UNASSIGNED: Pravastatin sodium is reported to have multiple beneficial effects in cerebral atherosclerosis and neuronal injury; however, the preventive effects on cerebral venous ischemia are still unknown. Herein, we aimed to examine the neuroprotective effects of transoral prior administration of pravastatin sodium against cerebral cortical venous ischemia with suppression of apoptosis.
UNASSIGNED: Thirty 8-week-old male Wistar rats were divided equally into two study groups (n = 15 vs. n = 15); the pravastatin group was fed 1% pravastatin sodium with their usual diet for 2 weeks, while the control group only received the usual diet. Two-vein occlusion (2VO) model was applied for this study, and two adjacent cortical veins in each animal were permanently occluded photochemically with rose bengal dye. During photo-thrombosis, regional changes of the cerebral blood flow (CBF) in area of the venous ischemia were recorded. At 48-h after 2VO, animals were euthanized using perfusion fixation, and we histologically measured ratios of infarcted area to contralateral hemisphere, and counted Bax- and Bcl-2-positive cells in the penumbra to investigate the implications for apoptosis.
UNASSIGNED: The ratio of infarcted area was significantly decreased in the pravastatin group compared to the control group (P < 0.01). The number of Bax-positive cells also decreased significantly in the pravastatin group (P < 0.01). In contrast, immunolabeling for Bcl-2 was essentially negative in all areas in both groups. There were also no significant differences in regional CBF changes after 2VO between the two groups (P = 0.13).
UNASSIGNED: Pre-emptive administration of pravastatin sodium mixed in the food has neuroprotective effects against cerebral cortical venous ischemia with suppression of apoptosis associated with inhibition of Bax expression but has little influence on regional CBF.

UNASSIGNED: We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative T 2 \' mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD).
UNASSIGNED: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional 31P MRSI and oxygenation-sensitive quantitative T 2 \' mapping (1/ T 2 \'  = 1/T2* - 1/T2) at 3 Tesla (T). PHi was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T 2 \' values were averaged across the entire white matter (WM). Furthermore, T 2 \' values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls.
UNASSIGNED: Quantitative T 2 \' values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 ± 16.94 vs. 138.19 ± 12.66 ms and 147.45 ± 18.14 vs. 137.99 ± 12.19 ms, p < 0.05). WM T 2 \' values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased T 2 \' was significantly associated with more alkaline pHi (ρ=0.299, p < 0.05). Both T 2 \' and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p = 0.001 and ρ=0.452, p = 0.016).
UNASSIGNED: This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

UNASSIGNED: Regular Baduanjin exercise training has been shown to be beneficial to the physical and cognitive health of older adults, but the underlying mechanisms remain to be investigated. This study examined the influence of Baduanjin on cerebral hemodynamics in community-dwelling older adults with cognitive frailty.
UNASSIGNED: Randomized controlled trial.
UNASSIGNED: A total of 102 eligible participants were randomly allocated into the Baduanjin exercise intervention group (BEG) or usual physical activity control group (CG) for 24 weeks. Cerebral hemodynamic parameters of bilateral middle/anterior cerebral artery and basilar artery, cognitive ability and physical frailty were assessed using Transcranial Doppler (TCD), Montreal Cognitive Assessment (MoCA) and Edmonton Frailty Scale (EFS) at baseline and 24 weeks post-intervention.
UNASSIGNED: After 24 weeks intervention, the changes in peak systolic velocity (PSV), mean blood flow velocity (MBFV), and end diastolic velocity (EDV) in the right middle cerebral artery and basilar artery were better in the BEG than in the CG; the increase in MoCA scores and the decrease in EFS scores were significantly higher in the BEG than in the CG. Moreover, the interaction of exercise and time on those variables showed obvious significance.
UNASSIGNED: The 24 weeks Baduanjin exercise training had a positive beneficial effect on cerebral blood flow in community-dwelling older adults with cognitive frailty. This may be a potential mechanism by which Baduanjin exercise improves the cognitive frailty in older adults.
UNASSIGNED: Chinese Clinical Trial Registry, ChiCTR1800020341.
UNASSIGNED: December 25, 2018, http://www.chictr.org.cn/showproj.aspx?proj=29846.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare chronic central-nervous-system inflammatory disorder that became known only recently, and the pathogenesis of CLIPPERS remains poorly understood. This report presents clinical and radiological features of a rare case: a young female patient who rapidly died of suspected CLIPPERS. Helpful multiparametric MRI diagnostic criteria are proposed that can help discriminate CLIPPERS from non-CLIPPERS pathologies. We reviewed clinical history, symptoms, quantitative data from brain multiparametric MRI before and after treatment, and histopathological data. Perfusion-weighted imaging revealed a decrease in regional cerebral blood flow by 31% and in cerebral blood volume by 64%, with a moderate increase in transit time and in time to peak by up to 23% in affected pontine and cerebral white matter. As estimated by diffusion tensor imaging, there was elevated density of tracts (n/mm2) and a decrease of fraction anisotropy (×10-3 mm/s2) in the patient\'s pons as compared to a healthy control: density of tracts = 13.5 vs 12.4 and fraction anisotropy = 0.32 vs 0.45, respectively. Macromolecular proton fraction values proved to be reduced (15.8% and 14.5% in the control, respectively) in the patient\'s cerebral peduncles by 3% and in the pons by 4.1% and in a periventricular white matter lesion by 6.4% (11.3% in the normal-looking contralateral hemisphere). Based on our findings, we argue that quantitative MRI techniques may be a valuable source of biomarkers and reliable diagnostic criteria and can shed light on the pathogenesis and exact nosological position of this disorder.

UNASSIGNED: Sporadic cerebral small vessel disease (SVD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) share clinical and neuroimaging features and possibly vascular dysfunction(s). However few studies have included both conditions, assessed more than one vascular dysfunction simultaneously, or included more than one centre. The INVESTIGATE-SVDs study will assess several cerebrovascular dysfunctions with MRI in participants with sporadic SVD or CADASIL at three European centres.
UNASSIGNED: We will recruit participants with sporadic SVDs (ischaemic stroke or vascular cognitive impairment) and CADASIL in Edinburgh, Maastricht and Munich. We will perform detailed clinical and neuropsychological phenotyping of the participants, and neuroimaging including structural MRI, cerebrovascular reactivity MRI (CVR: using carbon dioxide challenge), phase contrast MRI (arterial, venous and CSF flow and pulsatility), dynamic contrast-enhanced MRI (blood brain barrier (BBB) leakage) and multishell diffusion imaging. Participants will measure their blood pressure (BP) and its variability over seven days using a telemetric device.
UNASSIGNED: INVESTIGATE-SVDs will assess the relationships of BBB integrity, CVR, pulsatility and CSF flow in sporadic SVD and CADASIL using a multisite, multimodal MRI protocol. We aim to establish associations between these measures of vascular function, risk factors particularly BP and its variability, and brain parenchymal lesions in these two SVD phenotypes. Additionally we will test feasibility of complex multisite MRI, provide reliable intermediary outcome measures and sample size estimates for future trials.

UNASSIGNED: Increased plasma ammonia concentration and consequent disruption of brain energy metabolism could underpin the pathogenesis of hepatic encephalopathy (HE). Brain energy homeostasis relies on effective maintenance of brain oxygenation, and dysregulation impairs neuronal function leading to cognitive impairment. We hypothesised that HE is associated with reduced brain oxygenation and we explored the potential role of ammonia as an underlying pathophysiological factor.
UNASSIGNED: In a rat model of chronic liver disease with minimal HE (mHE; bile duct ligation [BDL]), brain tissue oxygen measurement, and proton magnetic resonance spectroscopy were used to investigate how hyperammonaemia impacts oxygenation and metabolic substrate availability in the central nervous system. Ornithine phenylacetate (OP, OCR-002; Ocera Therapeutics, CA, USA) was used as an experimental treatment to reduce plasma ammonia concentration.
UNASSIGNED: In BDL animals, glucose, lactate, and tissue oxygen concentration in the cerebral cortex were significantly lower than those in sham-operated controls. OP treatment corrected the hyperammonaemia and restored brain tissue oxygen. Although BDL animals were hypotensive, cortical tissue oxygen concentration was significantly improved by treatments that increased arterial blood pressure. Cerebrovascular reactivity to exogenously applied CO2 was found to be normal in BDL animals.
UNASSIGNED: These data suggest that hyperammonaemia significantly decreases cortical oxygenation, potentially compromising brain energy metabolism. These findings have potential clinical implications for the treatment of patients with mHE.
UNASSIGNED: Brain dysfunction is a serious complication of cirrhosis and affects approximately 30% of these patients; however, its treatment continues to be an unmet clinical need. This study shows that oxygen concentration in the brain of an animal model of cirrhosis is markedly reduced. Low arterial blood pressure and increased ammonia (a neurotoxin that accumulates in patients with liver failure) are shown to be the main underlying causes. Experimental correction of these abnormalities restored oxygen concentration in the brain, suggesting potential therapeutic avenues to explore.

UNASSIGNED: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice.
UNASSIGNED: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and pole-climbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i.
UNASSIGNED: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells.
UNASSIGNED: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

COVID-19 infection was mainly associated with respiratory symptoms, but lately, ischemic stroke (IS) has been reported in several cases. The incidence of IS in SARS-CoV-2 infection is increasing, and its mechanism is still not fully understood. Calcitonin gene-related peptide (CGRP) -the abundantly expressed protein in the peripheral and central nervous system- showed low expression in SARS-CoV-2 patients. This peptide is strongly implicated in regulating cerebral blood flow (CBF) and improving neurological deficits after cerebral arterial occlusion. We assume that a possible interplay between the low circulating levels of CGRP may affect CBF, thus worsening the symptoms of IS in SARS-CoV-2 patients.

UNASSIGNED: Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients.
UNASSIGNED: 60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 min post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound).
UNASSIGNED: End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥ 30 mmHg) versus hypocapnia (end-tidal PCO2 < 30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all < 0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients.
UNASSIGNED: During tilt testing, extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients.
UNASSIGNED: The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.

Hepatic encephalopathy (HE) following acute and chronic liver failure is defined as a complex of neuropsychiatric abnormalities, such as discrete personal changes, sleep disorder, forgetfulness, confusion, and decreasing the level of consciousness to coma. The use and design of suitable animal models that represent clinical features and pathological changes of HE are valuable to map the molecular mechanisms that result in HE. Among different types of animal models, thioacetamide (TAA) has been used extensively for the induction of acute liver injury and HE. This agent is not directly hepatotoxic but its metabolites induce liver injury through the induction of oxidative stress and produce systemic inflammation similar to that seen in acute HE patients. In this short review article, we shortly review the most important pathological findings in animal models of acute HE following the administration of TAA.