Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic–ischaemic brain injury after cardiac arrest DOI Creative Commons
Ryan L. Hoiland, Chiara Robba,

David K. Menon

et al.

Intensive Care Medicine, Journal Year: 2023, Volume and Issue: 49(9), P. 1062 - 1078

Published: July 28, 2023

The cerebral oxygen cascade includes three key stages: (a) convective delivery representing the bulk flow of to vascular bed; (b) diffusion from blood into brain tissue; and (c) cellular utilisation for aerobic metabolism. All stages may become dysfunctional after resuscitation cardiac arrest contribute hypoxic–ischaemic injury (HIBI). Improving by optimising has been widely investigated as a strategy mitigate HIBI. However, clinical trials aimed at have yielded neutral results. Advances in understanding HIBI pathophysiology suggest that impairments pertaining should also be considered identifying therapeutic strategies management patients. Culprit mechanisms these include widening barrier due peri-vascular oedema mitochondrial dysfunction. An integrated approach encompassing both intra-parenchymal non-invasive neuromonitoring techniques aid detecting pathophysiologic changes enable patient-specific reducing severity

Language: Английский

Revisiting the neurovascular unit DOI

Samantha Schaeffer,

Costantino Iadecola

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(9), P. 1198 - 1209

Published: Aug. 5, 2021

Language: Английский

Citations

430
Biological aging processes underlying cognitive decline and neurodegenerative disease DOI Creative Commons
Mitzi M. Gonzales, Valentina R. Garbarino, Erin Pollet

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(10)

Published: May 15, 2022

Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability mortality in later life. As with many chronic conditions, aging is single most influential factor development of ADRD. Even older adults who remain free dementia throughout their lives, cognitive decline neurodegenerative changes appreciable advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview cognition, brain morphology, neuropathological protein accumulation across lifespan humans, complementary mechanistic evidence from animal models. Next, highlight selected processes that differentially regulated disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular inflammation, lipid dysregulation. We summarize research clinical translational studies link biological underlying ADRD pathogenesis. Targeting fundamental may represent a yet relatively unexplored avenue attenuate both age-related Collaboration fields geroscience neuroscience, coupled new models more closely align human processes, necessary advance novel therapeutic discovery realm.

Language: Английский

Citations

181
Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial DOI Creative Commons
Jeanette Tas, Erta Beqiri,

Ruud CR van Kaam

et al.

Journal of Neurotrauma, Journal Year: 2021, Volume and Issue: 38(20), P. 2790 - 2800

Published: Aug. 18, 2021

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated improved outcome and might be useful individualize care, but has never been prospectively evaluated. This study evaluated feasibility safety of CA-guided management in TBI requiring intracranial monitoring therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment Target Effectiveness (COGiTATE) parallel two-arm trial took place four tertiary centers. TBIicp were randomized either Brain Trauma Foundation (BTF) guideline target range (control group) or individualized targets (intervention group). guided by six times daily software-based alerts for up 5 days. primary end-point was percentage time concordant (±5 mm Hg) set targets. main secondary an increase therapeutic intensity level (TIL) between control intervention group. Twenty-eight 32 group 46.5% (interquartile range, 41.2-58) monitored time, significantly higher than specified published protocol (36%;

Language: Английский

Citations

150
Hypertension, Neurovascular Dysfunction, and Cognitive Impairment DOI Open Access
Monica M. Santisteban, Costantino Iadecola, Daniela Carnevale

et al.

Hypertension, Journal Year: 2022, Volume and Issue: 80(1), P. 22 - 34

Published: Oct. 5, 2022

Hypertension affects a significant proportion of the adult and aging population represents an important risk factor for vascular cognitive impairment late-life dementia. Chronic high blood pressure continuously challenges structural functional integrity cerebral vasculature, leading to microvascular rarefaction dysfunction, neurovascular uncoupling that typically impairs supply. disrupts blood-brain barrier integrity, promotes neuroinflammation, may contribute amyloid deposition Alzheimer pathology. The mechanisms underlying these harmful effects are still focus investigation, but studies in animal models have provided molecular cellular mechanistic insights. Remaining questions relate whether adequate treatment hypertension prevent deterioration function, threshold treatment, most effective antihypertensive drugs. Recent advances biology, advanced brain imaging, detection subtle behavioral phenotypes begun provide insights into critical issues. Importantly, parallel analysis parameters humans is feasible, making it possible foster translational advancements. In this review, we evaluation evidence available experimental examine progress made identify remaining gaps knowledge.

Language: Английский

Citations

128
Losing the dogmatic view of cerebral autoregulation DOI
Patrice Brassard, Lawrence Labrecque, Jonathan D. Smirl

et al.

Physiological Reports, Journal Year: 2021, Volume and Issue: 9(15)

Published: July 28, 2021

In 1959, Niels Lassen illustrated the cerebral autoregulation curve in classic review article entitled Cerebral Blood Flow and Oxygen Consumption Man. This concept suggested a relatively broad mean arterial pressure range (~60–150 mmHg) wherein blood flow remains constant. However, assumption that this wide plateau could be applied on within-individual basis is incorrect greatly variable between individuals. Indeed, each data point autoregulatory originated from independent samples of participants patients represented interindividual relationships pressure. Nonetheless, influential commonly cited various high-impact publications medical textbooks, frequently taught science education without appropriate nuances caveats. Herein, we provide rationale additional experimental supporting notion need to lose dogmatic view autoregulation.

Language: Английский

Citations

116
New Insights Into Cerebrovascular Pathophysiology and Hypertension DOI Creative Commons
Alastair J.S. Webb, David J. Werring

Stroke, Journal Year: 2022, Volume and Issue: 53(4), P. 1054 - 1064

Published: March 8, 2022

Despite advances in acute management and prevention of cerebrovascular disease, stroke vascular cognitive impairment together remain the world's leading cause death neurological disability. Hypertension its consequences are associated with over 50% ischemic 70% hemorrhagic strokes but despite good control blood pressure (BP), there remains a 10% risk recurrent events, is no proven strategy to prevent impairment. evolves lifespan, from predominant sympathetically driven hypertension elevated mean BP early mid-life late-life phenotype increasing systolic falling diastolic pressures, increased arterial stiffness aortic pulsatility. This pattern may partially explain both incidence younger adults as well late-onset, chronic injury concurrent historic hypertension. With autonomic dysfunction, variability increases, independently predicting intracerebral hemorrhage, potentially modifiable beyond BP. However, interaction between cerebral flow poorly understood. Cerebral small vessel disease pulsatility large vessels reduced reactivity carbon dioxide, which being targeted phase clinical trials. mainly dependent upon transmission via stiff brain, while reflects endothelial dysfunction. In contrast, although autoregulation critical adapt tone fluctuations maintain flow, role factor for uncertain. New insights into hypertension-associated pathophysiology provide key targets

Language: Английский

Citations

91
Transfer function analysis of dynamic cerebral autoregulation: A CARNet white paper 2022 update DOI Creative Commons
Ronney B. Panerai, Patrice Brassard, Joel S. Burma

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2022, Volume and Issue: 43(1), P. 3 - 25

Published: Aug. 12, 2022

Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response changes perfusion pressure. Due challenges measuring intracranial pressure, CA is often described as relationship between mean arterial pressure (MAP) and CBF. Dynamic (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being most common. A 2016 white paper by members an international Cerebrovascular Research Network (CARNet) that focused on strove improve TFA standardization way introducing data acquisition, analysis, reporting guidelines. Since then, additional evidence has allowed for improvement refinement original recommendations, well inclusion new guidelines reflect recent advances field. This second edition contains more robust, evidence-based which have been expanded address current streams inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating dCA metrics, incorporating quantification into clinical trials. Implementation these revised recommendations important reliability reproducibility studies, facilitate inter-institutional collaboration comparison results studies.

Language: Английский

Citations

83
The Neurovasculome: Key Roles in Brain Health and Cognitive Impairment: A Scientific Statement From the American Heart Association/American Stroke Association DOI Open Access
Costantino Iadecola, Eric E. Smith, Josef Anrather

et al.

Stroke, Journal Year: 2023, Volume and Issue: 54(6)

Published: April 3, 2023

Preservation of brain health has emerged as a leading public priority for the aging world population. Advances in neurovascular biology have revealed an intricate relationship among cells, meninges, and hematic lymphatic vasculature (the neurovasculome) that is highly relevant to maintenance cognitive function. In this scientific statement, multidisciplinary team experts examines these advances, assesses their relevance disease, identifies knowledge gaps, provides future directions.

Language: Английский

Citations

79
Vascular contributions to Alzheimer's disease DOI Creative Commons
Laura Eisenmenger,

Anthony Peret,

Bolanle M. Famakin

et al.

Translational research, Journal Year: 2022, Volume and Issue: 254, P. 41 - 53

Published: Dec. 15, 2022

Language: Английский

Citations

74
Posterior Reversible Encephalopathy Syndrome DOI
Romergryko G. Geocadin

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(23), P. 2171 - 2178

Published: June 7, 2023

Headache, visual disturbances, encephalopathy, and seizures may be due to acute, severe hypertension or toxic agents, especially chemotherapy. Imaging shows cerebral edema in posterior parts of the brain.

Language: Английский

Citations

47