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Bergapten attenuates microglia-mediated neuroinflammation and ischemic brain injury by targeting Kv1.3 and Carbonyl reductase 1
Eur J Pharmacol. 2022 Sep 1:175242. doi: 10.1016/j.ejphar.2022.175242. Online ahead of print.ABSTRACTMicroglia-mediated neuroinflammation plays a vital role in the pathogenesis of ischemic stroke, which serves as a prime target for developing novel therapeutic agent. However, feasible and effective agents for controlling neuroinflammation are scarce. Bergapten were acknowledged to hold therapeutic potential in restricting inflammation in multiple diseases, including peripheral neuropathy, migraine headaches and osteoarthritis. Here, we aimed to investigate the impact of bergapten on microglia-mediated neuroinflammation and...
Source: European Journal of Pharmacology - September 4, 2022 Category: Drugs & Pharmacology Authors: Shenghan Gao Xinxin Zou Zibu Wang Xin Shu Xiang Cao Shengnan Xia Pengfei Shao Xinyu Bao Haiyan Yang Yun Xu Pinyi Liu Source Type: research

CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis
Cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most common monogenic form of small vessel disease characterized by migraine with aura, leukoaraiosis, strokes, and dementia. CADASIL mutations cause cerebrovascular dysfunction in both animal models and humans. Here, we showed that 2 different human CADASIL mutations (Notch3 R90C or R169C) worsen ischemic stroke outcomes in transgenic mice; this was explained by the higher blood flow threshold to maintain tissue viability compared with that in wild type (WT) mice. Both mutants developed larger infarcts and worse neurol...
Source: Journal of Clinical Investigation - April 15, 2022 Category: Biomedical Science Authors: Fumiaki Oka, Jeong Hyun Lee, Izumi Yuzawa, Mei Li, Daniel von Bornstaedt, Katharina Eikermann-Haerter, Tao Qin, David Y. Chung, Homa Sadeghian, Jessica L. Seidel, Takahiko Imai, Doga Vuralli, Rosangela M. Platt, Mark T. Nelson, Anne Joutel, Sava Sakadzic, Source Type: research

Janssen Demonstrates Commitment to Advancing Science and Innovation in the Treatment of Solid Tumors at ESMO Annual Congress
September 8, 2021 (RARITAN, N.J.) – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that more than ten data presentations from its lung cancer, bladder cancer and prostate cancer portfolio and pipeline will be featured during the European Society for Medical Oncology (ESMO) Annual Congress 2021 virtual meeting, September 16–21. Further details about these data and the science Janssen is advancing will be made available throughout ESMO via the Janssen Oncology Virtual Newsroom.“With a diverse oncology portfolio and pipeline spanning bladder cancer, lung cancer and prostate cancer, Janssen...
Source: Johnson and Johnson - September 8, 2021 Category: Pharmaceuticals Tags: Innovation Source Type: news

Janssen Announces U.S. FDA Approval of INVEGA HAFYERA ™(6-month paliperidone palmitate), First and Only Twice-Yearly Treatment for Adults with Schizophrenia
TITUSVILLE, N.J., Sept. 1, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) has approved long-acting atypical antipsychotic INVEGA HAFYERA™ (6-month paliperidone palmitate), the first-and-only twice-yearly injectable for the treatment of schizophrenia in adults. Before transitioning to INVEGA HAFYERA™, patients must be adequately treated with INVEGA SUSTENNA® (1-month paliperidone palmitate) for at least four months, or INVEGA TRINZA® (3-month paliperidone palmitate) for at least one 3-month injection cycle.1 The FDA approval of INVEGA ...
Source: Johnson and Johnson - September 1, 2021 Category: Pharmaceuticals Tags: Innovation Source Type: news

Neocortical in vivo focal and spreading potassium responses and the influence of astrocytic gap junctional coupling.
Abstract Raised extracellular potassium ion (K+) concentration is associated with several disorders including migraine, stroke, neurotrauma and epilepsy. K+ spatial buffering is a well-known mechanism for extracellular K+ regulation/distribution. Astrocytic gap junction-mediated buffering is a controversial candidate for K+ spatial buffering. To further investigate the existence of a K+ spatial buffering and to assess the involvement of astrocytic gap junctional coupling in K+ redistribution, we hypothesized that neocortical K+ and concomitant spreading depolarization (SD)-like responses are controlled by powerful...
Source: Neurobiology of Disease - November 2, 2020 Category: Neurology Authors: EbrahimAmini A, Bazzigaluppi P, Aquilino MS, Stefanovic B, Carlen PL Tags: Neurobiol Dis Source Type: research

Sodium Fluctuations in Astroglia and Their Potential Impact on Astrocyte Function
Astrocytes are the main cell type responsible for the regulation of brain homeostasis, including the maintenance of ion gradients and neurotransmitter clearance. These processes are tightly coupled to changes in the intracellular sodium (Na+) concentration. While activation of the sodium-potassium-ATPase (NKA) in response to an elevation of extracellular K+ may decrease intracellular Na+, the cotransport of transmitters, such as glutamate, together with Na+ results in an increase in astrocytic Na+. This increase in intracellular Na+ can modulate, for instance, metabolic downstream pathways. Thereby, astrocytes are capable ...
Source: Frontiers in Physiology - August 11, 2020 Category: Physiology Source Type: research

Role of TREK-1 in Health and Disease, Focus on the Central Nervous System
Conclusion and Perspectives Since their cloning 20 years ago, the physiological importance of TREK-1 channels has continued to grow (Figure 3). Today, TREK-1 channels have been shown to be important and their presence is essential in a number of physiopathological processes. Their involvement in these different processes demonstrate the necessity to design pharmacological modulators, activators or inhibitors, of these channels to correct any TREK-1-related dysfunctions. Despites a number of studies and many molecule screenings, only few putative new drugs were identified. The activators belonging to the ML and BL series ...
Source: Frontiers in Pharmacology - April 10, 2019 Category: Drugs & Pharmacology Source Type: research

The effects of cerebral curvature on cortical spreading depression
In this study a large scale numerical NVC model of multiple NVUs is coupled to a vascular tree simulating a two-dimensional cerebral tissue slice. This model is extended with a spatial Gaussian curvature mapping that can simulate the highly folded nature of the human cortex. For a flat surface comparable to a lissencephalic cortex the model can simulate propagating waves of high extracellular K+ travelling radially outwards from a stimulated area at approximately 6.7 mm/min, corresponding well with multiple experimental results. The high K+ concentration induces a corresponding wave of vasoconstriction (with decreased bloo...
Source: Journal of Theoretical Biology - April 9, 2019 Category: Biology Source Type: research

Control of spreading depression with electrical fields - Whalen AJ, Xiao Y, Kadji H, Dahlem MA, Gluckman BJ, Schiff SJ.
Spreading depression or depolarization is a large-scale pathological brain phenomenon related to migraine, stroke, hemorrhage and traumatic brain injury. Once initiated, spreading depression propagates across gray matter extruding potassium and other activ...
Source: SafetyLit - June 12, 2018 Category: International Medicine & Public Health Tags: Ergonomics, Human Factors, Anthropometrics, Physiology Source Type: news

Activity-dependent changes in transporter and potassium currents in hippocampal astrocytes.
Abstract Astrocytes are involved in maintenance of synaptic microenvironment by glutamate uptake and K(+) clearance. These processes are associated with net charge transfer across the membrane and therefore can be recorded as glutamate transporter (IGluT) and K(+) (IK) currents. It has been previously shown that the blockade of IK with BaCl2 enhances the IGluT. Here we show that activity-dependent facilitation (5 stimuli at 50Hz) of IGluT was not significantly different in BaCl2 compared to facilitation of IGluT isolated by post-hoc subtraction of IK. Nevertheless, BaCl2 abolished the activity-dependent prolongati...
Source: Brain Research Bulletin - September 7, 2017 Category: Neurology Authors: Lebedeva A, Plata A, Nosova O, Tyurikova O, Semyanov A Tags: Brain Res Bull Source Type: research