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Frontiers in Aging Neuroscience 2020Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in ,... (Review)
Review
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in , is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. MRI imaging shows cerebral white matter (WM) hyperintensity, particularly in the external capsule and temporal pole. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL. On the other hand, atypical mutations including cysteine sparing mutation, null mutation, homozygous mutation, and other associate genes are also reported. From the viewpoint of gain of function apart from Notch signaling or loss of function of Notch signaling, we review the research article about CADASIL and summarized the pathogenesis of small vessel, stroke, and dementia in this disease.
PubMed: 32457593
DOI: 10.3389/fnagi.2020.00091 -
Stroke Jun 2023Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the...
BACKGROUND
Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes.
METHODS
We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes.
RESULTS
Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all <0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all <0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all <0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum.
CONCLUSIONS
ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.
Topics: Humans; Retrospective Studies; Cerebral Hemorrhage; Stroke; Globus Pallidus; Hematoma
PubMed: 37216445
DOI: 10.1161/STROKEAHA.122.041246 -
EClinicalMedicine Aug 2020Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural...
BACKGROUND
Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.
METHODS
In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.
FINDINGS
In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss ( value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss ( value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level ( value <0.05).
INTERPRETATION
Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.
FUNDING
Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.
PubMed: 32838240
DOI: 10.1016/j.eclinm.2020.100484 -
Journal of Neuroinflammation Aug 2021Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular...
BACKGROUND
Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na/H exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling. In this study, we examined the role of NHE1 protein in astrogliosis, white matter demyelination, and cognitive function in a murine CCH model with bilateral carotid artery stenosis (BCAS).
METHODS
Sham, BCAS, or BCAS mice receiving vehicle or a selective NHE1 inhibitor HOE642 were monitored for changes of the regional cerebral blood flow and behavioral performance for 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury and demyelination. Astrogliosis and demyelination were further examined by immunofluorescence staining. Astrocytic transcriptional profiles were analyzed with bulk RNA-sequencing and RT-qPCR.
RESULTS
Chronic cerebral blood flow reduction and spatial working memory deficits were detected in the BCAS mice, along with significantly reduced mean fractional anisotropy (FA) values in the corpus callosum, external capsule, and hippocampus in MRI DTI analysis. Compared with the sham control mice, the BCAS mice displayed demyelination and axonal damage and increased GFAP astrocytes and Iba1 microglia. Pharmacological inhibition of NHE1 protein with its inhibitor HOE642 prevented the BCAS-induced gliosis, damage of white matter tracts and hippocampus, and significantly improved cognitive performance. Transcriptome and immunostaining analysis further revealed that NHE1 inhibition specifically attenuated pro-inflammatory pathways and NADPH oxidase activation.
CONCLUSION
Our study demonstrates that NHE1 protein is involved in astrogliosis with pro-inflammatory transformation induced by CCH, and its blockade has potentials for reducing astrogliosis, demyelination, and cognitive impairment.
Topics: Animals; Astrocytes; Carotid Stenosis; Cerebrovascular Circulation; Cognition; Cognitive Dysfunction; Gliosis; Guanidines; Inflammation; Mice; Microglia; Sodium-Hydrogen Exchanger 1; Sulfones; White Matter
PubMed: 34454529
DOI: 10.1186/s12974-021-02234-8 -
BMC Medicine Jul 2023Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal...
BACKGROUND
Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain.
METHODS
We performed two-sample bidirectional Mendelian randomization (MR) analyses to explore the causal associations between IDPs and stroke. Summary data of 587 brain IDPs (up to 33,224 individuals) from the UK Biobank and five stroke types (sample size range from 301,663 to 446,696, case number range from 5,386 to 40,585) from the MEGASTROKE consortium were used.
RESULTS
Forward MR indicated 14 IDPs belong to projection fibers or association fibers were associated with stroke. For example, higher genetically determined mean diffusivity (MD) in the right external capsule was causally associated with an increased risk of small vessel stroke (IVW OR = 2.76, 95% CI 2.07 to 3.68, P = 5.87 × 10). Reverse MR indicated that genetically determined higher risk of any ischemic stroke was associated with increased isotropic or free water volume fraction (ISOVF) in body of corpus callosum (IVW β = 0.23, 95% CI 0.14 to 0.33, P = 3.22 × 10). This IDP is a commissural fiber and it is not included in the IDPs identified by forward MR.
CONCLUSIONS
We identified 14 IDPs with statistically significant evidence of causal effects on stroke or stroke subtypes. We also identified potential causal effects of stroke on one IDP of commissural fiber. These findings might guide further work toward identifying preventative strategies at the brain imaging levels.
Topics: Humans; Mendelian Randomization Analysis; Stroke; Brain; Phenotype; Neuroimaging; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37491271
DOI: 10.1186/s12916-023-02982-9 -
Neurobiology of Disease Jan 2022Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be...
Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE.
Topics: Adult; Animals; Child, Preschool; Diffusion Tensor Imaging; Epilepsy, Temporal Lobe; Humans; Myelin Sheath; Rats; Status Epilepticus; White Matter
PubMed: 34838665
DOI: 10.1016/j.nbd.2021.105566 -
Micromachines Nov 2022This paper presents a novel tattooing capsule endoscope (TCE) for delivering a certain amount of ink to the submucosal layer of digestive tract organs. A dual-function...
This paper presents a novel tattooing capsule endoscope (TCE) for delivering a certain amount of ink to the submucosal layer of digestive tract organs. A dual-function permanent magnet is used for locomotion and injection activation. The developed capsule endoscope can move actively in 5 DOF due to the interaction between the permanent magnet and a controllable external magnetic field produced by an electromagnet actuation system. In addition, the permanent magnet is involved in a specially designed mechanism to activate a process that creates a squeezing motion to eject the liquid from the storage room to the target. The dimension of the prototype is 12.5 mm in diameter and 34.6 mm in length. The proposed TCE is tested ex vivo using a fresh porcine small-intestine segment. We were able to direct the TCE to the target and deliver the tattoo agent into the tissue. The proposed mechanism can be used for drug delivery or lesion tattooing, as well as to accelerate the realization of the functional capsule endoscope in practice.
PubMed: 36557410
DOI: 10.3390/mi13122111 -
Clinics and Research in Hepatology and... Mar 2022Video capsule can illuminate the entire gastrointestinal mucosa. Upper gastrointestinal capsule endoscopy (UGICE) has the potential to survey for oesophageal, gastric... (Review)
Review
BACKGROUND
Video capsule can illuminate the entire gastrointestinal mucosa. Upper gastrointestinal capsule endoscopy (UGICE) has the potential to survey for oesophageal, gastric and duodenal pathology and determine whether biopsy or intervention is indicated.
AIMS
This review traces the evolution of foregut video capsule endoscopy.
METHODS
A broad literature research was performed independently by two investigators. Extracted articles were organized and evaluated to interpret all current data.
RESULTS
In contrast to small bowel capsule, UGICE required sequential innovations to deal with rapid oesophageal transit, the irregular shape of the stomach and unpredictable gastric peristalsis. Oesophageal capsule endoscopy required the development of a two-camera device operating at a high frame rate, and postural change was developed to improve image capture, especially at the level of the Z-line, thus providing good imaging of Barrett's oesophagus, erosive oesophagitis and oesophageal varices, with optimal patients' tolerance. UGICE in patients presenting to the emergency room with acute bleeding has demonstrated accuracy when deciding on the need for emergency intervention. The latest development of a high frame rate UGICE, designed to image the oesophagus, stomach and duodenum has overtaken dedicated oesophageal capsule development. Capsule control is possible by exposing a magnetised capsule to an external magnetic field, and early reports indicate high accuracy in the oesophagus and stomach with high levels of patient acceptability. There is little information on cost-benefit.
CONCLUSIONS
Capsule endoscopy offers gastroenterologists a new device to investigate the upper gastrointestinal tract with promising future potential.
Topics: Barrett Esophagus; Capsule Endoscopy; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Humans
PubMed: 34500118
DOI: 10.1016/j.clinre.2021.101798 -
EFORT Open Reviews Jul 2021The purpose of this systematic literature review is to analyse the role of the iliofemoral ligament (ILFL) as a hip joint stabilizer in the current literature.A total of... (Review)
Review
The purpose of this systematic literature review is to analyse the role of the iliofemoral ligament (ILFL) as a hip joint stabilizer in the current literature.A total of 26 articles were included in the review. The ILFL is the largest hip ligament consisting of two distinct arms and is highly variable, both in its location and overall size, and plays a primary role in hip stability; in the case of hip dislocation, the iliofemoral ligament tear does not heal, resulting in a persistent anterior capsule defect. Clinically, the ILFL is felt to limit external rotation in flexion and both internal and external rotation in extension.The abduction-hyperextension-external rotation (AB-HEER) test is overall the most accurate test to detect ILFL lesions. Injuries of the ILFL could be iatrogenic or a consequence of traumatic hip instability, and can be accurately studied with magnetic resonance imaging. Different arthroscopic and open techniques have been described in order to preserve the ILFL during surgery and, in case of lesions, several procedures with good to excellent results have been reported in the existing literature.The current systematic review, focusing only on the ILFL of the hip, summarizes the existing knowledge on anatomy, imaging and function and contributes to the further understanding of the ILFL, confirming its key role in anterior hip stability. Future studies will have to develop clinical tests to evaluate the functionality and stability of the ILFL. Cite this article: 2021;6:545-555. DOI: 10.1302/2058-5241.6.200112.
PubMed: 34377546
DOI: 10.1302/2058-5241.6.200112 -
Romanian Journal of Morphology and... 2022The article is a review of the latest meta-analyses regarding the genetic spectrum in schizophrenia, discussing the risks given by the disrupted-in-schizophrenia 1... (Review)
Review
The article is a review of the latest meta-analyses regarding the genetic spectrum in schizophrenia, discussing the risks given by the disrupted-in-schizophrenia 1 (DISC1), catechol-O-methyltransferase (COMT), monoamine oxidases-A∕B (MAO-A∕B), glutamic acid decarboxylase 67 (GAD67) and neuregulin 1 (NRG1) genes, and dysbindin-1 protein. The DISC1 polymorphism significantly increases the risk of schizophrenia, as well injuries from the prefrontal cortex that affect connectivity. NRG1 is one of the most important proteins involved. Its polymorphism is associated with the reduction of areas in the corpus callosum, right uncinate, inferior lateral fronto-occipital fascicle, right external capsule, fornix, right optic tract, gyrus. NRG1 and the ErbB4 receptor (tyrosine kinase receptor) are closely related to the N-methyl-D-aspartate receptor (NMDAR) (glutamate receptor). COMT is located on chromosome 22 and together with interleukin-10 (IL-10) have an anti-inflammatory and immunosuppressive function that influences the dopaminergic system. MAO gene methylation has been associated with mental disorders. MAO-A is a risk gene in the onset of schizophrenia, more precisely a certain type of single-nucleotide polymorphism (SNP), at the gene level, is associated with schizophrenia. In schizophrenia, we find deficits of the γ-aminobutyric acid (GABA)ergic neurotransmitter, the dysfunctions being found predominantly at the level of the substantia nigra. In schizophrenia, missing an allele at GAD67, caused by a SNP, has been correlated with decreases in parvalbumin (PV), somatostatin receptor (SSR), and GAD ribonucleic acid (RNA). Resulting in the inability to mature PV and SSR neurons, which has been associated with hyperactivity.
Topics: Humans; Schizophrenia; Catechol O-Methyltransferase; Receptors, N-Methyl-D-Aspartate; Polymorphism, Single Nucleotide; Monoamine Oxidase
PubMed: 36374137
DOI: 10.47162/RJME.63.2.03