Search Results (11)

Hyperbaric oxygenation (HBO₂) can modify gene and protein expression, signaling pathways, and vascular function, leading to altered vasomotor responses. Adenosine receptors (ARs) may mediate these effects by modulating vasoactivity. This study investigated flow-induced dilation (FID) and hypoxia-induced dilation (HID) in the presence or absence of A1R/A2aR agonists (CCPA and CGS-21680, respectively) and antagonists (DPCPX and SCH-58261, respectively) in isolated middle cerebral arteries (MCAs) from Sprague Dawley rats of both sexes and the direct dose-dependent effects of A1R and A2aR agonists on the vascular reactivity of MCAs. Rats were exposed to either acute HBO₂ (Ac-HBO₂) or intermittent HBO₂ over four days (In-HBO₂). Ac-HBO₂ impaired vascular responses to A1R and A2aR agonists and significantly decreased FID and HID. In both Ac-HBO₂ and In-HBO₂, A1R modulation did not significantly affect FID or HID. A2aR stimulation reduced FID in the In-HBO₂ group, while A2aR antagonism had no significant effect on HID. However, the A2aR agonist’s presence enhanced HID in In-HBO₂-exposed rats. Protein expression of A1R and A2aR decreased after Ac-HBO₂, while gene expression increased following In-HBO₂. These findings suggest that ARs play a role in HBO₂-induced vasoreactivity, which possibly changes in MCA, potentially via the modulation of ARs gene and protein expression. Full article

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([^99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = −0.27 and −0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations. Full article

Background: Premature infants are born with immature cerebral autoregulation function and are vulnerable to pressure passive cerebral circulation and subsequent brain injury. Measurements derived from near-infrared spectroscopy (NIRS) have enabled continuous assessment of cerebral vasoreactivity. Although NIRS has enabled a growing field of research, the lack of clear standardization in the field remains problematic. A major limitation of current literature is the absence of a comparative analysis of the different methodologies. Objectives: To determine the relationship between NIRS-derived continuous indices of cerebral autoregulation in a cohort of extremely low birth weight (ELBW) infants. Methods: Premature infants of birth weight 401–1000 g were studied during the first 72 h of life. The cerebral oximetry index (COx), hemoglobin volume index (HVx), and tissue oxygenation heart rate reactivity index (TOHRx) were simultaneously calculated. The relationship between each of the indices was assessed with Pearson correlation. Results: Fifty-eight infants with a median gestational age of 25.8 weeks and a median birth weight of 738 g were included. Intraventricular hemorrhage (IVH) was detected in 33% of individuals. COx and HVx demonstrated the highest degree of correlation, although the relationship was moderate at best (r = 0.543, p < 0.001). No correlation was found either between COx and TOHRx (r = 0.318, p < 0.015) or between HVx and TOHRx (r = 0.287, p < 0.029). No significant differences in these relationships were found with respect to IVH and no IVH in subgroup analysis. Conclusions: COx, HVx, and TOHRx are not numerically equivalent. Caution must be applied when interpreting or comparing results based on different methodologies for measuring cerebral autoregulation. Uniformity regarding data acquisition and analytical methodology are needed to firmly establish a gold standard for neonatal cerebral autoregulation monitoring. Full article

Background: A correlation between worse functional outcomes in Parkinson’s disease (PD) patients with cerebrovascular disease (CVD) or the Akinetic-rigid phenotype has been argued in recent studies. We aimed to evaluate the association of cerebral hemodynamics impairments, assessed by Transcranial Color-coded Doppler sonography (TCCS), on PD patients with different phenotypes of the disease and with risk factors for CVD. Methodology: Idiopathic PD patients (n = 51) were divided into motor subtypes: Akinetic-rigid (AR) (n = 27) and Tremor-dominant (TD) (n = 24) and into two groups regarding vascular risk factors: when ≥2 were present (PDvasc) (n = 18) and <2 (PDnvasc) (n = 33). In a parallel analysis, the Fazekas scale on brain magnetic resonance imaging (MRI) was applied to a sample to assess the degree of leukoaraiosis. TCCS examinations were prospectively performed obtaining middle cerebral artery Mean Flow Velocities (Vm), Resistance Index (RI), and Pulsatility Index (PI). The Breath-Holding Index (BHI) was calculated to assess cerebrovascular reactivity (cVR). Standardized functional scales were administered (UPDRS III and Hoehn&Yahr). Results: The phenotype groups were similar in age, disease duration and demographic parameters, but there were significantly higher H&Y scores than TD group. cVR was impaired in 66.7% of AR vs. 37.5% of TD. AR group exhibited lower BHI (0.53 ± 0.31 vs. 0.91 ± 0.62; p = 0.000), lower Vm after apnea (44.3 ± 9.0 cm/s vs. 53.4 ± 11.4 cm/s; p = 0.003), higher PI (0.91 ± 0.26 vs. 0.76 ± 0.12; p = 0.000) and RI (0.58 ± 0.11 vs. 0.52 ± 0.06; p = 0.021). PDvasc group showed higher PI (0.98 vs. 0.76; p = 0.001) and higher frequency of altered cVR (72.2% vs. 42.2%; p = 0.004). There was a significant predominance of higher values on Fazekas scale in the PDvasc group. We found no difference between the Fazekas scale when comparing motor subtypes groups but there was a trend toward higher scores in the AR phenotype. Conclusions: TCCS, a cost-effective method, displayed impaired cVR in Parkinsonian patients with risk factors for CVD with higher degree of MRI leukoaraiosis. PD patients with the AR disease phenotype also presented impaired cVR on TCCS and greater functional impairment, although with just a trend to higher scores on MRI Fazekas. Full article

Carotid artery stenosis (CAS) is a common vascular disease with long-term consequences for the brain. Although CAS is strongly associated with impaired cerebral hemodynamics and neurodegeneration, the mechanisms underlying hemodynamic impairment in the microvasculature remain unknown. In this work, we employed functional near-infrared spectroscopy (fNIRS) to introduce a methodological approach for quantifying the temporal delay of the evoked hemodynamic response. The method was validated during a vasodilatory task (breath-holding) in 50 CAS patients and 20 controls. Our results suggest that the hemodynamic response to breath-holding can be delayed by up to 6 s in the most severe patients, a significant increase from the median 4 s measured for the control group (p = 0.01). In addition, the fraction of brain regions that responded to the task decreased as the CAS severity increased, from a median of 90% in controls to 73% in the most severe CAS group (p = 0.04). The presence of collateral circulation increases the response to breath-holding and decreases the average time delays across the brain, although the number of communicating arteries alone cannot predict these fNIRS-based hemodynamic variables (p > 0.09). Overall, this work proposes a method to quantitatively assess impaired cerebral hemodynamics in CAS patients. Full article

Organism survival depends on oxygen delivery and utilization to maintain the balance of energy and toxic oxidants production. This regulation is crucial to the brain, especially after acute injuries. Secondary insults after brain damage may include impaired cerebral metabolism, ischemia, intracranial hypertension and oxygen concentration disturbances such as hypoxia or hyperoxia. Recent data highlight the important role of clinical protocols in improving oxygen delivery and resulting in lower mortality in brain-injured patients. Clinical protocols guide the rules for oxygen supplementation based on physiological processes such as elevation of oxygen supply (by mean arterial pressure (MAP) and intracranial pressure (ICP) modulation, cerebral vasoreactivity, oxygen capacity) and reduction of oxygen demand (by pharmacological sedation and coma or hypothermia). The aim of this review is to discuss oxygen metabolism in the brain under different conditions. Full article

In addition to respiratory symptoms, COVID-19 often causes damage to many other organs, especially in severe forms of the disease. Long-term consequences after COVID-19 are common and often have neurological symptoms. Cerebral vasoreactivity may be impaired after acute COVID-19 and in our study, we wanted to show how constant and reversible are the changes in brain vasoreactivity after infection. This cross-sectional observational study included 49 patients diagnosed with COVID-19 and mild neurological symptoms 300 days after the onset of the disease. We used a transcranial color-coded Doppler (TCCD) and a breath-holding test (BHT) to examine cerebral vasoreactivity and brain endothelial function. We analyzed the parameters of the flow rate through the middle cerebral artery (MCA): peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), resistance index (RI) and pulsatility index (PI), and we calculated the breath-holding index (BHI). Subjects after COVID-19 infection had lower measured velocity parameters through MCA at rest period and after BHT, lower relative increases of flow velocities after BHT, and lower BHI. We showed that subjects, 300 days after COVID-19, still have impaired cerebral vasoreactivity measured by TCCD and they have chronic endothelial dysfunction. Full article

From the beginning of the SARS-CoV-2 virus pandemic, it was clear that the virus is highly neurotrophic. Neurological manifestations can range from nonspecific symptoms such as dizziness, headaches and olfactory disturbances to severe forms of neurological dysfunction. Some neurological complication can occur even after mild forms of respiratory disease. This study’s aims were to assess cerebrovascular reactivity in patients with nonspecific neurological symptoms after SARS-CoV-2 infection. A total of 25 patients, aged 33–62 years, who had nonspecific neurological symptoms after SARS-CoV-2 infection, as well as 25 healthy participants in the control group, were assessed for cerebrovascular reactivity according to transcranial color Doppler (TCCD) which we combined with a breath-holding test (BHT). In subjects after SARS-CoV-2 infection, there were statistically significantly lower flow velocities through the middle cerebral artery at rest period, lower maximum velocities at the end of the breath-holding period and lower breath holding index (BHI) in relation to the control group. Changes in cerebral artery flow rate velocities indicate poor cerebral vasoreactivity in the group after SARS-CoV-2 infection in regard to the control group and suggest vascular endothelial damage by the SARS-CoV-2 virus. Full article

Ubiquinol can protect endothelial cells from multiple mechanisms that cause endothelial damage and vascular dysfunction, thus contributing to dementia. A total of 69 participants diagnosed with mild cognitive impairment (MCI) received either 200 mg/day ubiquinol (Ub) or placebo for 1 year. Cognitive assessment of patients was performed at baseline and after 1 year of follow-up. Patients’ cerebral vasoreactivity was examined using transcranial Doppler sonography, and levels of Ub and lipopolysaccharide (LPS) in plasma samples were quantified. Cell viability and necrotic cell death were determined using the microvascular endothelial cell line bEnd3. Coenzyme Q10 (CoQ) levels increased in patients supplemented for 1 year with ubiquinol versus baseline and the placebo group, although higher levels were observed in male patients. The higher cCoQ concentration in male patients improved cerebral vasoreactivity CRV and reduced inflammation, although the effect of Ub supplementation on neurological improvement was negligible in this study. Furthermore, plasma from Ub-supplemented patients improved the viability of endothelial cells, although only in T2DM and hypertensive patients. This suggests that ubiquinol supplementation could be recommended to reach a concentration of 5 μg/mL in plasma in MCI patients as a complement to conventional treatment. Full article

The poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 has been reported to improve endothelial dysfunction in the peripheral system. We addressed the role of PJ34 on the vascular tone and vasoreactivity during development in the mouse brain. Blood flows were measured in the basilar trunk using ultrasonography. Cerebral vasoreactivity or vasodilation reserve was estimated as a percentage increase in mean blood flow velocities (mBFV) recorded under normoxia-hypercapnia in control and after PJ34 administration. Non-selective and selective eNOS and nNOS inhibitors were used to evaluate the role of NO-pathway into the hemodynamic effects of PJ34. PJ34 increased mBFVs from 15.8 ± 1.6 to 19.1 ± 1.9 cm/s (p = 0.0043) in neonatal, from 14.6 ± 1.4 to 16.1 ± 0.9 cm/s (p = 0.0049) in adult, and from 15.7 ± 1.7 to 17.5 ± 2.0 cm/s (p = 0.0024) in aged mice 48 h after administration. These PJ34 values were similar to those measured in age-matched control mice under normoxia-hypercapnia. This recruitment was mediated through the activation of constitutive NO synthases in both the neonatal (38.2 ± 6.7 nmol/min/mg protein) and adult (31.5 ± 4.4 nmol/min/mg protein) brain, as compared to age-matched control brain (6.9 ± 0.4 and 6.3 ± 0.7 nmol/min/mg protein), respectively. In addition, quite selective eNOS inhibitor was able to inhibit the recruitment. PJ34 by itself is able to increase cerebral blood flow through the NO-pathway activation at least over 48 h after a single administration. Full article

Background: Fabry disease (FD) causes cerebrovascular disease (CVD) even if asymptomatic, and this is why it is important to identify non-invasive methods to monitor the disease. We evaluated the usefulness of the cerebral autoregulation, vasoreactivity, and neurovascular coupling assessed by transcranial Doppler (TCD) in FD. Methods: Ten adult patients with classic phenotype FD, without clinical expression of CVD, and ten healthy controls, were included. We monitored cerebral blood flow velocity with TCD in the middle and posterior cerebral arteries, blood pressure, heart rate, and non-invasive expired carbon dioxide (CO₂). Cerebral autoregulation was calculated from the spontaneous oscillations of blood pressure, cerebral vasoreactivity through CO₂ inhalation and hyperventilation and neurovascular coupling by the flow velocity change to visual stimulation. Results: FD male patients showed blunted vasoreactivity in posterior circulation (0.70 ± 0.36%/mmHg vs. 1.09 ± 0.18%/mmHg CO₂, p = 0.01) and impaired neurovascular coupling (overshoot 15 ± 2.9% vs. 28 ± 6.1%, p < 0.01). Cerebral autoregulation was similar to controls. Conclusion: Male patients with FD classic phenotype and hitherto clinical expression of CVD already show impairment of cerebral vasoreactivity and neurovascular coupling. It supports the notion of an early dysfunction of cerebral microvascular in a presymptomatic stage of CVD in FD and that TCD could be useful in its assessment. Full article