Article
Chemistry, Analytical
Marie-Laure Custers, Yessica Wouters, Tom Jaspers, Dimitri De Bundel, Maarten Dewilde, Ann Van Eeckhaut, Ilse Smolders
Summary: The study investigates the application of receptor-mediated transcytosis for delivering biologics to the central nervous system, offering new possibilities for treating CNS disorders. By comparing two sampling techniques for the cerebral interstitial fluid, it is found that both microdialysis and open flow microperfusion are suitable for quantifying nanobodies in the CNS.
ANALYTICA CHIMICA ACTA
(2021)
Article
Pharmacology & Pharmacy
Thomas Altendorfer-Kroath, Joanna Hummer, Denise Kollmann, Beate Boulgaropoulos, Reingard Raml, Thomas Birngruber
Summary: The study aimed to quantify the therapeutic antibody ocrelizumab (OCR) in mouse brain interstitial fluid (ISF) and record its pharmacokinetic (PK) profile using cerebral open flow microperfusion (cOFM). The blood-brain barrier (BBB) integrity was also monitored using an endogenous antibody. The data obtained provide a reliable basis for assessing the PK of therapeutic antibodies in the brain, promoting their further development.
Review
Endocrinology & Metabolism
Claudia A. Smith, Keri L. H. Carpenter, Peter J. Hutchinson, Peter Smielewski, Adel Helmy
Summary: The loss of cerebral autoregulation (CA) is a common and detrimental secondary injury mechanism following acute brain injury. Neuroinflammation, particularly inflammation affecting the cerebral vasculature, could be a putative mechanism that causes CA dysfunction. This review provides an overview of CA, its impairment following brain injury, and discusses potential mechanisms and markers related to disturbance of the cerebral blood flow and autoregulation.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Review
Neurosciences
Blanca Diaz-Castro, Stefanie Robel, Anusha Mishra
Summary: Astrocyte endfeet surround the entire vascular tree in the central nervous system and play important roles in regulating the blood-brain barrier, cerebral blood flow, nutrient uptake, and waste clearance. They contain specialized organelles and proteins necessary for astrocyte-vascular interactions. Many neurological diseases are associated with abnormalities in astrocyte endfeet, including loss of protein polarization, vascular dysregulation, and disruption of the blood-brain barrier. This review provides an overview of astrocyte endfeet and highlights the need for future research to address gaps in our understanding.
ANNUAL REVIEW OF NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Gaku Yamanaka, Fuyuko Takata, Yasufumi Kataoka, Kanako Kanou, Shinichiro Morichi, Shinya Dohgu, Hisashi Kawashima
Summary: Pericytes are crucial for maintaining the integrity of the blood-brain barrier and have been implicated in neuroinflammation associated with epilepsy. Clinical and experimental studies have shown that pericytes undergo morphological changes and redistribution in response to proinflammatory cytokines, potentially contributing to epilepsy pathogenesis and BBB permeability. Furthermore, pericytes may act as sensors of the inflammatory response and have potential as a therapeutic target for seizure disorders.
Review
Immunology
Zaib A. Shaheryar, Mahtab A. Khan, Ch. Sherjeel Adnan, Awais Ali Zaidi, Daniel Hanggi, Sajjad Muhammad
Summary: Ischemic stroke is a major cause of mortality and morbidity globally, but there is currently no definitive and effective treatment. Various treatment options have been proposed, but targeting the intricate intracellular signaling pathways of the 'neuroinflammatory triangle' may be more pragmatic in limiting post-stroke damage and disabilities.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Damian M. Bailey, Anthony R. Bain, Ryan L. Hoiland, Otto F. Barak, Ivan Drvis, Christophe Hirtz, Sylvain Lehmann, Nicola Marchi, Damir Janigro, David B. MacLeod, Philip N. Ainslie, Zeljko Dujic
Summary: In this study, it was found that prolonged apnea duration during voluntary asphyxia leads to increased cerebral blood flow and blood-brain barrier permeability. The study highlights the critical role of hypoxemia and hypercapnia in BBB disruption.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Review
Pharmacology & Pharmacy
Thomas Altendorfer-Kroath, Joanna Hummer, Thomas Birngruber
Summary: The in vivo investigation of brain pharmacokinetics and pharmacodynamics (PK/PD) is crucial for drug development in neurology. However, the blood-brain barrier (BBB) can greatly reduce drug concentrations in the brain. Therefore, highly sensitive measurement methods are needed. One of these methods is cerebral open flow microperfusion (cOFM), which allows for the measurement of cerebral compound concentrations while maintaining the integrity of the BBB.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2023)
Article
Medicine, Research & Experimental
Jing Xu, Guanghui Zheng, Juntao Hu, Weiwei Ge, Jennifer L. Bradley, Joseph P. Ornato, Wanchun Tang
Summary: This study investigated the efficacy of the monoacylglycerol lipase (MAGL) inhibitor, JZL184, on post-resuscitation cerebral ischemia-reperfusion injury (IRI) and compared its effects to therapeutic hypothermia. The results showed that JZL184 had comparable neuro-protective effects to therapeutic hypothermia on global cerebral IRI in a rat model of cardiac arrest (CA).
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Engineering, Biomedical
Qianru Yang, Alberto L. Vazquez, Xinyan Tracy Cui
Summary: Advancements in in vivo imaging technologies, such as two-photon microscopy, have improved our understanding of biomaterials in the brain, but chronic studies show limitations in high-resolution imaging due to inflammatory responses caused by craniotomy and foreign biomaterial insertion. Microprisms offer a unique vertical view breaking through this imaging depth limitation, but responses to microprism implants in vivo remain unclear. Analysis of microglial/macrophage activation and morphology after microprism implantation revealed changes in cell density and processes, indicating eventual inactive phenotypes. Long-term observations using microprisms showed sustained microglial/macrophage responses to injuries, suggesting feasibility for inflammatory response characterizations at deeper depths than traditional methods.
Review
Pharmacology & Pharmacy
Ye Peng, Shifeng Chu, Yantao Yang, Zhao Zhang, Zongran Pang, Naihong Chen
Summary: Cell cultures are widely used in pharmaceutical, medical, and biological sciences. Neuronal and glial cell models are important tools for researching neurological disorders, with current studies on neuroinflammation contributing to understanding blood-brain barrier damage. Immortalized cell lines of the central nervous system are being used to study anti-inflammatory potential in neurological disorders, with 2D and 3D co-culture models being discussed for their different advantages and limitations.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
David Scieszka, Yan Jin, Shahani Noor, Ed Barr, Marcus Garcia, Jessica Begay, Guy Herbert, Russell P. Hunter, Kiran Bhaskar, Rahul Kumar, Rama Gullapalli, Alicia Bolt, Mark A. McCormick, Barry Bleske, Haiwei Gu, Matthew J. Campen
Summary: This study investigated the effects of biomass-derived smoke on neuroinflammation and metabolomics. Long-term exposure to wood smoke caused changes in neurovascular endothelial phenotypes and neuroinflammation, which gradually resolved after 28 days. Furthermore, smoke exposure also affected neurotransmitters and NAD+ metabolism.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Adchara Janyou, Aida Moohammadaree, Pichaya Jumnongprakhon, Chainarong Tocharus, Ratchanaporn Chokchaisiri, Apichart Suksamrarn, Jiraporn Tocharus
Summary: This study investigated the effects of isosakuranetin on cerebral infarction and blood brain barrier damage in a rat model of cerebral ischemia and reperfusion. The results showed that isosakuranetin reduced neurological damage, decreased infarct volume, and attenuated BBB leakage. Therefore, isosakuranetin has a protective effect against cerebral ischemia and reperfusion injury.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Clinical Neurology
Matilde Bruno, Chiara Giuseppina Bonomi, Francesco Ricci, Martina Gaia Di Donna, Nicola Biagio Mercuri, Giacomo Koch, Alessandro Martorana, Caterina Motta
Summary: This study investigated the relationship between BBB permeability and neuroinflammation in AD patients. The findings suggest that different neuroinflammatory profiles can be associated with different levels of BBB permeability in AD.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Neurosciences
Lu Cao, Yanbo Zhou, Mengguang Chen, Li Li, Wei Zhang
Summary: Pericytes are multipotent cells located on capillaries and play a crucial role in maintaining the blood-brain barrier and regulating the neurovascular system. Dysfunction of pericytes can lead to diseases such as stroke. Recent studies suggest that pericytes can be a therapeutic target for ischemic stroke.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Werner Regittnig, Mathias Tschaikner, Alexandru-Cristian Tuca, Amra Simic, Juergen Feiel, Roland Schaller-Ammann, Alexander H. Licht, Miro Jungklaus, Thomas R. Pieber
Summary: The study revealed that insulin leads to a progressive increase in the resistance of subcutaneous tissue to fluid introduction, which has significant implications for the future design of insulin pumps and infusion sets.
DIABETES OBESITY & METABOLISM
(2022)
Letter
Endocrinology & Metabolism
Thomas R. Pieber, Harpreet S. Bajaj, Simon R. Heller, Ting Jia, Kamlesh Khunti, David C. Klonoff, Steen Ladelund, Lawrence A. Leiter, Lily Wagner, Athena Philis-Tsimikas
DIABETES OBESITY & METABOLISM
(2022)
Article
Genetics & Heredity
Olivia Trummer, Ines Foessl, Natascha Schweighofer, Edi Arifi, Christoph W. Haudum, Sharmaine Reintar, Stefan Pilz, Verena Theiler-Schwetz, Christian Trummer, Andreas Zirlik, Albrecht Schmidt, Caterina Colantonio, Ewald Kolesnik, Nicolas Verheyen, Thomas R. Pieber, Barbara Obermayer-Pietsch
Summary: The aim of this study was to assess the differential expression of 9 selected miRNAs related to immunological functions between patients with Hashimoto's thyroiditis (HT) and healthy controls. The results showed that miR21-5p, miR-22-3p, miR-22-5p, miR-142-3p, miR-146a-5p, miR-301-3p, and miR-451 were significantly upregulated in HT patients and altered expressions of miR-22-5p and miR-142-3p were associated with higher levels of thyroid antibodies.
Letter
Endocrinology & Metabolism
Thomas R. Pieber, Ronnie Aronson, Mark P. Christiansen, Bruce Bode, Khaled Junaidi, Valentina Conoscenti
DIABETES OBESITY & METABOLISM
(2022)
Review
Pharmacology & Pharmacy
Felix Aberer, Thomas R. Pieber, Max L. Eckstein, Harald Sourij, Othmar Moser
Summary: This narrative review examined clinical trials investigating glucose-lowering agents as an adjunct to insulin treatment in individuals with Type 1 diabetes. The results showed that several adjunct agents demonstrated improvements in HbA1c, reductions in hypoglycemia risk, lower insulin requirements, and positive effects on cardiovascular risk factors.
Article
Biochemistry & Molecular Biology
Martina Brunner, Othmar Moser, Reingard Raml, Maximilian Haberlander, Beate Boulgaropoulos, Barbara Obermayer-Pietsch, Eva Svehlikova, Thomas R. Pieber, Harald Sourij
Summary: Methods for glucagon analysis in the past were not specific and had a narrow sensitivity range, leading to inaccurate results. Newer methods have shown that actual glucagon levels are lower than previously thought. This study compared glucagon levels in healthy individuals and diabetes patients using two different methods and found that the choice of method can significantly affect the results.
Review
Pharmacology & Pharmacy
Thomas Altendorfer-Kroath, Joanna Hummer, Thomas Birngruber
Summary: The in vivo investigation of brain pharmacokinetics and pharmacodynamics (PK/PD) is crucial for drug development in neurology. However, the blood-brain barrier (BBB) can greatly reduce drug concentrations in the brain. Therefore, highly sensitive measurement methods are needed. One of these methods is cerebral open flow microperfusion (cOFM), which allows for the measurement of cerebral compound concentrations while maintaining the integrity of the BBB.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2023)
Article
Endocrinology & Metabolism
Simon Heller, Tadej Battelino, Timothy S. Bailey, Thomas R. Pieber, Ulrike Hoevelmann, Leona Plum-Moerschel, Anita E. Melgaard, Ronnie Aronson, Linda A. DiMeglio, Thue Johansen, Thomas Danne
Summary: This study analyzed the safety and efficacy of dasiglucagon, a glucagon analogue, in treating severe hypoglycemia in patients with type 1 diabetes. The results showed that dasiglucagon had a similar safety profile as reconstituted glucagon and was more effective in glucose recovery compared to placebo.
DIABETES OBESITY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Max Schuller, Monika Oberhuber, Barbara Prietl, Elmar Zugner, Eva-Maria Prugger, Christoph Magnes, Alexander H. Kirsch, Sabine Schmaldienst, Thomas Pieber, Marianne Brodmann, Alexander R. Rosenkranz, Philipp Eller, Kathrin Eller
Summary: Coronavirus disease 2019 (COVID-19)-induced metabolic alterations can serve as prognostic biomarkers and have potential therapeutic implications. The study examined the metabolic impact of COVID-19 in hemodialysis patients and found that the effects were less significant compared to non-hemodialysis patients. Elevated kynurenine levels and lipid dysregulation were identified as potential universal biomarkers for moderate and severe COVID-19, independent of kidney function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Norbert J. Tripolt, Sebastian J. Hofer, Peter N. Pferschy, Faisal Aziz, Sylvere Durand, Fanny Aprahamian, Nitharsshini Nirmalathasan, Mara Waltenstorfer, Tobias Eisenberg, Anna M. A. Obermayer, Regina Riedl, Harald Kojzar, Othmar Moser, Caren Sourij, Heiko Bugger, Abderrahim Oulhaj, Thomas R. Pieber, Matthias Zanker, Guido Kroemer, Frank Madeo, Harald Sourij
Summary: The effects of fasting on glucose metabolism were examined in non-obese and obese participants and people with type 2 diabetes. The results showed that after 36 hours of fasting, glucose, insulin, and C-peptide levels were significantly decreased. Non-obese participants had higher glucose levels but lower insulin levels after 36 hours of fasting, while no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 hours of fasting. Metabolomics analysis revealed subtle baseline differences and attenuated metabolic response to fasting in obese participants and people with diabetes.
Article
Nutrition & Dietetics
Natascha Schweighofer, Christoph W. W. Haudum, Olivia Trummer, Alice Lind, Ewald Kolesnik, Ines Mursic, Albrecht Schmidt, Daniel Scherr, Andreas Zirlik, Thomas R. R. Pieber, Nicolas Verheyen, Barbara Obermayer-Pietsch
Summary: Sarcopenia is associated with increased risk of falls, osteoporosis, and mortality, and poses a growing problem for healthcare systems. This study finds that dp-ucMGP may be a good biomarker candidate for sarcopenia characterization, as it correlates with sarcopenia parameters such as gait speed, appendicular skeletal muscle mass, and appendicular skeletal muscle mass index.
Article
Endocrinology & Metabolism
Thomas R. Pieber, Kristine N. Arfelt, Roman Cailleteau, Marlies Hart, Soumitra Kar, Ines Mursic, Eva Svehlikova, Martina Urschitz, Hanne Haahr
Summary: This study compared the frequency and recovery of hypoglycemia after double or triple doses of once-weekly insulin icodec and once-daily insulin glargine U100. The study also compared the symptomatic and hormonal responses to hypoglycemia between the two treatments. The results showed that there was no significant difference in the risk of hypoglycemia between icodec and glargine U100, but icodec elicited slightly higher symptomatic and endocrine responses during hypoglycemia compared to glargine U100.
Article
Biochemical Research Methods
Thomas Altendorfer-Kroath, Martin Asslaber, Joanna Hummer, Beate Boulgaropoulos, Barbara Prietl, Thomas R. Pieber, Eva Bernhart, Thomas Birngruber
Summary: In this study, an atraumatic access to glioblastoma in rat brain was successfully established using cOFM method, which allows collection of reliable data and promotes cancer treatment and biomarker research.
JOURNAL OF NEUROSCIENCE METHODS
(2023)
Article
Medicine, General & Internal
Veronika Tandl, Christoph Haudum, Katharina Eberhard, Barbara Hutz, Ines Foessl, Ewald Kolesnik, Andreas Zirlik, Dirk von Lewinski, Daniel Scherr, Nicolas Verheyen, Thomas Pieber, Barbara Obermayer-Pietsch
Summary: Serum concentrations of AMH decrease with increasing BMI, possibly due to either an adverse effect of adiposity on AMH production or dilution from greater blood volume. We investigated the relationships between AMH levels and body composition parameters in adult males and found that body weight, lean mass, and body surface area were better predictors of AMH than measures of adiposity. Since both lean mass and body surface area correlate with plasma volume better than adipose tissue, we conclude that hemodilution of AMH does occur in adult males and should be considered for normalization in future studies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Thomas Altendorfer-Kroath, Joanna Hummer, Denise Kollmann, Beate Boulgaropoulos, Reingard Raml, Thomas Birngruber
Summary: The study aimed to quantify the therapeutic antibody ocrelizumab (OCR) in mouse brain interstitial fluid (ISF) and record its pharmacokinetic (PK) profile using cerebral open flow microperfusion (cOFM). The blood-brain barrier (BBB) integrity was also monitored using an endogenous antibody. The data obtained provide a reliable basis for assessing the PK of therapeutic antibodies in the brain, promoting their further development.
