scholarly journals Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Cina Sasannejad ◽  
E. Wesley Ely ◽  
Shouri Lahiri
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Distress Syndrome ◽  
Brain Barrier ◽  
Pathophysiological Mechanisms ◽  
Blood Brain

Abstract Acute respiratory distress syndrome (ARDS) survivors experience a high prevalence of cognitive impairment with concomitantly impaired functional status and quality of life, often persisting months after hospital discharge. In this review, we explore the pathophysiological mechanisms underlying cognitive impairment following ARDS, the interrelations between mechanisms and risk factors, and interventions that may mitigate the risk of cognitive impairment. Risk factors for cognitive decline following ARDS include pre-existing cognitive impairment, neurological injury, delirium, mechanical ventilation, prolonged exposure to sedating medications, sepsis, systemic inflammation, and environmental factors in the intensive care unit, which can co-occur synergistically in various combinations. Detection and characterization of pre-existing cognitive impairment imparts challenges in clinical management and longitudinal outcome study enrollment. Patients with brain injury who experience ARDS constitute a distinct population with a particular combination of risk factors and pathophysiological mechanisms: considerations raised by brain injury include neurogenic pulmonary edema, differences in sympathetic activation and cholinergic transmission, effects of positive end-expiratory pressure on cerebral microcirculation and intracranial pressure, and sensitivity to vasopressor use and volume status. The blood-brain barrier represents a physiological interface at which multiple mechanisms of cognitive impairment interact, as acute blood-brain barrier weakening from mechanical ventilation and systemic inflammation can compound existing chronic blood-brain barrier dysfunction from Alzheimer’s-type pathophysiology, rendering the brain vulnerable to both amyloid-beta accumulation and cytokine-mediated hippocampal damage. Although some contributory elements, such as the presenting brain injury or pre-existing cognitive impairment, may be irreversible, interventions such as minimizing mechanical ventilation tidal volume, minimizing duration of exposure to sedating medications, maintaining hemodynamic stability, optimizing fluid balance, and implementing bundles to enhance patient care help dramatically to reduce duration of delirium and may help prevent acquisition of long-term cognitive impairment.

scholarly journals Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment

2019 ◽  
Vol 11 ◽  
pp. 117957351984065 ◽  
Author(s):  
Divine C Nwafor ◽  
Allison L Brichacek ◽  
Afroz S Mohammad ◽  
Jessica Griffith ◽  
Brandon P Lucke-Wold ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
The United States ◽  
Brain Barrier ◽  
Blood Brain ◽  
Systemic Inflammatory Disease ◽  
Sepsis Survivors ◽  
The Brain

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB’s role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

scholarly journals Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bailey Hiles-Murison ◽  
Andrew P. Lavender ◽  
Mark J. Hackett ◽  
Joshua J. Armstrong ◽  
Michael Nesbit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Hippocampal Formation ◽  
Brain Barrier ◽  
Lateral Ventricles ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Underlying Mechanisms

AbstractRepeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits.

Removal of a compressive mass causes a transient disruption of blood-brain barrier but a long-term recovery of spiny stellate neurons in the rat somatosensory cortex

2021 ◽  
pp. 1-17
Author(s):  
Tzu-Yin Yeh ◽  
Pei-Hsin Liu
Keyword(s):  
Somatosensory Cortex ◽  
Blood Brain Barrier ◽  
Dendritic Spines ◽  
Late Onset ◽  
Brain Barrier ◽  
Blood Brain ◽  
Afferent Fibers ◽  
Prolonged Recovery ◽  
Rat Somatosensory Cortex

Background: In the cranial cavity, a space-occupying mass such as epidural hematoma usually leads to compression of brain. Removal of a large compressive mass under the cranial vault is critical to the patients. Objective: The purpose of this study was to examine whether and to what extent epidural decompression of the rat primary somatosensory cortex affects the underlying microvessels, spiny stellate neurons and their afferent fibers. Methods: Rats received epidural decompression with preceding 1-week compression by implantation of a bead. The thickness of cortex was measured using brain coronal sections. The permeability of blood-brain barrier (BBB) was assessed by Evans Blue and immunoglobulin G extravasation. The dendrites and dendritic spines of the spiny stellate neurons were revealed by Golgi— Cox staining and analyzed. In addition, the thalamocortical afferent (TCA) fibers in the cortex were illustrated using anterograde tracing and examined. Results: The cortex gradually regained its thickness over time and became comparable to the sham group at 3 days after decompression. Although the diameter of cortical microvessels were unaltered, a transient disruption of the BBB was observed at 6 hours and 1 day after decompression. Nevertheless, no brain edema was detected. In contrast, the dendrites and dendritic spines of the spiny stellate neurons and the TCA fibers were markedly restored from 2 weeks to 3 months after decompression. Conclusions: Epidural decompression caused a breakdown of the BBB, which was early-occurring and short-lasting. In contrast, epidural decompression facilitated a late-onset and prolonged recovery of the spiny stellate neurons and their afferent fibers.

scholarly journals ELEVATION OF MATRIX METALLOPROTEINASES 3 AND 9 IN CEREBROSPINAL FLUID AND BLOOD IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

Neurosurgery ◽  
2009 ◽  
Vol 65 (4) ◽  
pp. 702-708 ◽  
Author(s):  
Mark Grossetete ◽  
Jeremy Phelps ◽  
Leopold Arko ◽  
Howard Yonas ◽  
Gary A. Rosenberg
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Matrix Metalloproteinases ◽  
Blood Brain Barrier ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Brain Barrier ◽  
Western Immunoblot ◽  
Blood Brain

Abstract OBJECTIVE Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.

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