Reduction In Cerebral Perfusion Research Articles

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage.

Nimodipine is routinely administered to aneurysmal subarachnoid hemorrhage patients to improve functional outcomes. Nimodipine can induce marked systemic hypotension, which might impair cerebral perfusion and brain metabolism. Twenty-seven aneurysmal subarachnoid hemorrhage patients having multimodality neuromonitoring and oral nimodipine treatment as standard of care were included in this retrospective study. Alterations in mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), brain tissue oxygen tension (pbtO2), and brain metabolism (cerebral microdialysis), were investigated up to 120 minutes after oral administration of nimodipine (60mg or 30mg), using mixed linear models. Three thousand four hundred twenty-five oral nimodipine administrations were investigated (126±59 administrations/patient). After 60mg of oral nimodipine, there was an immediate statistically significant (but clinically irrelevant) drop in MAP (relative change, 0.97; P<0.001) and CPP (relative change: 0.97; P<0.001) compared with baseline, which lasted for the whole 120 minutes observation period (P<0.001). Subsequently, pbtO2 significantly decreased 50 minutes after administration (P=0.04) for the rest of the observation period; the maximum decrease was -0.6mmHg after 100 minutes (P<0.001). None of the investigated cerebral metabolites (glucose, lactate, pyruvate, lactate/pyruvate ratio, glutamate, glycerol) changed after 60mg nimodipine. Compared with 60mg nimodipine, 30mg induced a lower reduction in MAP (relative change, 1.01; P=0.02) and CPP (relative change, 1.01; P=0.03) but had similar effects on pbtO2 and cerebral metabolism (P>0.05). Oral nimodipine reduced MAP, which translated into a reduction in cerebral perfusion and oxygenation. However, these changes are unlikely to be clinically relevant, as the absolute changes were minimal and did not impact cerebral metabolism.

EEG response to a high volume (1.5 mL/kg) caudal block in infants less than 3 months

IntroductionThe substantial compression of the dural sac and the subsequent cranial shift of cerebrospinal fluid caused by a high-volume caudal block has been shown to significantly but transiently reduce cerebral...

PRELIMINARY ANALYSIS OF BRAIN PERFUSION OBTAINED WITH ARTERIAL SPIN LABELING METHOD (ASL) USED TO EVALUATE THE EFFECTS OF TYPE 2 DIABETES IN MORBIDLY OBESE PATIENTS

Introduction: Earlier studies demonstrated that obesity was associated with lower cerebral perfusion in obese participants, as compared to participants at normal weight, especially in frontal grey matter regions. On the other hand, type 2 diabetes is a common co-morbid condition among obese patients, and it is associated per se with brain structural and metabolic abnormalities that are related to lower cerebral blood flow (CBF). Unfortunately, only two studies evaluated the effects on co-morbid T2D on CBF, one of them in adolescent population. Therefore, the aim of this study was to establish a pipeline process to quantify CBF images that were obtained in an independent project evaluating brain abnormalities associated with morbid obesity and their resolution with intragastric balloon – an invasive method to reduce weight. Furthermore, we compared CBF between obese patients with and without type 2 diabetes, as well as controls at normal weight. Methods: A processing pipeline utilizing SPM12 toolbox and digital maps (AAL, Brodmann) was established to automatically pre-process scans and toolbox REX was used to prepare data for statistical analysis. We used it to analyze data for six morbidly obese patients with type 2 diabetes T2D (O-T2D) (average age = 48.5 ± 7.9, average body weight = 125.0 ± 29.8 kg, average BMI = 42.0 ± 9.4), eight morbidly obese patients without T2D (O-NT2D) (average age = 39.1 ± 16.1, average body weight = 138.2 ± 14.9 kg, average BMI = 50.2 ± 6.5) and eight healthy controls with normal weight (CON) (average age = 43.5 ± 11.5, average body weight = 67.4 ± 14.6 kg, average BMI = 23.4 ± 3.5). All studies were performed at the CNS Lab MRI Centre, NIBBE. Results: These preliminary analyses demonstrated lower cerebral blood flow in frontal cortex in obese patients with T2D, as compared to obese patients without T2D and controls. Conclusion: A pipeline to numerically process ASL-CBF data was created and used to analyse the small dataset. The analyses indicated that not morbid obesity per se, but morbid obesity combined with co-morbid type 2 diabetes is associated with widespread reductions in cerebral perfusion. The results are in line with other studies that were limited to subjects with lower stages of overweight and obesity. We believe that this methodology may be applied to study changes in brain perfusion evoked by simulated hypergravity with Lower Body Negative Pressure (LBNP) device placed within a magnetic resonance scanner or perfusion changes induced by hypoxia.

Cerebral perfusion and its association with serum endothelin-1 in multiple sclerosis

ABSTRACT Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and degenerative disease of the central nervous system. The exact pathogenesis of MS is incompletely understood. Cerebral vascular pathology is frequently verified in this disease. Perfusion studies may put light on the disease pathogenesis. In this study, we use dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (DSC-MRI) to evaluate the cerebral perfusion in a group of MS patients. Thirty patients with relapsing–remitting multiple sclerosis (RRMS) and 20 healthy controls were investigated. The perfusion parameters were assessed for normal-appearing white matter (NAWM) and deep gray matter (DGM). Also, the serum level of the potent vasoconstrictor, endothelin-1(ET-1), was evaluated. There was reduction in cerebral perfusion in MS patients in comparison to healthy controls in the NAWM and (DGM). In addition, serum (ET-1) level was significantly elevated in the patient group and was correlated with the perfusion parameters. These findings suggest that cerebral hypoperfusion may play an important role in the pathogenesis of MS lesions. ET-1 has a role in cerebral hypoperfusion in both NAWM and DGM of RRMS patients. DSC-MRI could be an applicable objective measure to detect cerebral hemodynamic changes in MS.

The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a dominant cause of death and disability worldwide. A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neurons, which subsequently promotes a series of pathophysiological responses leading to neuronal death. Many previous experimental studies have reported that excitotoxicity, mitochondrial death pathways, the release of free radicals, protein misfolding, apoptosis, necrosis, autophagy, and inflammation are involved solely or in combination in this disorder. Among them, irreversible neuronal apoptosis plays a key role in both short- and long-term prognoses after SAH. Neuronal apoptosis occurs through multiple pathways including extrinsic, mitochondrial, endoplasmic reticulum, p53 and oxidative stress. Meanwhile, a large number of blood contents enter the subarachnoid space after SAH, and the secondary metabolites, including oxygenated hemoglobin and heme, further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema, causing early brain injury and delayed cerebral ischemia, and ultimately increasing neuronal apoptosis. Even there is no clear and effective therapeutic strategy for SAH thus far, but by understanding apoptosis, we might excavate new ideas and approaches, as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH. In this review, we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH, which provides a possible target or new strategy for the treatment of SAH.

Characterizing the Dose Response of Hyperoxia with Brain Perfusion.

BACKGROUND: Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries. Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF). Characterizing the relationship between FIO₂ and CBF is necessary to establish FIO₂ levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors. To achieve that goal, this study's objective was to determine whether a dose-response relationship exists between FIO₂ and CBF and, if so, the FIO₂ at which CBF significantly declines.METHODS: Healthy male and female subjects (N = 26) were randomized to receive either low dose FIO₂ of 30%, 40%, 50%, and 100% (Arm 1) or high dose FIO₂ of 60%, 70%, 80%, and 100% (Arm 2), followed by a return to 21% for both groups. Subjects were placed within a 3-Tesla MRI scanner equipped with pseudocontinuous arterial spin labeling software (pCASL) to measure CBF. Baseline CBF measurements were obtained during exposure to 21% FIO₂, with subsequent CBF measurements obtained at each predetermined FIO₂ level.RESULTS: Baseline CBF did not differ between subjects in Arm 1 and Arm 2. Low dose FIO₂ ≤ 50% did not affect CBF. In contrast, high dose FIO₂ ≥ 60% significantly reduced CBF. Exposure to 100% FIO₂ led to similar reductions of CBF for subjects in both Arm 1 and Arm 2.DISCUSSION: The neurovascular system appears to respond to increasing FIO₂ levels in a dose dependent manner, with significant reductions in CBF with FIO₂ exposures ≥ 60%.Damato EG, Fillioe SJ, Vannix IS, Norton LK, Margevicius SP, Beebe JL, Decker MJ. Characterizing the dose response of hyperoxia with brain perfusion. Aerosp Med Hum Perform. 2022; 93(6):493-498.

Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment.

Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI.

Traumatic brain injury of childhood

Traumatic brain injury of childhood

Reactive oxygen species play a modulatory role in the hyperventilatory response to poikilocapnic hyperoxia in humans

The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2 -[H+ ] washout-induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia-induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2 -[H+ ] washout. The hypothetical mechanism for the increase in ventilation ( ) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2 -[H+ ] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX-evoked increase in , 10 healthy men (24±4 years) underwent 10min trials of HX under saline and ascorbic acid infusion. , arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2 ) and CO2 (PCO2 ), pH, oxidant (8-isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8-isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8-isoprostane and attenuated both the reduction in CBF and the HX-induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans-cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2 , which, in turn, seems to be evoked by the excessive ROS production/accumulation.

The enigma of cerebral blood flow and cognition.

The enigma of cerebral blood flow and cognition.

Decreased resting perfusion in precuneus and posterior cingulate cortex predicts tinnitus severity.

Functional magnetic resonance imaging has been increasingly used to understand the mechanisms involved in subjective tinnitus; however, researchers have struggled to reach a consensus about a primary mechanistic model to explain tinnitus. While many studies have used functional connectivity of the BOLD signal to understand how patterns of activity change with tinnitus severity, there is much less research on whether there are differences in more fundamental physiology, including cerebral blood flow, which may help inform the BOLD measures. Here, arterial spin labeling was used to measure perfusion in four regions-of-interest, guided by current models of tinnitus, in a sample of 60 tinnitus patients and 31 control subjects. We found global reductions in cerebral perfusion in tinnitus compared with controls. Additionally, we observed a significant negative correlation between tinnitus severity and perfusion. These results demonstrate that examining perfusion from the whole brain may present a complementary tool for studying tinnitus. More research will help better understand the physiology underlying these differences in perfusion.

Lower body negative pressure protects brain perfusion in aviation gravitational stress induced by push-pull manoeuvre.

Rapid alterations of gravitational stress during high-performance aircraft push-pull manoeuvres induce dramatic shifts in volume and pressure within the circulation system, which may result in loss of consciousness due to the rapid and significant reduction in cerebral perfusion. There are still no specific and effective countermeasures so far. We found that lower body negative pressure (LBNP), applied prior to and during -Gz and released at the subsequent transition to +Gz, could effectively counteract gravitational haemodynamic stress induced by a simulated push-pull manoeuvre and improve cerebral diastolic perfusion in human subjects. We developed a LBNP strategy that effectively protects cerebral perfusion at rapid -Gz to +Gz transitions via improving cerebral blood flow and blood pressure during push-pull manoeuvres and highlight the importance of the timing of the intervention. Our findings provide a systemic link of integrated responses between the peripheral and cerebral haemodynamic changes during push-pull manoeuvres. The acute negative (-Gz) to positive (+Gz) gravity stress during high-performance aircraft push-pull manoeuvres dramatically reduces transient cerebral perfusion, which may lead to loss of vision or even consciousness. The aim of this study was to explore a specific and effective counteractive strategy. Twenty-three healthy young male volunteers (age 21±1year) were subjected to tilting-simulated push-pull manoeuvres. Lower body negative pressure (LBNP) of -40mmHg was applied prior to and during -Gz stress (-0.50 or -0.87Gz) and released at the subsequent transition to +1.00Gz stress. Beat-to-beat cerebral and systemic haemodynamics were continuously recorded during the simulated push-pull manoeuvre in LBNP bouts and corresponding control bouts. During the rapid gravitational transition from -Gz to +Gz, the mean cerebral blood flow velocity decreased significantly in control bouts, while it increased in LBNP bouts (control vs. LBNP bouts, -6.6±4.6 vs. 5.1±6.8cms-1 for -0.50Gz, and -7.4±4.8 vs. 3.4±4.6cms-1 for -0.87 Gz, P<0.01), which was attributed mainly to the elevation of diastolic flow. The LBNP bouts showed much smaller reduction of mean arterial blood pressure at the brain level than control bouts (control bouts vs. LBNP bouts, -38±12 vs. -23±10mmHg for -0.50 to +1.00Gz, and -62±16 vs. -43±11mmHg for -0.87 to +1.00Gz, P<0.01). LBNP applied at -Gz and released at subsequent +Gz had biphasic counteractive effects against the gravitational responses to the push-pull manoeuvre. These data demonstrate that this LBNP strategy could effectively protect cerebral perfusion with dominant improvement of diastolic flow during push-pull manoeuvres.

Targeting cerebrovascular sphingosine‐1‐phosphate signaling to treat heart failure‐induced brain dysfunction

Chronic cardiovascular diseases increasingly emerge as risk factors for neurodegeneration. Heart failure for instance, induces a chronic reduction in cerebral perfusion. Such chronic brain perfusion deficits are frequently accompanied by cognitive decline, which not only seriously impacts the patients’ quality of life but also reduces treatment compliance. Statistically, cognitive impairment is 5 times more prevalent in heart failure patients relative to the age‐matched general population. We previously demonstrated that heart failure associates to augmented signaling of a potent bioactive phospholipid called sphingosine‐1‐phosphate (S1P). During heart failure, such enhanced S1P signaling roots from dysfunctional cystic fibrosis transmembrane regulator (CFTR) expression and activity. CFTR controls the bioavailability of cerebrovascular S1P and hence, its pro‐constrictive effects. In heart failure, reduced microvascular CFTR expression correlates with enhanced myogenic tone and reduced cerebral blood flow.In this study, we investigated the therapeutic potential of CFTR corrector compounds to normalize cerebrovascular S1P signaling and thereby, improve neurological function during experimental heart failure in mice.Systemic CFTR corrector treatment stabilized cerebrovascular CFTR expression, improved myogenic tone and rectified deficient cerebral perfusion in heart failure, without altering the systemic parameters of cardiac output or total peripheral resistance. This normalization associated to recovery of neuronal integrity (i.e., dendrite morphology and dendritic spine density) and cognitive function. The heart failure‐associated dendrite atrophy (i.e., a 22% reduction in dendrite length) was not altered in mice treated with CFTR corrector compound. Longitudinal pre‐treatment (i.e., at 10 weeks post‐infarction) and post‐treatment analyses of the same vehicle‐ and CFTR corrector‐treated HF mice confirmed that CFTR corrector treatment reversed the impaired rhino‐cortical‐dependent, short‐term retention of object familiarity caused by heart failure.Our results put forward a new mechanistic understanding of heart failure‐associated brain complications, and CFTR correctors as potential treatment option for heart failure‐associated cognitive decline.Support or Funding InformationThis work is supported by the Knut &amp; Alice Wallenberg Foundation and the Swedish Research Council.

Effect of Cerebral Blood Flow on Cognition across Healthy Adulthood

Both cognitive function and cerebral blood flow (CBF) decline across the lifespan. However, the relation between them remains unclear, particularly in the context of aging. Furthermore, fitness improves both cognition and CBF, and may be associated with preserved cognitive and cerebrovascular function in an older population.PurposeThe aims of this study were to 1) clarify the effect of CBF on cognition across healthy adulthood, and the extent to which age‐related reductions are modulated by the usually‐observed impairment in cerebrovascular function, and 2) examine the association of aerobic fitness on baseline CBF and cognitive performance in healthy young and older adults.MethodUsing a placebo‐controlled, single‐blinded, randomized cross‐over design, we tested the hypothesis that an acute reduction in CBF (using indomethacin [1.2 mg/kg oral dose]) would impair cognition in both young (n = 13; 25 ± 4y) and older (n = 12; 58 ± 6y) adults. Cerebrovascular function was assessed using blood velocity in the middle cerebral artery (MCAv; Transcranial Doppler Ultrasound). Cerebrovascular CO2 reactivity (CVRCO2) was calculated as the change in MCAv for a given change in end‐tidal CO2 (mm Hg). Cognitive function was measured using visuomotor, inhibitory, and mental switching response time tasks. Aerobic fitness was predicted using a submaximal exercise test (i.e., V̇O2peak). Linear and rank‐based mixed models were used to assess the individual and interactive effects of cerebrovascular function and cognition, while accounting for age, sex, and aerobic fitness.ResultsOlder adults had 11% lower MCAv and 15% worse response time overall (all p ≤ 0.049), but not reliably lower CVRCO2 (p ≥ 0.16). Indomethacin decreased MCAv by 26 ± 11% and CVRCO2 by 69 ± 25% (all p &lt; 0.01), regardless of age. The degree of indomethacin‐induced reductions in CVRCO2 was strongly associated with baseline CVRCO2 (r = 0.87, p &lt; 0.01). Visuomotor response time was 6 ± 13% slower after indomethacin (p = 0.04), but this impairment was not linearly associated with decreases of MCAv (r = −0.26). Finally, aerobic fitness was not associated with baseline CBF in either group (r ≤ 0.14), and was only weakly associated with response time performance in young (r ≤ −0.34), but not older (r ≤ 0.21) adults.ConclusionThe impairments in cognitive function from indomethacin were not evidently associated with the 26% reduction in cerebral perfusion, even in older adults. Compared to young, older adults had worse cognitive performance and decreased CBF but did not have impaired cerebrovascular function. Aerobic fitness was only weakly associated with resting CBF and cognition in both young and older adults. Therefore, cognitive performance may not be influenced by a ≤26% reduction in CBF per se in healthy young and older adults.Support or Funding InformationFunding support from the School of Physical Education, Sport and Exercise Sciences, and Department of Medicine.

Abstract TP319: Risk Factors of Post-stroke Epilepsy

Purpose: The aim of the study was to identify the risk factors for seizures in patients with ischemic stroke using clinical, functional, neuroimaging research methods. Materials and methods: The results of the complex survey of 468 patients suffering from ischemic stroke (256 patients experienced epileptic seizures and 203 experienced no epileptic seizures) are presented. The diagnostic procedures included clinical evaluation, magnetic resonance imaging, electroencephalography, extracranial and transcranial Doppler sonography. In addition the assessment of the rate of sodium lithium countertransport (the marker of genetically determined on transport mechanisms of cell membranes) in patients with c ischemic stroke with the development of epileptic seizures and no seizures was carried out. Results: The focal seizures are the most common (92,5%). Cortical ischemic brain lesions prevailed in patients with seizures (81,1%), whereas in the control group cortex was affected in 38,9% patients (χ2=89.2, &lt;0,001). Stenosis of cerebral arteries was more common in patients with epilepsy (82.3%) compared to patients without seizures (74.4%, &lt;0.05). Reduced cerebrovascular reactivity (CVR) in vertebro-basilar basin was more frequently detected in patients with seizures (85.9%, p&lt;0.001) compared to controls (71.6%). CVR &lt; 10% was registered in 33.8% patients with seizures versus 13.4% controls (p&lt;0.001). Patients with epileptic seizures showed cerebral perfusion reduction mostly in vertebro-basilar basin (85.9%) rather than in carotid basin (61.2%, p&lt;0.001). Patients experienced epileptic seizures had high rates of sodium-lithium antitransport (&gt; 346 μmol/liter cells x hour) more often than patients without epileptic seizures (52,6% and 35,5%, respectively, &lt;0,05). Patients experienced epileptic seizures with high rates of sodium-lithium antitransport had a higher seizure frequency than patients with low rates of sodium-lithium antitransport. Conclusion: Thus, cortical ischemic brain lesions, significant stenosis of cerebral arteries, predominant perfusion reserve reduction in the posterior cerebral circulation, as well as a high rate of sodium lithium countertransport may be considered as risk factors for post-stroke epilepsy.

Assessment of the brain ischemia during orthostatic stress and lower body negative pressure in air force pilots by near-infrared spectroscopy.

A methodology for the assessment of the cerebral hemodynamic reaction to normotensive hypovolemia, reduction in cerebral perfusion and orthostatic stress leading to ischemic hypoxia and reduced muscular tension is presented. Most frequently, the pilots of highly maneuverable aircraft are exposed to these phenomena. Studies were carried out using the system consisting of a chamber that generates low pressure around the lower part of the body - LBNP (lower body negative pressure) placed on the tilt table. An in-house developed 6-channel NIRS system operating at 735 and 850 nm was used in order to assess the oxygenation of the cerebral cortex, based on measurements of diffusely reflected light in reflectance geometry. The measurements were carried out on a group of 12 active pilots and cadets of the Polish Air Force Academy and 12 healthy volunteers. The dynamics of changes in cerebral oxygenation was evaluated as a response to LBNP stimuli with a simultaneous rapid change of the tilt table angle. Parameters based on calculated changes of total hemoglobin concentration were proposed allowing to evaluate differences in reactions observed in control subjects and pilots/cadets. The results of orthogonal partial least squares-discriminant analysis based on these parameters show that the subjects can be classified into their groups with 100% accuracy.

Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow

Astrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure and activate CNS autonomic sympathetic control circuits to increase systemic arterial blood pressure and heart rate with the purpose of maintaining brain blood flow and oxygen delivery. Studies conducted in experimental animals (laboratory rats) show that astrocytes respond to acute decreases in brain perfusion with elevations in intracellular [Ca2+]. Blockade of Ca2+-dependent signaling mechanisms in populations of astrocytes that reside alongside CNS sympathetic control circuits prevents compensatory increases in sympathetic nerve activity, heart rate and arterial blood pressure induced by reductions in cerebral perfusion. These data suggest that astrocytes function as intracranial baroreceptors and play an important role in homeostatic control of arterial blood pressure and brain blood flow.

Cortical microinfarcts in memory clinic patients are associated with reduced cerebral perfusion

Cerebral cortical microinfarcts (CMIs) are small ischemic lesions associated with cognitive impairment and dementia. CMIs are frequently observed in cortical watershed areas suggesting that hypoperfusion contributes to their development. We investigated if presence of CMIs was related to a decrease in cerebral perfusion, globally or specifically in cortex surrounding CMIs. In 181 memory clinic patients (mean age 72 ± 9 years, 51% male), CMI presence was rated on 3-T magnetic resonance imaging (MRI). Cerebral perfusion was assessed from cortical gray matter of the anterior circulation using pseudo-continuous arterial spin labeling parameters cerebral blood flow (CBF) (perfusion in mL blood/100 g tissue/min) and spatial coefficient of variation (CoV) (reflecting arterial transit time (ATT)). Patients with CMIs had a 12% lower CBF (beta = −.20) and 22% higher spatial CoV (beta = .20) (both p < .05) without a specific regional pattern on voxel-based CBF analysis. CBF in a 2 cm region-of-interest around the CMIs did not differ from CBF in a reference zone in the contralateral hemisphere. These findings show that CMIs in memory clinic patients are primarily related to global reductions in cerebral perfusion, thus shedding new light on the etiology of vascular brain injury in dementia.

Cognitive impairment in patients with arterial hypertension: a relationship with the level and daily blood pressure profile and pathogenetic mechanisms

Arterial hypertension (HT) is one of the main recognized risk factors for the development of cognitive impairment and dementia. The results of most studies indicate that the presence of HT in elderly and senile people is associated with a decrease in cognitive functions and an increased risk of dementia in people of this age group, although some studies have identified the so-called U-shaped curve”. The state of cognitive functions in middle-aged patients with HT has been studied to a much lesser extent, but it has been established that the presence of HT in middle age is associated with deterioration of cognitive functions and an increased risk of dementia in the elderly. In middle-aged hypertensive patients, cognitive impairment affected all cognitive domens, but to a greater extent - neurodynamic indicators of cognitive functions (speech activity, ability to concentrate, speed of cognitive processes). There are few data that levels of systolic blood pressure (BP) during the day, during wakefulness and sleep periods, insufficient night BP decrease, increased daily BP variability, and increased magnitude of the morning BP rise are interrelated with deterioration of the control functions/speed of cognitive processes. Pathogenetic aspects of the relationship of cognitive impairment and HT are diverse and include the hyperactivation of neuro-humoral systems (renin-angiotensin-aldosterone and sympathoadrenal, hypothalamic-pituitary-adrenal system dysfunction, reduction of cerebral perfusion, endothelial dysfunction. Anxiety-depressive disorders are of great importance in the occurrence of cognitive impairment in patients with HT, their interrelation is complex, dualistic, possibly due to a decrease in brain perfusion.

Global brain ischemia in a dog with concurrent multiorgan dysfunction syndrome after bite wound trauma

BackgroundBite wounds are one of the most common traumatic injuries in dogs and depending on their severity, location, etc., urgent care including antibiotic therapy may be necessary. Serious complications can result from these injuries, such as multiple organ dysfunction syndrome (MODS), as well as a generalized reduction in cerebral perfusion, e.g. during cardiac arrest, shock, or severe hypotension that may cause global brain ischemia (GBI).Case presentationA 5-year-old spayed female Maltese dog was presented with generalized seizures, ataxia, and obtunded mentation. The dog was injured by severe bite wounds that penetrated its abdomen and had received blood transfusions, antibiotic therapy (including metronidazole and cefazoline) and underwent emergency surgery 4 days before its visit. Based on a clinical examination, intracranial hypoxic damage with elevated intra-cranial pressure and MODS were highly suspected, and GBI was confirmed following magnetic resonance imaging. Increased signal intensity diffusely distributed in the olfactory bulb and frontal, temporal, and parietal grey matter was evident on the T2-weighted and fluid attenuated inversion recovery transverse images, along with corresponding high signal intensity observed on diffusion weighted imaging. During the 10-month follow-up period, the clinical signs gradually improved, but intermittent circling and cognitive dysfunction deficits remained.ConclusionsGBI should be included among the differential diagnoses in case of any peracute non-progressive neurological dysfunction that occurs with episodes of hypotension or hypoxia. The abnormal signal intensity observed on diffusion weighted imaging was a useful indicator for diagnosing this condition. Long-term medical management with antibiotics and anti-convulsant and anti-oxidant therapies were considered to be helpful in managing the GBI concurrent with MODS in this dog.