Abstract:
:Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 are two crucial mediators contributing to blood-brain barrier (BBB) damage during cerebral ischemia. However, it is not known whether MMP-9 activation is involved in COX-2-mediated BBB disruption in ischemic stroke. In this study, we hypothesized that genetic deletion or pharmacological inhibition of COX-2 reduces BBB damage by reducing MMP-9 activity in a mouse model of ischemic stroke. Male COX-2 knockout (COX-2-/-) and wild-type (WT) mice were subjected to 60 min of middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Genetic deletion of COX-2 or post-ischemic treatment with CAY10404, a highly selective COX-2 inhibitor, significantly reduced BBB damage and hemorrhagic transformation, as assessed by immunoglobulin G (IgG) extravasation and brain hemoglobin (Hb) levels, respectively. Immunoblotting analysis showed that tight junction proteins (TJPs) zonula occludens (ZO)-1 and occludin as well as junctional adhesion molecule-A (JAM-A) and the basal lamina protein collagen IV were dramatically reduced in the ischemic brain. Stroke-induced loss of these BBB structural proteins was significantly attenuated in COX-2-/- mice. Similarly, stroke-induced loss of ZO-1 and occludin was significantly attenuated by CAY10404 treatment. Ischemia-induced increase in MMP-9 protein levels in the ipsilateral cerebral cortex was significantly reduced in COX-2-/- mice. Stroke induced a dramatic increase in MMP-9 enzymatic activity in the ischemic cortex, which was markedly reduced by COX-2 gene deficiency or pharmacological inhibition with CAY10404. Levels of myeloperoxidase (MPO, an indicator of neutrophil infiltration into the brain parenchyma), neutrophil elastase (NE), and lipocalin-2 (LCN2, also known as neutrophil gelatinase-associated lipocalin), measured by western blot and specific ELISA kits, respectively, were markedly increased in the ischemic brain. Increased levels of markers for neutrophil infiltration were significantly reduced in COX-2-/- mice compared with WT controls following stroke. Altogether, neurovascular protective effects of COX-2 blockade are associated with reduced BBB damage, MMP-9 expression/activity and neutrophil infiltration. Our study shows for the first time that MMP-9 is an important downstream effector contributing to COX-2-mediated neurovascular damage in ischemic stroke. Targeting the COX-2/MMP-9 pathway could represent a promising strategy to reduce neuroinflammatory events in order to preserve the BBB integrity and ameliorate ischemic stroke injury.
journal_name
Front Neuroljournal_title
Frontiers in neurologyauthors
Yang C,Yang Y,DeMars KM,Rosenberg GA,Candelario-Jalil Edoi
10.3389/fneur.2020.00887subject
Has Abstractpub_date
2020-08-20 00:00:00pages
887issn
1664-2295journal_volume
11pub_type
杂志文章abstract::We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3-5 years' duration while working on ...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2018.00351
更新日期:2018-05-16 00:00:00
abstract::Background: Magnetic resonance imaging is a key diagnostic and monitoring tool in multiple Sclerosis (MS). While the substrates of motor and neuropsychological symptoms in MS have been extensively investigated, nystagmus-associated imaging signatures are relatively under studied. Accordingly, the objective of this stu...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00691
更新日期:2018-08-23 00:00:00
abstract::Introduction: Novel therapies are needed for the treatment of motion sickness given the inadequate relief and bothersome and dangerous adverse effects of currently approved therapies. Neurokinin-1 (NK1) receptor antagonists have the potential to be effective in improving the symptoms of motion sickness, given the invo...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2020.563373
更新日期:2020-09-29 00:00:00
abstract::Hemorrhagic cerebrovascular disease in the pediatric population can have devastating and long-term effects. Progress in the fields of genetics, neuroimaging, pharmacology, and surgical techniques has led to improved diagnosis and management of pediatric cerebrovascular diseases. In this review we discuss the current e...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.01055
更新日期:2020-09-17 00:00:00
abstract::Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in pat...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2014.00047
更新日期:2014-04-09 00:00:00
abstract::Huntington's Disease (HD) is a genetic neurodegenerative disease caused by a CAG expansion in the gene encoding Huntingtin (Htt). It is characterized by chorea, cognitive, and psychiatric disorders. The most affected brain region is the striatum, and the clinical symptoms are directly correlated to the rate of striata...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2013.00127
更新日期:2013-10-23 00:00:00
abstract::Current efficacious treatments for traumatic brain injury (TBI) are lacking. Establishment of a protective gut microbiota population offers a compelling therapeutic avenue, as brain injury induces disruptions in the composition of the gut microbiota, i.e., gut dysbiosis, which has been shown to contribute to TBI-relat...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2019.00875
更新日期:2019-08-16 00:00:00
abstract:OBJECTIVE:To perform two scoping systematic reviews of the literature on cytokine measurement in: 1. cerebral microdialysis (CMD) and 2. cerebrospinal fluid (CSF) in severe traumatic brain injury (TBI) patients. METHODS:Two separate systematic reviews were conducted: one for CMD cytokines and the second for CSF cytoki...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00331
更新日期:2017-07-10 00:00:00
abstract::The development of wearable devices has increase interest in the use of ambulatory methods to detect sleep disorders more objectively than those permitted by subjective scales evaluating sleep quality, while subjects maintain their usual lifestyle. This study aims to validate an ambulatory circadian monitoring (ACM) d...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00356
更新日期:2019-04-11 00:00:00
abstract::Objective: To investigate the hemodynamic features before and after embolization of paraclinoidal aneurysms using hemodynamic numerical simulation and the influence of embolization on recurrence after embolization. Methods: From January 2016 to December 2017, we enrolled a total of 113 paraclinoidal aneurysms treated ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00429
更新日期:2019-04-25 00:00:00
abstract::Background: Chronic progressive neurological diseases like high grade glioma (HGG), Parkinson's disease (PD), and multiple sclerosis (MS) are incurable, and associated with increasing disability including cognitive impairment, and reduced life expectancy. Patients with these diseases have complex care needs. Therefore...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.01157
更新日期:2019-01-14 00:00:00
abstract::Epilepsy is associated with abnormal spatiotemporal changes in resting-state brain connectivity, but how these changes are characterized in interhemispheric coupling remains unclear. This study aimed to characterize frequency-dependent alterations in voxel-wise mirrored homotopic connectivity (VMHC) measured by restin...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00645
更新日期:2020-07-29 00:00:00
abstract::There is increasing evidence for hippocampal involvement in Amyotrophic Lateral Sclerosis (ALS). Recent neuroimaging studies have been focused on disease-related hippocampal volume alterations while changes in hippocampal shape have been investigated less frequently. Here, we aimed to characterize the patterns of hipp...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00565
更新日期:2018-07-20 00:00:00
abstract::[This corrects the article DOI: 10.3389/fneur.2020.578924.]. ...
journal_title:Frontiers in neurology
pub_type: 已发布勘误
doi:10.3389/fneur.2020.638735
更新日期:2021-01-12 00:00:00
abstract:OBJECTIVE:Our aim was to identify the role of the investigators' knowledge of the patient's history of vestibular symptoms (PVH) in the clinical evaluation of the bedside head-impulse test (bHIT). We hypothesized that this knowledge will reduce uncertainty and improve bHIT accuracy when compared to quantitative analysi...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00051
更新日期:2017-02-20 00:00:00
abstract::The combination of phasic and tonic neuromuscular processes are involved in the maintenance of normal upright posture. The latter is of particular importance in some pathologies, such as Parkinson's Disease (PD), which is known by one of its cardinal symptoms-tonic dysfunction (i.e., rigidity). Changes in tonic functi...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.01130
更新日期:2019-01-21 00:00:00
abstract::Inflammatory myositis (IM) and myasthenia gravis (MG) are both immune disorders involving muscle. The concurrent presence of both conditions in the same patient is extremely rare and the diagnosis is important and challenging. Here, we report a case of concurrent myositis and myocarditis and MG without thymoma in a 69...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2019.00770
更新日期:2019-07-16 00:00:00
abstract::The sensorimotor transformations performed by central vestibular neurons constantly adapt as the animal faces conflicting sensory information or sustains injuries. To ensure the homeostasis of vestibular-related functions, neural changes could in part rely on the regulation of 2° VN intrinsic properties. Here we revie...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00025
更新日期:2012-02-28 00:00:00
abstract::Studies suggest that microRNAs that regulate expression of matrix metalloproteinase (MMP)-9 may be involved in hemorrhagic transformation (HT) after cardioembolic stroke, so we examined whether such microRNAs could predict HT in acute cardioembolic stroke patients. Blood samples were prospectively collected from patie...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00945
更新日期:2019-09-06 00:00:00
abstract::Introduction: Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking. Patients and Methods: In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediat...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.01000
更新日期:2020-09-08 00:00:00
abstract::Background: Prolonged static whole-body roll-tilt has been shown to bias estimates of the direction of gravity when assessed by static paradigms such as the subjective visual vertical and the subjective haptic vertical. Objective: We hypothesized that these shifts are paradigm-independent and thus predicted a post-til...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.595975
更新日期:2020-10-15 00:00:00
abstract::Object: Predicting whether intramedullary slitlike cavity (SC) will worsen over time or remain stable is an outstanding clinical challenge. The aim of this study was to identify early features of SC (clinical and magnetic resonance imaging [MRI] findings). Methods: We prospectively included all patients referred to ou...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00495
更新日期:2020-06-12 00:00:00
abstract::Stroke is a leading cause of death and disability, and recombinant tissue plasminogen activator (rtPA) can significantly reduce the long-term impact of acute ischemic stroke (AIS) if given within 3 h of symptom onset. South Carolina is located in the "stroke belt" and has a high rate of stroke and stroke mortality. Ma...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00044
更新日期:2012-03-21 00:00:00
abstract::Excessive daytime sleepiness (EDS) is a prevalent sleep-related complaint across the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. However, the association between E...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01282
更新日期:2019-12-03 00:00:00
abstract::Introduction: This study was designed to evaluate risk factors and incidence of epilepsy-related injuries and accidents (ERIA) at an outpatient clinic of a German epilepsy center providing healthcare to a mixed urban and rural population of over one million inhabitants. Methods: Data acquisition was performed between ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00414
更新日期:2018-06-15 00:00:00
abstract::[This corrects the article DOI: 10.3389/fneur.2018.00662.]. ...
journal_title:Frontiers in neurology
pub_type: 杂志文章,已发布勘误
doi:10.3389/fneur.2019.00031
更新日期:2019-02-05 00:00:00
abstract::Hemiconvulsion-hemiplegia-epilepsy syndrome (HHE) is a rare outcome of prolonged hemiconvulsion that is followed by diffuse unilateral hemispheric edema, hemiplegia, and ultimately hemiatrophy of the affected hemisphere and epilepsy. Here, we describe the case of a 3-year-old male with a 1;3 translocation leading to a...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2016.00067
更新日期:2016-05-04 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative condition, most widely characterized by the selective vulnerability of motor neurons and the poor life expectancy of afflicted patients. Limited disease-modifying therapies currently exist, which only further attests to the substantial heterogeneity...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.00377
更新日期:2020-05-27 00:00:00
abstract::Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which is independently correlated with negative clinical outcome. The identification of specific biomarkers could help to increase the sensitivity of PSD diagnosis and elucidate its pathophysiological mechanisms. The aim of current st...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2018.00577
更新日期:2018-07-16 00:00:00
abstract::The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA t...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2014.00242
更新日期:2014-12-15 00:00:00