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1.
Neuron ; 112(9): 1378-1380, 2024 May 01.
Article En | MEDLINE | ID: mdl-38697020

Adequate reperfusion after ischemic stroke is a major determinant of functional outcome yet remains unpredictable and insufficient for most survivors. In this issue of Neuron, Binder et al.1 identify leptomeningeal collaterals (LMCs) in mice and human patients as a key factor in regulating reperfusion and hemorrhagic transformation following stroke.


Collateral Circulation , Reperfusion , Stroke , Humans , Animals , Stroke/physiopathology , Collateral Circulation/physiology , Mice , Ischemic Stroke/physiopathology , Cerebrovascular Circulation/physiology , Meninges/blood supply , Brain Ischemia/physiopathology
2.
Nat Commun ; 15(1): 3987, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734698

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.


Blood-Brain Barrier , Brain , Cerebrovascular Circulation , Nanoparticles , Vinca Alkaloids , Animals , Vinca Alkaloids/pharmacology , Vinca Alkaloids/pharmacokinetics , Vinca Alkaloids/administration & dosage , Vinca Alkaloids/chemistry , Nanoparticles/chemistry , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Mice , Cerebrovascular Circulation/drug effects , Male , Brain/metabolism , Brain/drug effects , Brain/blood supply , Humans , Neuroprotective Agents/pharmacokinetics , Neuroprotective Agents/pharmacology , Mice, Inbred C57BL , Tissue Distribution , Drug Delivery Systems , Mice, Transgenic
3.
Sci Rep ; 14(1): 10024, 2024 05 01.
Article En | MEDLINE | ID: mdl-38693311

Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 [42.3-132.7] vs. 13.5 [5.0-34.1] mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 [1-4] vs. 2 [0-3]; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: ß = 0.176, p = 0.034; direct effect: ß = 0.045, p = 0.64; indirect effect: ß = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.


Cerebrovascular Circulation , Endovascular Procedures , Ischemic Stroke , Thrombectomy , Humans , Thrombectomy/methods , Thrombectomy/adverse effects , Male , Female , Aged , Ischemic Stroke/surgery , Endovascular Procedures/methods , Middle Aged , Treatment Outcome , Aged, 80 and over , Retrospective Studies
4.
CNS Neurosci Ther ; 30(5): e14748, 2024 May.
Article En | MEDLINE | ID: mdl-38727518

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.


Homeostasis , Ischemic Stroke , Thrombolytic Therapy , Humans , Male , Female , Aged , Middle Aged , Prognosis , Thrombolytic Therapy/methods , Homeostasis/physiology , Homeostasis/drug effects , Ischemic Stroke/drug therapy , Ischemic Stroke/physiopathology , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Cerebrovascular Circulation/physiology , Cerebrovascular Circulation/drug effects , Prospective Studies , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use , Administration, Intravenous , Predictive Value of Tests , Aged, 80 and over , Nomograms , Stroke/drug therapy , Stroke/physiopathology
6.
BMC Cardiovasc Disord ; 24(1): 239, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714966

OBJECTIVE: Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes. METHODS: The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated. RESULTS: A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h. CONCLUSION: This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications. TRIAL REGISTRATION: The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023.


Aortic Aneurysm , Aortic Dissection , Cerebrovascular Circulation , Humans , Aortic Dissection/surgery , Aortic Dissection/mortality , Aortic Dissection/complications , Aortic Dissection/physiopathology , Aortic Dissection/diagnostic imaging , Treatment Outcome , Risk Factors , Time Factors , Aortic Aneurysm/surgery , Aortic Aneurysm/mortality , Aortic Aneurysm/complications , Aortic Aneurysm/physiopathology , Aortic Aneurysm/diagnostic imaging , Female , Male , Middle Aged , Aged , Acute Disease , Cerebrovascular Disorders/surgery , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/mortality , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/physiopathology , Adult , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Risk Assessment , Reperfusion , Time-to-Treatment
7.
J Med Case Rep ; 18(1): 226, 2024 May 08.
Article En | MEDLINE | ID: mdl-38715146

BACKGROUND: Perioperative symptomatic carotid artery occlusion after carotid endarterectomy is a rare complication. In this study, we present a case of symptomatic acute carotid artery occlusion that occurred after carotid endarterectomy in a patient with coexistent subclavian artery steal phenomenon, which was successfully treated with subclavian artery stenting. CASE PRESENTATION: A 57-year-old East Asian female presented with stenosis in the left common carotid artery and left subclavian artery along with subclavian steal. The proximal segment of the left anterior cerebral artery was hypoplastic, and the posterior communicating arteries on both sides were well-developed. Left internal carotid artery stenosis progressed during the follow-up examination; therefore, left carotid endarterectomy was performed. On the following day, symptoms of cerebral perfusion deficiency appeared due to occlusion of the left carotid artery. The stenotic origin of the left common carotid artery and the suspected massive thrombus in the left carotid artery posed challenges to carotid revascularization. Therefore, left subclavian artery stenting for the subclavian steal phenomenon was determined to be the best option for restoring cerebral blood flow to the whole brain. Her symptoms improved after the procedure, and the postprocedural workup revealed improved cerebral blood flow. CONCLUSION: Subclavian artery stenting is safe and may be helpful in patients with cerebral perfusion deficiency caused by intractable acute carotid occlusion coexisting with the subclavian steal phenomenon. Revascularization of asymptomatic subclavian artery stenosis is generally not recommended. However, cerebral circulatory insufficiency as a comorbidity may be worth considering.


Carotid Stenosis , Cerebrovascular Circulation , Endarterectomy, Carotid , Stents , Subclavian Steal Syndrome , Humans , Female , Subclavian Steal Syndrome/surgery , Middle Aged , Carotid Stenosis/surgery , Treatment Outcome , Subclavian Artery/surgery , Postoperative Complications/surgery , Postoperative Complications/etiology
8.
J Biomed Opt ; 29(Suppl 3): S33302, 2024 Jun.
Article En | MEDLINE | ID: mdl-38707651

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. Results: In the first protocol (28±5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients (65±15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.


Cerebrovascular Circulation , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/instrumentation , Female , Male , Adult , Cerebrovascular Circulation/physiology , Hemodynamics/physiology , Oximetry/methods , Oximetry/instrumentation , Oxygen/blood , Oxygen/metabolism , Brain/diagnostic imaging , Brain/blood supply , Equipment Design
9.
Crit Care Explor ; 6(5): e1083, 2024 May.
Article En | MEDLINE | ID: mdl-38694846

OBJECTIVES: This prospective cohort study aimed to investigate changes in intracranial pressure (ICP) and cerebral hemodynamics in infants with congenital heart disease undergoing the Glenn procedure, focusing on the relationship between superior vena cava pressure and estimated ICP. DESIGN: A single-center prospective cohort study. SETTING: The study was conducted in a cardiac center over 4 years (2019-2022). PATIENTS: Twenty-seven infants with congenital heart disease scheduled for the Glenn procedure were included in the study, and detailed patient demographics and primary diagnoses were recorded. INTERVENTIONS: Transcranial Doppler (TCD) ultrasound examinations were performed at three time points: baseline (preoperatively), postoperative while ventilated (within 24-48 hr), and at discharge. TCD parameters, blood pressure, and pulmonary artery pressure were measured. MEASUREMENTS AND MAIN RESULTS: TCD parameters included systolic flow velocity, diastolic flow velocity (dFV), mean flow velocity (mFV), pulsatility index (PI), and resistance index. Estimated ICP and cerebral perfusion pressure (CPP) were calculated using established formulas. There was a significant postoperative increase in estimated ICP from 11 mm Hg (interquartile range [IQR], 10-16 mm Hg) to 15 mm Hg (IQR, 12-21 mm Hg) postoperatively (p = 0.002) with a trend toward higher CPP from 22 mm Hg (IQR, 14-30 mm Hg) to 28 mm Hg (IQR, 22-38 mm Hg) postoperatively (p = 0.1). TCD indices reflected alterations in cerebral hemodynamics, including decreased dFV and mFV and increased PI. Intracranial hemodynamics while on positive airway pressure and after extubation were similar. CONCLUSIONS: Glenn procedure substantially increases estimated ICP while showing a trend toward higher CPP. These findings underscore the intricate interaction between venous pressure and cerebral hemodynamics in infants undergoing the Glenn procedure. They also highlight the remarkable complexity of cerebrovascular autoregulation in maintaining stable brain perfusion under these circumstances.


Cerebrovascular Circulation , Heart Defects, Congenital , Hemodynamics , Intracranial Pressure , Ultrasonography, Doppler, Transcranial , Humans , Infant , Prospective Studies , Female , Male , Intracranial Pressure/physiology , Heart Defects, Congenital/surgery , Heart Defects, Congenital/physiopathology , Heart Defects, Congenital/diagnostic imaging , Cerebrovascular Circulation/physiology , Ultrasonography, Doppler, Transcranial/methods , Hemodynamics/physiology , Cohort Studies , Fontan Procedure , Vena Cava, Superior/physiopathology , Vena Cava, Superior/diagnostic imaging
10.
Sci Rep ; 14(1): 7700, 2024 04 02.
Article En | MEDLINE | ID: mdl-38565588

Mechanical thrombectomy (MT) is the current standard treatment for strokes in the anterior cerebral circulation (AMT) and has recently been proven to be beneficial in the posterior circulation strokes (PMT). Our study aims to evaluate parameters for favorable outcomes in PMT-patients and to compare the clinical characteristics of individuals who received AMT and PMT. For this purpose, we confronted AMT and PMT-receipients and performed a multivariate regression analysis to assess the influence of factors on favorable outcomes in the study group and in the AMT and PMT subgroups. When analysing 623 MT-patients, those who received PMT had significantly lower admission National Institutes of Health Stroke Scale (NIHSS) scores (9 vs. 13; p < 0.001) and 24 h post-MT (7 vs. 12; p = 0.006). Key parameters influencing the favorable outcomes of PMT at discharge and at 90th day include: NIHSS scores (OR: 0.865, 95% CI: 0.813-0.893, and OR: 0.900, 95% CI: 0.861-0.925), MT time (OR: 0.993, 95% CI: 0.987-0.998 and OR: 0.993, 95% CI: 0.990-0.997), and leukocytosis (OR: 0.961, 95% CI: 0.928-0.988 and OR: 0.974, 95% CI: 0.957-0.998). Different clinical profiles exist between AMT and PMT-recipients, with the neurological status post-MT being decisive for the prognosis. Several factors play an important role in predicting outcome, especially in the PMT group.


Brain Ischemia , Stroke , Humans , Thrombectomy/adverse effects , Treatment Outcome , Stroke/surgery , Stroke/etiology , Prognosis , Cerebrovascular Circulation , Retrospective Studies , Brain Ischemia/etiology
11.
Commun Biol ; 7(1): 404, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38570584

Mechanisms to modulate cerebrovascular tone are numerous, interconnected, and spatially dependent, increasing the complexity of experimental study design, interpretation of action-effect pathways, and mechanistic modelling. This difficulty is exacerbated when there is an incomplete understanding of these pathways. We propose interaction graphs to break down this complexity, while still maintaining a holistic view of mechanisms to modulate cerebrovascular tone. These graphs highlight the competing processes of neurovascular coupling, cerebral autoregulation, and cerebral reactivity. Subsequent analysis of these interaction graphs provides new insights and suggest potential directions for research on neurovascular coupling, modelling, and dementia.


Cerebrovascular Circulation , Neurovascular Coupling , Cerebrovascular Circulation/physiology , Homeostasis/physiology
12.
Sci Rep ; 14(1): 8476, 2024 04 11.
Article En | MEDLINE | ID: mdl-38605063

Computational fluid dynamics (CFD) has been utilized to calculate hemodynamic parameters in anterior communicating artery aneurysm (AComA), which is located at a junction between left and right A1 and A2 segments. However, complete or half circle of Willis (CoW) models are used indiscriminately. This study aims to suggest recommendations for determining suitable CoW model. Five patient-specific CoW models with AComA were used, and each model was divided into complete, left-half, and right-half models. After validating the CFD using a flow experiment, the hemodynamic parameters and flow patterns in five AComAs were compared. In four out of five cases, inflow from one A1 side had a dominant influence on the AComA, while both left and right A1 sides affected the AComA in the remaining case. Also, the average difference in time-averaged wall shear stress between the complete and half models for four cases was 4.6%, but it was 62% in the other case. The differences in the vascular resistances of left and right A1 and A2 segments greatly influenced the flow patterns in the AComA. These results may help to enhance clinicians' understanding of blood flow in the brain, leading to improvements in diagnosis and treatment of cerebral aneurysms.


Intracranial Aneurysm , Humans , Circle of Willis , Hemodynamics/physiology , Cerebrovascular Circulation/physiology , Brain
13.
BMC Pregnancy Childbirth ; 24(1): 263, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38605299

BACKGROUND: Children exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development. STUDY DESIGN: To determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12-15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure). RESULTS: All drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%). CONCLUSIONS: Fetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.


Cannabinoids , Perinatal Death , Pregnancy , Mice , Female , Animals , Child , Humans , Cannabinoids/adverse effects , Perinatal Mortality , Ethanol/adverse effects , Fetus/blood supply , Disease Models, Animal , Cerebrovascular Circulation
14.
Alzheimers Res Ther ; 16(1): 80, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38610005

BACKGROUND: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. METHODS: A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. RESULTS: No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC. CONCLUSIONS: Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT04436341).


Alzheimer Disease , Epilepsy , Humans , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Hippocampus/diagnostic imaging , Temporal Lobe , Cerebrovascular Circulation , Epilepsy/diagnostic imaging
15.
Int J Mol Sci ; 25(7)2024 Mar 22.
Article En | MEDLINE | ID: mdl-38612392

The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.9 PSI/131 kPa peak pressure, 10.95 ms duration, and 70.26 PSI·ms/484.42 kPa·ms impulse) BOP exposure in rats. A significant reduction in the density of the glycocalyx was observed 2-3 h, 1-, and 3 days after the blast exposure. The glycocalyx recovered by 28 days after exposure and was associated with an increase in HS (14 and 28 days) and in HSPG/syndecan-2 and CS (28 days) in the frontal cortex. In separate experiments, we observed significant decreases in CBF and a diminished response to hypercapnia at all time points with some recovery at 3 days. Given the role of the glycocalyx in regulating physiological function of the cerebral vasculature, damage to the glycocalyx after BOP exposure may result in the onset of pathogenesis and progression of cerebrovascular dysfunction leading to neuropathology.


Heparan Sulfate Proteoglycans , Syndecan-2 , Animals , Rats , Glycocalyx , Hypercapnia , Cerebrovascular Circulation , Heparitin Sulfate , Chondroitin Sulfates
16.
Acta Neurochir (Wien) ; 166(1): 190, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38653934

BACKGROUND: Cerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt). METHODS: Retrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio. RESULTS: Median age was 16 years (range 8-17) and median Glasgow coma scale motor score 5 (range 2-5). Both lactate (p = 0.010) and LPR (p = < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p = < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < -10. CONCLUSIONS: Increased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.


Brain Injuries, Traumatic , Cerebrovascular Circulation , Homeostasis , Intracranial Pressure , Lactic Acid , Humans , Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/metabolism , Child , Adolescent , Homeostasis/physiology , Female , Male , Retrospective Studies , Intracranial Pressure/physiology , Cerebrovascular Circulation/physiology , Lactic Acid/metabolism , Lactic Acid/analysis , Microdialysis/methods , Pyruvic Acid/metabolism , Pyruvic Acid/analysis , Brain/metabolism , Brain/physiopathology
17.
BMC Neurol ; 24(1): 128, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627680

OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.


Motor Cortex , Restless Legs Syndrome , Humans , Restless Legs Syndrome/epidemiology , Cross-Sectional Studies , Case-Control Studies , Renal Dialysis/adverse effects , Cerebrovascular Circulation/physiology , Iron , Magnetic Resonance Imaging
18.
Curr Med Imaging ; 20: e15734056219963, 2024.
Article En | MEDLINE | ID: mdl-38660947

BACKGROUND: A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. METHODS: We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. RESULTS: Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). CONCLUSION: The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.


Cerebrovascular Circulation , Migraine Disorders , Spin Labels , Humans , Cerebrovascular Circulation/physiology , Migraine Disorders/diagnostic imaging , Migraine Disorders/physiopathology , Female , Adult , Male , Imaging, Three-Dimensional/methods , Chronic Disease , Middle Aged , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/blood supply , Brain/physiopathology , Case-Control Studies , Gray Matter/diagnostic imaging , Gray Matter/blood supply
19.
Physiol Meas ; 45(4)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38569522

Objective. The continuous delivery of oxygen is critical to sustain brain function, and therefore, measuring brain oxygen consumption can provide vital physiological insight. In this work, we examine the impact of calibration and cerebral blood flow (CBF) measurements on the computation of the relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2) from hemoglobin-sensitive intrinsic optical imaging data. Using these data, we calculate rCMRO2, and calibrate the model using an isometabolic stimulus.Approach. We used awake head-fixed rodents to obtain hemoglobin-sensitive optical imaging data to test different calibrated and uncalibrated rCMRO2models. Hypercapnia was used for calibration and whisker stimulation was used to test the impact of calibration.Main results. We found that typical uncalibrated models can provide reasonable estimates of rCMRO2with differences as small as 7%-9% compared to their calibrated models. However, calibrated models showed lower variability and less dependence on baseline hemoglobin concentrations. Lastly, we found that supplying the model with measurements of CBF significantly reduced error and variability in rCMRO2change calculations.Significance. The effect of calibration on rCMRO2calculations remains understudied, and we systematically evaluated different rCMRO2calculation scenarios that consider including different measurement combinations. This study provides a quantitative comparison of these scenarios to evaluate trade-offs that can be vital to the design of blood oxygenation sensitive imaging experiments for rCMRO2calculation.


Brain , Optical Imaging , Oxygen Consumption , Oxygen , Wakefulness , Animals , Calibration , Mice , Brain/metabolism , Brain/diagnostic imaging , Brain/blood supply , Oxygen/metabolism , Wakefulness/physiology , Oxygen Consumption/physiology , Cerebrovascular Circulation/physiology , Hemoglobins/metabolism , Hemoglobins/analysis , Male , Mice, Inbred C57BL , Hypercapnia/metabolism , Hypercapnia/diagnostic imaging
20.
Cereb Cortex ; 34(4)2024 Apr 01.
Article En | MEDLINE | ID: mdl-38602740

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30 min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.


Executive Function , Exercise , Humans , Memory, Short-Term , Cerebrovascular Circulation , Dorsolateral Prefrontal Cortex
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