subsequently results in an insufficient blood supply to the brain, ultimately contributing to VCID. The purpose of this comprehensive review is to emphasize the important contributions of CCH to VCID and illustrate the current findings about the mechanisms involved in CCH-induced VCID pathological changes. Specifically, evidence is mainly provided to support the molecular mechanisms, including Aβ accumulation, inflammation, oxidative stress, blood-brain barrier (BBB) disruption, trophic uncoupling and white matter lesions (WMLs). Notably, there are close interactions among these multiple mechanisms, and further research is necessary to elucidate the hitherto unsolved questions regarding these interactions. An enhanced understanding of the pathological features in preclinical models could provide a theoretical basis, ultimately achieving the shift from treatment to prevention.

Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer's disease.

To match the metabolic demands of the brain, mechanisms have evolved to couple neuronal activity to vasodilation, thus increasing local cerebral blood flow and delivery of oxygen and glucose to active neurons. Rather than relying on metabolic feedback signals such as the consumption of oxygen or glucose, the main signalling pathways rely on the release of vasoactive molecules by neurons and astrocytes, which act on contractile cells. Vascular smooth muscle cells and pericytes are the contractile cells associated with arterioles and capillaries, respectively, which relax and induce vasodilation.Much progress has been made in understanding the complex signalling pathways of neurovascular coupling, but issues such as the contributions of capillary pericytes and astrocyte calcium signal remain contentious. Study of neurovascular coupling mechanisms is especially important as cerebral blood flow dysregulation is a prominent feature of Alzheimer’s disease. In this article we will discuss developments and controversies in the understanding of neurovascular coupling and finish by discussing current knowledge concerning neurovascular uncoupling in Alzheimer’s disease.

Emerging Links between Cerebral Blood Flow Regulation and Cognitive Decline: A Role for Brain Microvascular Pericytes.

Cognitive impairment associated with vascular etiology has been of considerable interest in the development of dementia. Recent studies have started to uncover cerebral blood flow deficits in initiating cognitive deterioration. Brain microvascular pericytes, the only type of contractile cells in capillaries, are involved in the precise modulation of vascular hemodynamics due to their ability to regulate resistance in the capillaries. They exhibit potential in maintaining the capillary network geometry and basal vascular tone. In addition, pericytes can facilitate better blood flow supply in response to neurovascular coupling. Their dysfunction is thought to disturb cerebral blood flow causing metabolic imbalances or structural injuries, leading to consequent cognitive decline. In this review, we summarize the characteristics of microvascular pericytes in brain blood flow regulation and outline the framework of a two-hit hypothesis in cognitive decline, where we emphasize how pericytes serve as targets of cerebral blood flow dysregulation that occurs with neurological challenges, ranging from genetic factors, aging, and pathological proteins to ischemic stress.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy.

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain.

Age-related phenotypic changes of cerebromicrovascular endothelial cells lead to dysregulation of cerebral blood flow and blood-brain barrier disruption, promoting the pathogenesis of vascular cognitive impairment (VCI). In recent years, endothelial cell senescence has emerged as a potential mechanism contributing to microvascular pathologies opening the avenue to the therapeutic exploitation of senolytic drugs in preclinical studies. However, difficulties with the detection of senescent endothelial cells in wild type mouse models of aging hinder the assessment of the efficiency of senolytic treatments. To detect senescent endothelial cells in the aging mouse brain, we analyzed 4233 cells in fractions enriched for cerebromicrovascular endothelial cells and other cells associated with the neurovascular unit obtained from young (3-month-old) and aged (28-month-old) C57BL/6 mice. We define 13 transcriptomic cell types by deep, single-cell RNA sequencing. We match transcriptomic signatures of cellular senescence to endothelial cells identified on the basis of their gene expression profile. Our study demonstrates that with advanced aging, there is an increased ratio of senescent endothelial cells (~ 10%) in the mouse cerebral microcirculation. We propose that our single-cell RNA sequencing-based method can be adapted to study the effect of aging on senescence in various brain cell types as well as to evaluate the efficiency of various senolytic regimens in multiple tissues.

Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects.

Aging-induced structural and functional alterations of the neurovascular unit lead to impairment of neurovascular coupling responses, dysregulation of cerebral blood flow, and increased neuroinflammation, all of which contribute importantly to the pathogenesis of age-related vascular cognitive impairment (VCI). There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in age-related neurovascular and cerebromicrovascular dysfunction. Our recent studies demonstrate that restoring cellular NAD+ levels in aged mice rescues neurovascular function, increases cerebral blood flow, and improves performance on cognitive tasks. To determine the effects of restoring cellular NAD+ levels on neurovascular gene expression profiles, 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2weeks. Transcriptome analysis of preparations enriched for cells of the neurovascular unit was performed by RNA-seq. Neurovascular gene expression signatures in NMN-treated aged mice were compared with those in untreated young and aged control mice. We identified 590 genes differentially expressed in the aged neurovascular unit, 204 of which are restored toward youthful expression levels by NMN treatment. The transcriptional footprint of NMN treatment indicates that increased NAD+ levels promote SIRT1 activation in the neurovascular unit, as demonstrated by analysis of upstream regulators of differentially expressed genes as well as analysis of the expression of known SIRT1-dependent genes. Pathway analysis predicts that neurovascular protective effects of NMN are mediated by the induction of genes involved in mitochondrial rejuvenation, anti-inflammatory, and anti-apoptotic pathways. In conclusion, the recently demonstrated protective effects of NMN treatment on neurovascular function can be attributed to multifaceted sirtuin-mediated anti-aging changes in the neurovascular transcriptome. Our present findings taken together with the results of recent studies using mitochondria-targeted interventions suggest that mitochondrial rejuvenation is a critical mechanism to restore neurovascular health and improve cerebral blood flow in aging.

Identifying psychosis spectrum youth using support vector machines and cerebral blood perfusion as measured by arterial spin labeled fMRI

Altered cerebral blood flow (CBF), as measured by arterial spin labelling (ASL), has been observed in several psychiatric conditions, but is a generally underutilized MRI technique, especially in the study of psychosis spectrum (PS) symptoms. We aimed to determine group differences in ASL resting state functional connectivity (rsFC) between PS and non-PS youth, and the reliability of a support vector machine (SVM) classifier trained on ASL rsFC features to differentiate PS and non-PS youth, especially compared to blood oxygen level dependent (BOLD) fMRI. 1146 youth aged 8–22 with ASL and BOLD data from the Philadelphia Neurodevelopmental Cohort were analyzed. Widespread ASL hyperconnectivity was found in the left cuneus, precuneus, and dorsolateral prefrontal cortex, and hypoconnectivity was found in the left cingulate cortex and orbitofrontal area (multiple linear regression, FDR corrected). An SVM trained on ASL and BOLD features outperformed either modality alone (AUCBOTH = 0.72 versus AUCASL = 0.68 and AUCBOLD = 0.67). Classification performance and precision improved when the non-PS group had no psychiatric comorbidities. The relative success of the classifier suggests ASL rsFC changes exist in PS individuals that differ from BOLD rsFC changes, and extends previous findings of CBF dysregulation in PS.

Abstract 357: Cerebral Arterial Endothelial Dysfunction in the Post-Cardiac Arrest Period

Introduction: Cardiac arrest (CA) has a poor prognosis due to brain injury that progresses over time. Endothelial dysfunction may play an important role in the impairment of the cerebral circulation after CA. Aims: To investigate 1) whether endothelial dysfunction is present in cerebral arteries, and 2) if the altered endothelial function is caused by increased activity of calcium-activated potassium (K ca ) channels. Methods: Male Sprague-Dawley rats (403g±24g) were anaesthetized, intubated and ventilated. Four groups were examined; two CA groups observed for either 2 hours (2h-CA, n=10) or 4 hours (4h-CA, n=10) and two corresponding sham groups (2h-sham, n=10; 4h-sham, n=10). Following 7 minutes of asphyxial CA, the rats were resuscitated using adrenaline, ventilation, and chest compressions. Middle cerebral arteries were isolated and examined in wire-myographs. Results: Cerebral vasodilation was significantly enhanced in response to bradykinin in arteries from 4h-CA rats when compared to 4h-sham rats (4h-sham: E max 58% (5.57 of 9.69) ± 6% vs 4h-CA: E max 84% (6.16 of 7.32) ± 4%, p=0.007). Likewise, vasodilation induced by NS309 (K Ca -channel activator) was increased in CA rats when compared to sham rats. In the presence of L-NAME (NO synthase inhibitor), bradykinin induced vasodilation was significantly augmented in 4h-CA rats when compared to 4h-sham rats, whereas SNP (NO donor) induced vasodilation was similar between groups. In the presence of L-NAME and K Ca -channel blockers (UCL1684 and ICA-17043), bradykinin induced vasodilation was abolished in cerebral arteries in all four groups. Conclusion: Our findings demonstrate an enhanced endothelial-dependent vasodilation in cerebral arteries in the post-cardiac arrest period. The increased vasodilatory response may be explained by increased endothelial K Ca -channel activity and bioavailability of NO, and may contribute to dysregulation of cerebral blood flow after CA.

Hypertension Exacerbates Cerebrovascular Oxidative Stress Induced by Mild Traumatic Brain Injury: Protective Effects of the Mitochondria-Targeted Antioxidative Peptide SS-31.

Traumatic brain injury (TBI) induces cerebrovascular oxidative stress, which is associated with neurovascular uncoupling, autoregulatory dysfunction, and persisting cognitive decline in both pre-clinical models and patients. However, single mild TBI (mTBI), the most frequent form of brain trauma, increases cerebral generation of reactive oxygen species (ROS) only transiently. We hypothesized that comorbid conditions might exacerbate long-term ROS generation in cerebral arteries after mTBI. Because hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive and spontaneously hypertensive rats (SHR) and assessed changes in cytoplasmic and mitochondrial superoxide (O2-) production by confocal microscopy in isolated middle cerebral arteries (MCA) 2 weeks after mTBI using dihydroethidine (DHE) and the mitochondria-targeted redox-sensitive fluorescent indicator dye MitoSox. We found that mTBI induced a significant increase in long-term cytoplasmic and mitochondrial O2- production in MCAs of SHRs and increased expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit Nox4, which were reversed to the normal level by treating the animals with the cell-permeable, mitochondria-targeted antioxidant peptide SS-31 (5.7 mg kg-1 day-1, i.p.). Persistent mTBI-induced oxidative stress in MCAs of SHRs was significantly decreased by inhibiting vascular NADPH oxidase (apocyinin). We propose that hypertension- and mTBI-induced cerebrovascular oxidative stress likely lead to persistent dysregulation of cerebral blood flow (CBF) and cognitive dysfunction, which might be reversed by SS-31 treatment.

Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment.

There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer’s disease (AD), characterized by progressive cognitive impairment, memory loss, and thinking or speech problems. VaD is usually caused by cerebrovascular disease, during which, cerebrovascular endothelial cells (CECs) are vulnerable. CEC dysfunction occurs before the onset of VaD and can eventually lead to dysregulation of cerebral blood flow and blood–brain barrier damage, followed by the activation of glia and inflammatory environment in the brain. White matter, neuronal axons, and synapses are compromised in this process, leading to cognitive impairment. The present review summarizes the mechanisms underlying CEC impairment during hypoperfusion and pathological role of CECs in VaD. Through the comprehensive examination and summarization, endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway, Ras homolog gene family member A (RhoA) signaling pathway, and CEC-derived caveolin-1 (CAV-1) are proposed to serve as targets of new drugs for the treatment of VaD.

Dynamic autoregulation of cerebral blood flow measured non-invasively with fast diffuse correlation spectroscopy

Cerebral autoregulation (CA) maintains cerebral blood flow (CBF) in the presence of systemic blood pressure changes. Brain injury can cause loss of CA and resulting dysregulation of CBF, and the degree of CA impairment is a functional indicator of cerebral tissue health. Here, we demonstrate a new approach to noninvasively estimate cerebral autoregulation in healthy adult volunteers. The approach employs pulsatile CBF measurements obtained using high-speed diffuse correlation spectroscopy (DCS). Rapid thigh-cuff deflation initiates a chain of responses that permits estimation of rates of dynamic autoregulation in the cerebral microvasculature. The regulation rate estimated with DCS in the microvasculature (median: 0.26 s−1, inter quartile range: 0.19 s−1) agrees well (R = 0.81, slope = 0.9) with regulation rates measured by transcranial Doppler ultrasound (TCD) in the proximal vasculature (median: 0.28 s−1, inter quartile range: 0.10 s−1). We also obtained an index of systemic autoregulation in concurrently measured scalp microvasculature. Systemic autoregulation begins later than cerebral autoregulation and exhibited a different rate (0.55 s−1, inter quartile range: 0.72 s−1). Our work demonstrates the potential of diffuse correlation spectroscopy for bedside monitoring of cerebral autoregulation in the microvasculature of patients with brain injury.

NIRS-based cerebrovascular regulation assessment: exercise and cerebrovascular reactivity.

Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions. Near-infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation ([Formula: see text]) provides an estimate of oxygenation of interrogated cerebral volume useful in identifying variations in oxygen supply to cerebral tissue and in monitoring cerebrovascular function. [Formula: see text]-inhalation-based hypercapnic breathing challenges were used to simulate CBF dysregulation, utilizing NIRS to monitor the CBF autoregulatory response. A breathing circuit was designed to administer [Formula: see text]-compressed air mixtures and assess CBF regulatory responses to hypercapnia in 26 healthy young adults. One to three hypercapnic challenges of 5 or 10min duration were delivered to each subject while continuously monitoring [Formula: see text], partial pressure of end tidal [Formula: see text] ([Formula: see text]), and vital signs. Change in [Formula: see text] ([Formula: see text]) during [Formula: see text] inhalation positively correlated to [Formula: see text] ([Formula: see text]). Grouping subjects into three exercise factor levels (h/week), (1)0, (2)[Formula: see text] and [Formula: see text], and (3)[Formula: see text] showed significantly greater [Formula: see text] responses to [Formula: see text] challenges for level 3 subjects but similar [Formula: see text] responses for the three groups. Exercising greater than 10h/week may produce a higher resting cerebrovascular reactivity (CVR) to [Formula: see text] inhalation. Establishing baseline values of [Formula: see text] and CVR to [Formula: see text] may aid in early detection of CBF changes.

Cerebral perfusion alterations in type 2 diabetes and its relation to insulin resistance and cognitive dysfunction

To explore the effect of T2DM on cerebral perfusion, and the relationship between cerebral perfusion changes and cognitive impairment as well as diabetic variables, by using a whole-brain arterial spin-labeling (ASL) MRI technique. This prospective study was approved by the local institutional review board and was performed between November 2012 and October 2013. All subjects provided informed consent. Forty T2DM patients and 41 age-, sex- and education-matched healthy controls were included. Cerebral blood flow (CBF) map was obtained by pulsed ASL perfusion imaging at 3 T MRI. Voxel-wise comparisons on CBF maps with and without partial volume effects (PVEs) correction were performed between groups. Associations between CBF and cognitive functioning, and between CBF and diabetic variables were investigated by using voxel-wise, whole-brain correlation analyses. In T2DM patients, PVEs uncorrected CBF was decreased in the posterior cingulate cortex (PCC), precuneus and bilateral occipital lobe, and increased in the anterior cingulate cortex (corrected P < .05). These changes were largely unchanged after PVEs correction. Correlation analyses revealed that in patients, hypoperfusion in PCC and precuneus regions were related to higher insulin resistance level and deficits in clock-drawing performance, while the occipital hypoperfusion was associated with worse visual-memory performance, regardless of PVEs correction. The cerebral hypoperfusion pattern in T2DM resembles the pattern observed in the early stage of dementia, and increased insulin resistance might be an important risk factor as well as treatment target for such CBF dysregulation.

Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling: Pathomechanisms, perspectives, and therapeutic implications.

Traumatic brain injury (TBI) is a major health problem worldwide. In addition to its high mortality (35-40%), survivors are left with cognitive, behavioral, and communicative disabilities. While little can be done to reverse initial primary brain damage caused by trauma, the secondary injury of cerebral tissue due to cerebromicrovascular alterations and dysregulation of cerebral blood flow (CBF) is potentially preventable. This review focuses on functional, cellular, and molecular changes of autoregulatory function of CBF (with special focus on cerebrovascular myogenic response) that occur in cerebral circulation after TBI and explores the links between autoregulatory dysfunction, impaired myogenic response, microvascular impairment, and the development of secondary brain damage. We further provide a synthesized translational view of molecular and cellular mechanisms involved in cortical spreading depolarization-related neurovascular dysfunction, which could be targeted for the prevention or amelioration of TBI-induced secondary brain damage.