scholarly journals The Role of Urocortins in Intracerebral Hemorrhage

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 96 ◽  
Author(s):  
Ker Woon Choy ◽  
Andy Po-Yi Tsai ◽  
Peter Bor-Chian Lin ◽  
Meng-Yu Wu ◽  
Chihyi Lee ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Regions ◽  
Brain Parenchyma ◽  
Protective Mechanisms ◽  
Neuroprotective Effects ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
G Protein Coupled ◽  
The Brain

Intracerebral hemorrhage (ICH) causes an accumulation of blood in the brain parenchyma that disrupts the normal neurological function of the brain. Despite extensive clinical trials, no medical or surgical therapy has shown to be effective in managing ICH, resulting in a poor prognosis for the patients. Urocortin (UCN) is a 40-amino-acid endogenous neuropeptide that belongs to the corticotropin-releasing hormone (CRH) family. The effect of UCN is activated by binding to two G-protein coupled receptors, CRH-R1 and CRH-R2, which are expressed in brain neurons and glial cells in various brain regions. Current research has shown that UCN exerts neuroprotective effects in ICH models via anti-inflammatory effects, which generally reduced brain edema and reduced blood-brain barrier disruption. These effects gradually help in the improvement of the neurological outcome, and thus, UCN may be a potential therapeutic target in the treatment of ICH. This review summarizes the data published to date on the role of UCN in ICH and the possible protective mechanisms underlined.

scholarly journals Protective Role of Early Aquaporin 4 Induction against Postischemic Edema Formation

2008 ◽  
Vol 29 (2) ◽  
pp. 423-433 ◽  
Author(s):  
Lorenz Hirt ◽  
Béatrice Ternon ◽  
Melanie Price ◽  
Nabil Mastour ◽  
Jean-François Brunet ◽  
...  
Keyword(s):  
Water Channel ◽  
Protective Role ◽  
Aquaporin 4 ◽  
Late Time ◽  
Protective Mechanisms ◽  
Edema Formation ◽  
Aqp4 Expression ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption

Aquaporin 4 (AQP4) is a water channel involved in water movements across the cell membrane and is spatially organized on the cell surface in orthogonal array particles (OAPs). Its role in edema formation or resolution after stroke onset has been studied mainly at late time points. We have shown recently that its expression is rapidly induced after ischemia coinciding in time with an early swelling of the ischemic hemisphere. There are two isoforms of AQP4: AQP4-M1 and AQP4-M23. The ratio of these isoforms influences the size of the OAPs but the functional impact is not known. The role of the early induction of AQP4 is not yet known. Thrombin preconditioning in mice provides a useful model to study endogenous protective mechanisms. Using this model, we provide evidence for the first time that the early induction of AQP4 may contribute to limit the formation of edema and that the AQP4-M1 isoform is predominantly induced in the ischemic tissue at this time point. Although it prevents edema formation, the early induction of the AQP4 expression does not prevent the blood—brain barrier disruption, suggesting an effect limited to the prevention of edema formation possibly by removing of water from the tissue.

scholarly journals 7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph Bryant ◽  
Sanketh Andhavarapu ◽  
Christopher Bever ◽  
Poornachander Guda ◽  
Akhil Katuri ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Brain Regions ◽  
Future Research ◽  
Neurocognitive Disorder ◽  
Neuroprotective Effects ◽  
Antiviral Therapies ◽  
Combined Antiretroviral Therapy ◽  
Hiv Associated Neurocognitive Disorder ◽  
The Brain

AbstractThe combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In PWH, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile. Therefore, we investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. In these brain regions, we observed astrogliosis, increased expression of chemokine HIV-1 coreceptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Moreover, our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB–Akt–NFkB signaling pathway in mediating these pathological hallmarks. These findings guide future research as DHF shows promise as a TrkB agonist treatment for HAND patients in adjunction to the current antiviral therapies.

Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents

2021 ◽  
Vol 118 (42) ◽  
pp. e2102340118
Author(s):  
He Wei ◽  
Agata Wiśniowska ◽  
Jingxuan Fan ◽  
Peter Harvey ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Contrast Agents ◽  
Brain Parenchyma ◽  
Mri Contrast Agents ◽  
Imaging Agents ◽  
Mri Contrast ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
The Brain ◽  
Superparamagnetic Properties

Magnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T1-weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents. We show that SNIOs permeate biological tissue effectively following injection into brain parenchyma or cerebrospinal fluid. We also demonstrate that SNIOs readily enter the brain following ultrasound-induced blood–brain barrier disruption, emulating the performance of a gadolinium agent and providing a basis for future biomedical applications. These results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.

scholarly journals Impact of Drug Size on Brain Tumor and Brain Parenchyma Delivery after a Blood–Brain Barrier Disruption

2014 ◽  
Vol 34 (5) ◽  
pp. 820-826 ◽  
Author(s):  
Marie Blanchette ◽  
Luc Tremblay ◽  
Martin Lepage ◽  
David Fortin
Keyword(s):  
Blood Brain Barrier ◽  
Time Window ◽  
Molecular Size ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Cas A ◽  
The Brain

Drug delivery to the brain is influenced by the blood–brain barrier (BBB) and blood–tumor barrier (BTB) to an extent that is still debated in neuro-oncology. In this paper, we studied the delivery across the BTB and the BBB of compounds with different molecular sizes in normal and glioma-bearing rats. Studies were performed at baseline as well as after an osmotic BBB disruption (BBBD) using dynamic contrast-enhanced magnetic resonance imaging and two T1, contrast agents (CAs), Magnevist (743 Da) and Gadomer (17,000 Da). More specifically, we determined the time window for the BBB permeability, the distribution and we calculated the brain exposure to the CAs. A different pattern of accumulation and distribution at baseline as well as after a BBBD procedure was observed for both agents, which is consistent with their different molecular size and weight. Baseline tumor exposure was threefold higher for Magnevist compared with Gadomer, whereas postBBBD tumor exposure was twofold higher for Magnevist. Our study clearly showed that the time window and the extent of delivery across the intact, as well as permeabilized BTB and BBB are influenced by drug size.

The treatment of brain metastasis from breast cancer, role of blood-brain barrier disruption and early experience with trastuzumab

Therapy ◽  
2006 ◽  
Vol 3 (1) ◽  
pp. 97-112 ◽  
Author(s):  
Rose Marie Tyson ◽  
Dale F Kraemer ◽  
Matthew A Hunt ◽  
Leslie L Muldoon ◽  
Peter Orbay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Blood Brain Barrier ◽  
Early Experience ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

scholarly journals The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1475
Author(s):  
Waldemar Kryszkowski ◽  
Tomasz Boczek
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Glutamate Release ◽  
Molecular Targets ◽  
Brain Regions ◽  
Psychotic Symptoms ◽  
Unknown Etiology ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

Schizophrenia is a severe neuropsychiatric disease with an unknown etiology. The research into the neurobiology of this disease led to several models aimed at explaining the link between perturbations in brain function and the manifestation of psychotic symptoms. The glutamatergic hypothesis postulates that disrupted glutamate neurotransmission may mediate cognitive and psychosocial impairments by affecting the connections between the cortex and the thalamus. In this regard, the greatest attention has been given to ionotropic NMDA receptor hypofunction. However, converging data indicates metabotropic glutamate receptors as crucial for cognitive and psychomotor function. The distribution of these receptors in the brain regions related to schizophrenia and their regulatory role in glutamate release make them promising molecular targets for novel antipsychotics. This article reviews the progress in the research on the role of metabotropic glutamate receptors in schizophrenia etiopathology.

Matrix metalloproteinase—9 concentration after spontaneous intracerebral hemorrhage

2003 ◽  
Vol 99 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Sònia Abilleira ◽  
Joan Montaner ◽  
Carlos A. Molina ◽  
Jasone Monasterio ◽  
José Castillo ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neurological Diseases ◽  
Neurological Status ◽  
Acute Stage ◽  
Ct Scans ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Fine Print

Object. Matrix metalloproteinases (MMPs) are overexpressed in the presence of some neurological diseases in which blood—brain barrier disruption exists. The authors investigated the MMP-9 concentration in patients after acute intracerebral hemorrhage (ICH) and its relation to perihematomal edema (PHE). Methods. Concentrations of MMP-9 and related proteins were determined in plasma by performing an enzyme-linked immunosorbent assay of samples drawn after hospital admission (< 24 hours after stroke) from 57 patients with ICH. The diagnosis of ICH was made on the basis of findings on computerized tomography (CT) scans. The volumes of ICH and PHE were measured on baseline and follow-up CT scans at the same time that the patient's neurological status was assessed using the Canadian Stroke Scale and the Glasgow Coma Scale. Increased expression of MMP-9 was found among patients with ICH. In cases of deep ICH, MMP-9 was significantly associated with PHE volume (r = 0.53; p = 0.01) and neurological worsening (237.4 compared with 111.3 ng/ml MMP-9; p = 0.04). A logistic regression model focusing on the study of absolute PHE volume showed ICH volume as an independent predictor (odds ratio [OR] 3.37; 95% confidence interval [CI] 1.1–10.3; p = 0.03). A second analysis of relative PHE volume (absolute PHE volume/ICH volume) in patients with deep ICH demonstrated that the only factor related to it was MMP-9 concentration (OR 11.6; 95% CI 1.5–89.1; p = 0.018). Conclusions. Expression of MMP-9 is raised after acute spontaneous ICH. Among patients with deep ICH this increase is associated with PHE and the development of neurological worsening within the acute stage.

scholarly journals PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

Intracerebral Hemorrhage and Diabetes Mellitus: Blood-Brain Barrier Disruption, Pathophysiology, and Cognitive Impairments

2021 ◽  
Vol 20 ◽  
Author(s):  
Ghaith A. Bahadar ◽  
Zahoor A Shah
Keyword(s):  
Diabetes Mellitus ◽  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Comorbid Condition ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
The Impact

: There is a surge in diabetes incidence with an estimated 463 million individuals been diagnosed worldwide. Diabetes Mellitus (DM) is a major stroke-related comorbid condition that increases the susceptibility of disabling post-stroke outcomes. Although less common, intracerebral hemorrhage (ICH) is the most dramatic subtype of stroke that is associated with higher mortality, particularly in DM population. Previous studies have focused mainly on the impact of DM on ischemic stroke. Few studies have focused on impact of DM on ICH and discussed the blood-brain barrier disruption, brain edema, and hematoma formation. However, more recently, investigating the role of oxidative damage and reactive oxygen species (ROS) production in preclinical studies involving DM-ICH animal models has gained attention. But, little is known about the correlation between neuroinflammatory processes, glial cells activation, and peripheral immune cell invasion with DM-ICH injury. DM and ICH patients experience impaired abilities in multiple cognitive domains by relatively comparable mechanisms, which could get exacerbated in the setting of comorbidities. In this review, we discuss both the pathology of DM as a comorbid condition for ICH and the potential molecular therapeutic targets for the clinical management of the ICH and its recovery.

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