Article
Neurosciences
Willian Link Papalia, Alexandre Seixas Nascimento, Gokul Krishnan, Nubia Broetto, Ana Flavia Furian, Mauro Schneider Oliveira, Luiz Fernando Freire Royes, Michele Rechia Fighera
Summary: Understanding neurovascular dysregulation after TBI is crucial for establishing scientific-based rehabilitative strategies, with physical exercise potentially playing a significant role. However, there are caveats to consider when interpreting the effect of physical exercise on neurovascular dysregulation after TBI.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Nathan A. Shlobin, Meirav Har-Even, Ze'ev Itsekson-Hayosh, Sagi Harnof, Chaim G. Pick
Summary: Thrombin is a serine protease involved in coagulation, inflammation, cell protection, and apoptosis with both neuroprotective and pathological effects in the brain. Further research is needed to fully understand its role in normal and pathological processes in the central nervous system.
Article
Pharmacology & Pharmacy
Shi-Jye Chu, Shih-En Tang, Hsin-Ping Pao, Shu-Yu Wu, Wen- Liao
Summary: This study demonstrates that the PAR-1 antagonist SCH530348 exerts protective effects by blocking PAR-1 expression and modulating the downstream PI3K, NF-kappa B, and MAPK pathways, reducing IR-induced acute lung injury. These findings suggest that PAR-1 antagonist could be a potential therapeutic candidate for lung protection following IR injury.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Elena Pompili, Valerio De Franchis, Claudia Giampietri, Stefano Leone, Elena De Santis, Francesco Fornai, Lorenzo Fumagalli, Cinzia Fabrizi
Summary: Schwann cells play a crucial role in peripheral nerve regeneration by promptly activating, dedifferentiating, and assisting axon regrowth after nerve injury. PAR1, a thrombin receptor present on Schwann cell plasma membrane, is emerging as a possible regulator of Schwann cells' pro-regenerative capacity. This review summarizes recent literature on the contribution of PAR1 and PAR1-activating proteases in regulating peripheral nerve regeneration.
Article
Hematology
Sujuan Li, Weili Wang, Lisha Lin, Lian Yang, Ying Cai, Xingzhi Yang, Taocui Zhang, Chuang Xiao, Hui Yan, Na Gao, Jinhua Zhao
Summary: An oligosaccharide HS-11, derived from sea cucumber Holothuria fuscopunctata, inhibits thrombin-mediated platelet activation and aggregation by directly binding to thrombin exosite II, demonstrating its antiplatelet and antithrombotic activity.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sukanya Tripathy, Bader O. Almutairi, Sanjay Singh, Atul Rawat, Durgesh Dubey, Monisha Banerjee, Dinesh R. Modi, Anand Prakash
Summary: Thrombin-activated receptor-1 (PAR1) plays a crucial role in tumor angiogenesis, cell proliferation, and invasion. The present study investigated the expression of PAR1 in human glioma cell lines D54 and U87, as well as its downstream signaling pathway. The results showed that PAR1 was highly expressed in D54 cells compared to U87 cells. Activation of PAR1 led to increased ERK1/2 activity and enhanced migration and invasion. The antagonist SCH79797 significantly inhibited the migration and invasion of the glioma cell lines. Moreover, PAR1 activation affected intracellular Ca+2 concentration ([Ca+2]i). Thrombin and TFLLR induced an increase in [Ca+2]i, which was suppressed by the PAR1 inhibitor SCH79797. The study suggests that PAR1 signaling contributes to glioma progression and may serve as a potential therapeutic target for glioma prevention.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Mohd Aslam Saifi, Shivaraju Annaldas, Chandraiah Godugu
Summary: The study revealed the therapeutic effect of a direct thrombin inhibitor on tubulointerstitial fibrosis in chronic kidney disease by improving kidney injury and fibrosis through inhibition of thrombin-activated PAR-1 expression.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Jean-Paul Motta, Simone Palese, Carmine Giorgio, Kevin Chapman, Alexandre Denadai-Souza, Perrine Rousset, David Sagnat, Laura Guiraud, Anissa Edir, Carine Seguy, Laurent Alric, Delphine Bonnet, Barbara Bournet, Louis Buscail, Cyrielle Gilletta, Andre G. Buret, John L. Wallace, Morley D. Hollenberg, Eric Oswald, Elisabetta Barocelli, Sylvie Le Grand, Bruno Le Grand, Celine Deraison, Nathalie Vergnolle
Summary: Elevated thrombin activity in the colon of Crohn's disease patients may lead to tissue damage and inflammation. Experimental evidence suggests that colonic thrombin and protease-activated receptor-1 could be potential mechanisms involved in mucosal damage and loss of function.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Engineering, Chemical
Mira Zaranek, Rooshan Arshad, Kevin Zheng, Carolyn A. Harris
Summary: The breakdown of the ventricular zone with the presence of blood in cerebrospinal fluid has been shown to increase shunt catheter obstruction in the treatment of hydrocephalus. Through an in vitro model, it was found that exposure of astrocytes to blood can increase cell attachment on shunt catheters. Additionally, analysis of glial fibrillary acidic protein expression showed a similar trend.
Article
Biochemistry & Molecular Biology
Shi Yi Chia, Boon-Keat Khor, Yi Juin Tay, Kok Fui Liew, Chong-Yew Lee
Summary: Sulfuretin, a naturally occurring aurone, has been found to inhibit macrophage and microglia activation. In this study, a series of aurones were synthesized to improve their activity in targeting brain microglia and overcoming the blood-brain barrier. Evaluation of these aurones showed that some compounds were able to significantly reduce nitric oxide secretion in stimulated microglia. The most potent inhibitors had bulky, planar moieties and a pendant piperidine, and they inhibited microglial polarization towards the M1 state. Compound 2a showed high blood-brain barrier permeability and could potentially be used as a lead compound in the development of aurones as microglia inhibitors.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shani Berkowitz, Shany Guly Gofrit, Shay Anat Aharoni, Valery Golderman, Lamis Qassim, Zehavit Goldberg, Amir Dori, Nicola Maggio, Joab Chapman, Efrat Shavit-Stein
Summary: The study found that there is an interaction between neuroinflammation and coagulation, and enoxaparin can protect against inflammation induced by LPS, reducing neuronal damage. The findings may provide a new pharmacological mechanism for intervening in neuroinflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Alvaro Yogi, Greg Hussack, Henk van Faassen, Arsalan S. Haqqani, Christie E. Delaney, Eric Brunette, Jagdeep K. Sandhu, Melissa Hewitt, Traian Sulea, Kristin Kemmerich, Danica B. Stanimirovic
Summary: The blood-brain barrier (BBB) limits the delivery of drugs and therapeutic antibodies to the central nervous system (CNS). This study investigates receptor-mediated transcytosis (RMT) as a means to increase drug delivery to the brain. IGF1R5, a ligand that triggers RMT, is shown to be able to cross the BBB and deliver cargo molecules. This proof-of-concept study demonstrates the potential of appropriate antibodies as RMT carriers for CNS therapeutic applications.
Article
Gastroenterology & Hepatology
Jean-Paul Motta, Celine Deraison, Sylvie Le Grand, Bruno Le Grand, Nathalie Vergnolle
Summary: A new paradigm has been proposed for the treatment of inflammatory bowel diseases, focusing on tissue repair and mucosal healing in addition to resolving symptoms and inflammation. The PAR-1 antagonist has shown potential benefits in promoting mucosal repair in Crohn's disease patients, suggesting a new indication for IBD treatment.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Wael Alata, Alvaro Yogi, Eric Brunette, Christie E. Delaney, Henk van Faassen, Greg Hussack, Umar Iqbal, Kristin Kemmerich, Arsalan S. Haqqani, Maria J. Moreno, Danica B. Stanimirovic
Summary: The study demonstrates the development of technologies targeting the blood-brain barrier to allow drugs to enter the brain. Through in vitro and in vivo experiments, the researchers showed the effectiveness of these technologies and their potential in pain treatment.
Article
Environmental Sciences
Ai Mai, Shu-Wen Ye, Jia-Yu Tu, Jun Gao, Zhan-Fang Kang, Qian-Ming Yao, Wei-Jen Ting
Summary: This study demonstrates that thymoquinone (TQ) can effectively cross the blood-brain barrier and has therapeutic potential for the treatment of glioblastoma, especially when used in combination with temozolomide (TMZ).
ENVIRONMENTAL TOXICOLOGY
(2023)
Editorial Material
Clinical Neurology
Fenghui Ye, Yingfeng Wan, Sravanthi Koduri, Katherine G. Holste, Richard F. Keep, Ya Hua, Guohua Xi
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Clinical Neurology
Chaoyi Bian, Yingfeng Wan, Sravanthi Koduri, Ya Hua, Richard F. Keep, Guohua Xi
Summary: This study found that intraventricular iron injection in rats led to hydrocephalus and increased stromal macrophage number. Treatment with minocycline or clodronate liposomes improved iron-induced hydrocephalus and reduced the increase in stromal macrophages.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Clinical Neurology
Xiaoke Hao, Zongwei Zeng, Liang Liang, Zhou Feng, Wu Li, Binyuan Xiong, Peiwen Guo, Qiang Zhang, Yujie Chen, Hua Feng, Zhi Chen
Summary: This study found that neutrophil extracellular traps (NETs) play an important role in the formation of microthrombi after subarachnoid hemorrhage (SAH). Depletion of neutrophils and DNase I treatment significantly reduced the formation of NETs and microthrombi, and improved neurological deficits, brain edema, BBB disruption, and neuronal injury after SAH induction.
TRANSLATIONAL STROKE RESEARCH
(2023)
Editorial Material
Clinical Neurology
Jiru Zhou, Peiwen Guo, Xiaoke Hao, Xiaochuan Sun, Hua Feng, Zhi Chen
Summary: Recent studies have confirmed the close association of NETs with vascular injury, neuroinflammation, and microthrombosis. NETs may serve as a new therapeutic target after subarachnoid hemorrhage, but their mechanisms and interventions need further investigation.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Neurosciences
Yingfeng Wan, Katherine G. Holste, Ya Hua, Richard F. Keep, Guohua Xi
Summary: Intracerebral hemorrhage (ICH) is responsible for 10% of strokes in the USA, resulting in significant disability and mortality. It causes primary brain injury due to mechanical disruption and secondary injury through the release of clot-derived factors. ICH leads to brain edema and increased intracranial pressure, affecting patient prognosis. Currently, effective treatment methods for reducing perihematomal cerebral edema and intracranial pressure are limited. This review explores the mechanisms of edema formation, the influence of sex and age, and the progress in pharmacotherapy for ICH.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Endocrinology & Metabolism
Fenghui Ye, Jinting Yang, Katherine G. Holste, Sravanthi Koduri, Ya Hua, Richard F. Keep, Hugh J. L. Garton, Guohua Xi
Summary: Both monocyte-derived macrophages (MDMs) and brain resident microglia contribute to hematoma resolution after intracerebral hemorrhage (ICH). In this study, transgenic mice with enhanced green fluorescent protein (EGFP) labeled microglia were used to observe changes in MDMs and microglia after ICH. The results showed that MDMs entered the brain and formed a peri-hematoma cell layer by day 3 after ICH, and CD47 blocking antibody increased the number of MDMs around and inside the hematoma. These findings suggest that MDMs play an important role in phagocytosis after ICH and modulation of MDMs could be a potential therapeutic target.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Editorial Material
Neurosciences
Yejie Shi, Richard F. Keep
NEUROBIOLOGY OF DISEASE
(2023)
Editorial Material
Neurosciences
Richard F. Keep, Lester R. Drewes
FLUIDS AND BARRIERS OF THE CNS
(2023)
Editorial Material
Neurosciences
Richard F. Keep, Hazel C. Jones, Mark G. Hamilton, Lester R. Drewes
Summary: The aim of this editorial is to highlight the advancements in brain barrier and brain fluid research in 2022. It encompasses studies on blood-brain, blood-retina, and blood-CSF barriers (choroid plexus and meninges), as well as the signaling within the neurovascular unit and elements of the brain fluid systems. Furthermore, it discusses the impact of brain barriers and brain fluid systems on CNS diseases, their role in disease progression, and the progress being made in treating such diseases.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Neurosciences
Chelsea M. Phillips, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: This study examined the epigenetic and transcriptional profile of cerebral microvessels after stroke, revealing the role of DNA methylation in regulating blood-brain barrier (BBB) repair.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Editorial Material
Neurosciences
Richard F. Keep, Hazel C. Jones, Lester R. Drewes
FLUIDS AND BARRIERS OF THE CNS
(2023)
Review
Clinical Neurology
Fenghui Ye, Richard F. Keep, Ya Hua, Hugh J. L. Garton, Guohua Xi
Summary: This article discusses the role of the glymphatic system in posthemorrhagic brain injury, especially posthemorrhagic hydrocephalus.
Article
Neurosciences
Jianming Xiang, Ya Hua, Guohua Xi, Richard F. Keep
Summary: This review evaluates the movement of fluid from blood to cerebrospinal fluid (CSF) and discusses the impact of ion transport in the choroid plexus (CP) epithelium and cerebral vasculature on fluid flow. It also addresses the potential targets for modulating CP fluid secretion, NKCC1 and TRPV4. Furthermore, it highlights the dynamic changes in fluid secretion and their role in the controversies over the CP's involvement in brain fluid secretion.
NEUROBIOLOGY OF DISEASE
(2023)
Editorial Material
Clinical Neurology
Momodou G. Bah, Katherine G. Holste, Guohua Xi, Richard F. Keep
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Neurosciences
Sara Diana Lolansen, Dagne Barbuskaite, Fenghui Ye, Jianming Xiang, Richard F. Keep, Nanna MacAulay
Summary: This study elucidated the molecular mechanisms underlying the development of hydrocephalus in spontaneously hypertensive rats (SHRs), and found that it is not associated with elevated intracranial pressure (ICP) and does not require increased cerebrospinal fluid (CSF) secretion or inefficient CSF drainage. This type of hydrocephalus is not life-threatening and occurs due to unknown disturbances in CSF dynamics.
FLUIDS AND BARRIERS OF THE CNS
(2023)
