Review
Pharmacology & Pharmacy
Jose Martinez-Orgado, Maria Villa, Aaron del Pozo
Summary: CBD shows neuroprotective effects in newborn pigs and rodents with HIBI, modulating the major components of HIBI pathophysiology. It has the potential to be an effective treatment for neonatal HIBI.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hannah Mason, Ganesha Rai, Arina Kozyr, Nathaniel De Jonge, Emily Gliniewicz, Lars J. Berg, Gal Wald, Cayce Dorrier, Mark J. Henderson, Alexey Zakharov, Tristan Dyson, John Audley, Anthony M. Pettinato, Elias Carvalho Padilha, Pranav Shah, Xin Xu, Thomas L. Leto, Anton Simeonov, Kol A. Zarember, Dorian B. McGavern, John I. Gallin
Summary: NADPH oxidases (NOX's) and the reactive oxygen species (ROS) they produce are involved in various physiological processes, but excessive ROS production is associated with several diseases. In this study, a small molecule inhibitor, NCATS-SM7270, was developed and shown to specifically inhibit NOX2 activity in human and mouse granulocytes. The role of different NOX isoforms in mild traumatic brain injury (mTBI) was investigated, and it was found that NOX2 deficiency provided protection against mTBI pathology, while NOX4 deficiency exacerbated the injury. Treatment of mice with NCATS-SM7270 after mTBI reduced cortical cell death in a dose-dependent manner, and also partially reversed cortical damage in NOX4-deficient mice. These findings highlight the potential of NCATS-SM7270 as a specific inhibitor of NOX2 in protecting against NOX2-dependent cell death in mTBI.
Article
Neurosciences
Xin Sui, Hideyuki Yoshioka, Yuichiro Fukumoto, Kazuya Kanemaru, Hiroyuki Kinouchi
Summary: HAX-1 is a mitochondrial protein that plays a neuroprotective role against ischemic neuronal injury, and the downregulation of HAX-1 by NOX2-produced ROS can induce apoptosis after cerebral ischemia.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Duaah Almarzouq, May Al-Maghrebi
Summary: Oxidative stress, inflammation, and germ cell death are characteristic features of testicular ischemia reperfusion injury (tIRI), which can lead to testicular torsion and detorsion. This study investigated the impact of tIRI-activated NADPH oxidase (NOX) on the expression of the NLRP3 inflammasome pathway components. Results showed that tIRI caused spermatogenic damage, oxidative stress, and inflammation, as evidenced by altered antioxidant capacity, enzyme activity, and increased concentrations of inflammatory markers. Additionally, the components of the NLRP3 inflammasome pathway were upregulated during tIRI. Treatment with the NOX-specific inhibitor, apocynin, prevented oxidative stress, inflammation, and NLRP3 inflammasome activation during tIRI.
Article
Pediatrics
Kasper Jacobsen Kyng, Sven Wellmann, Verena Lehnerer, Laerke Hjollund Hansen, Jens Kuhle, Tine Brink Henriksen
Summary: This study investigated the changes of neurofilament light chain (NfL), a potential biomarker for brain injury, in a newborn piglet model of hypoxic-ischemic encephalopathy (HIE). The results showed an increase in NfL levels after hypoxia-ischemia (HI), with the highest values observed at 72 hours post-HI. NfL at 72 hours had high sensitivity and specificity for predicting moderate-severe brain injury.
FRONTIERS IN PEDIATRICS
(2023)
Article
Pediatrics
Daniel Alonso-Alconada, Pierre Gressens, Xavier Golay, Nicola J. Robertson
Summary: Hypoxia-ischemia can lead to a decrease in cell proliferation and neurogenesis in the neurogenic niche of the neonatal piglet, which may hinder the replacement of lost neurons and overall repair.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Kazuki Hatayama, Sydney Riddick, Fares Awa, Xiaodi Chen, Daniela Virgintino, Barbara S. Stonestreet
Summary: Exposure to hypoxic-ischemic insults in newborns can lead to severe neurological sequelae. This study investigated the changes in the neurovascular unit (NVU) after hypoxic-ischemic injury in neonatal rats. The findings showed increased vascular density, neurovascular remodeling, and changes in pericyte coverage and claudin-5 expression in different brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Qi-Qi Li, Jia-Ying Li, Ming Zhou, Zheng-Hong Qin, Rui Sheng
Summary: Cerebral ischemia is a disease caused by intracranial artery stenosis or occlusion, leading to ischemic necrosis of brain tissue, where neuroinflammation plays a key role.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Medicine, Research & Experimental
Natalia K. S. Lima, Wilka R. A. Farias, Marry A. S. Cirilo, Angelica G. Oliveira, Juliane S. Farias, Regina S. Aires, Humberto Muzi-Filho, Ana D. O. Paixao, Leucio D. Vieira
Summary: Acute renal injury induced by ischemia-reperfusion may lead to changes in proximal tubule ATPases and RAAS components, which are associated with renal Na+ retention and hypertension. NADPH oxidase plays a key role in these alterations.
Review
Biochemistry & Molecular Biology
Song Hee Lee, Minwoo Lee, Dong Gyun Ko, Bo Young Choi, Sang Won Suh
Summary: Oxidative stress plays a crucial role in acute neurological disorders, and NADPH oxidase is identified as a major source of cellular reactive oxygen species. Inhibiting NADPH oxidase can reduce neuronal injury in neurological diseases, while maintaining appropriate levels of NADPH oxidase is associated with proper neurogenesis after neuronal injury.
Article
Endocrinology & Metabolism
Fuxin Lu, Shujuan Fan, Andrea R. Romo, Duan Xu, Donna M. Ferriero, Xiangning Jiang
Summary: The study demonstrates that serum 24S-HC concentrations predict long-term brain structural and functional outcomes, suggesting it could be a novel and early blood biomarker for severity of neonatal HI brain damage and associated functional impairments.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Critical Care Medicine
Raymond C. Stetson, Jane E. Brumbaugh, Amy L. Weaver, Kristin C. Mara, Reese H. Clark, William A. Carey, Jennifer L. Fang
Summary: The study compared the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. The results showed that outborn status was not significantly associated with increased in-hospital mortality, but outborn neonates were more likely to experience seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement during their hospitalization. Further research is needed to understand the reasons behind these disparities and their potential impact on long-term neurodevelopmental outcomes.
Article
Critical Care Medicine
Daniel Agustin Godoy, Francisco Murillo-Cabezas, Jose Ignacio Suarez, Rafael Badenes, Paolo Pelosi, Chiara Robba
Summary: To ensure neuronal survival after severe traumatic brain injury, sufficient oxygen supply is crucial. Cerebral tissue oxygenation, which is determined by multiple physiological parameters, reflects the adequacy of cerebral perfusion. Brain tissue hypoxia occurs when oxygen supply is inadequate or cannot be utilized at the cellular level. Precision medicine and multimodal monitoring are important in individualized therapeutic interventions for specific brain damage.
Review
Biochemistry & Molecular Biology
Marina S. Hernandes, Qian Xu, Kathy K. Griendling
Summary: In this review, recent findings on the role of NADPH oxidases in BBB disruption induced by ischemic stroke were highlighted, emphasizing the impact of ROS on the function of the blood-brain barrier in neurological disorders.
Review
Medicine, General & Internal
Austin N. Smith, Michael Shaughness, Sean Collier, Deanna Hopkins, Kimberly R. Byrnes
Summary: Inflammation is a key component of the response to central nervous system injury, involving microglial activation and oxidative stress. While acute microglial activity may be beneficial, chronic inflammation and oxidative stress can harm other cells. This review evaluates current therapeutic approaches targeting microglia-mediated oxidative stress and suggests future research directions.
FRONTIERS IN MEDICINE
(2022)
Article
Neurosciences
Quentin Leyrolle, Fanny Decoeur, Cyril Dejean, Galadriel Briere, Stephane Leon, Ioannis Bakoyiannis, Emilie Baroux, Tony-Lee Sterley, Clementine Bosch-Bouju, Lydie Morel, Camille Amadieu, Cynthia Lecours, Marie-Kim St-Pierre, Maude Bordeleau, Veronique De Smedt-Peyrusse, Alexandran Sere, Leslie Schwendimann, Stephane Gregoire, Lionel Bretillon, Niyazi Acar, Corinne Joffre, Guillaume Ferreira, Raluca Uricaru, Patricia Thebault, Pierre Gressens, Marie-Eve Tremblay, Sophie Laye, Agnes Nadjar
Summary: Westernized dietary habits leading to reduced intake of n-3 PUFAs may be associated with neurodevelopmental disorders and disruptions in brain functional connectivity. Lifelong n-3 PUFA deficiency can interfere with oligodendrocyte maturation and myelination processes, resulting in long-term detrimental effects on white matter organization and hippocampus-prefrontal functional connectivity. Promoting developmental myelination through clemastine could rescue memory deficits in n-3 PUFA deficient animals.
Article
Pediatrics
Kathryn A. Martinello, Christopher Meehan, Adnan Avdic-Belltheus, Ingran Lingam, Tatenda Mutshiya, Qin Yang, Mustafa Ali Akin, David Price, Magdalena Sokolska, Alan Bainbridge, Mariya Hristova, Ilias Tachtsidis, Cally J. Tann, Donald Peebles, Henrik Hagberg, Tim G. A. M. Wolfs, Nigel Klein, Boris W. Kramer, Bobbi Fleiss, Pierre Gressens, Xavier Golay, Nicola J. Robertson
Summary: Therapeutic hypothermia did not show protection in a piglet model of inflammation-sensitized hypoxia-ischemia, as evidenced by aEEG, MRS, and immunohistochemistry. The immunosuppressive effects of hypothermia and the counteracting neuroinflammation by LPS may have led to the lack of efficacy of hypothermia in this context. Other immunomodulatory strategies may be more effective in treating inflammation-sensitized hypoxia-ischemia injuries.
PEDIATRIC RESEARCH
(2022)
Article
Clinical Neurology
Cindy Bokobza, Pooja Joshi, Anne-Laure Schang, Zsolt Csaba, Valerie Faivre, Amelie Montane, Anne Galland, Anouk Benmamar-Badel, Emmanuelle Bosher, Sophie Lebon, Leslie Schwendimann, Shyamala Mani, Pascal Dournaud, Valerie Besson, Bobbi Fleiss, Pierre Gressens, Juliette Van Steenwinckel
Summary: The study highlights the importance of miRNA-146b-5p in regulating microglial activation and white matter injury, which could be targeted to prevent and treat perinatal brain injuries effectively.
ANNALS OF NEUROLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Rochellys Diaz Heijtz, Pierre Gressens, Jonathan R. Swann
Summary: A novel therapeutic approach that targets neuroactive microbial metabolites in the gut shows promising results in improving behavior and safety in adolescents with autism spectrum disorder.
Review
Cell Biology
Barbara Hausott, Rudolf Glueckert, Anneliese Schrott-Fischer, Lars Klimaschewski
Summary: Intracellular signal transduction in response to growth factor receptor activation plays a key role in nervous system regeneration. The signal transduction regulators Sprouty (SPRY) and PTEN have been identified as important inhibitors of neuronal growth factor signaling. They interfere with major signaling pathways such as ERK or PI3K/Akt in neurons and glial cells. Understanding the effects of SPRY, PTEN, and their regulators in axonal regeneration can have significant implications for the treatment of neurological injuries.
Review
Biochemistry & Molecular Biology
Alice Jacquens, Edward J. Needham, Elisa R. Zanier, Vincent Degos, Pierre Gressens, David Menon
Summary: Head trauma is a common cause of disability in young adults, and cranial trauma in children has particularities in terms of epidemiology, mechanism, and physiopathology. The long-term repercussions of head trauma can be attributed to chronic neuroinflammation, a complex process involving various actors. Numerous studies have explored different anti-inflammatory therapies for traumatic brain injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Abi G. Yates, Elena Kislitsyna, Carla Alfonso Martin, Jiaying Zhang, Amy L. Sewell, Ane Goikolea-Vives, Valerie Cai, Lama F. Alkhader, Aleksander Skaland, Basil Hammond, Ralica Dimitrova, Dafnis Batalle, Cathy Fernandes, A. David Edwards, Pierre Gressens, Claire Thornton, Helen B. Stolp
Summary: In this study, the efficacy of montelukast in a mouse model of encephalopathy of prematurity (EoP) was evaluated. The results showed that montelukast can attenuate inflammation, improve grey matter neuropathology, and ameliorate behavior deficits, suggesting that early administration of repurposed montelukast may improve the development and outcome of EoP.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Neurosciences
Maria Sbeih, Benedicte Oules, Mansour Alkobtawi, Leslie Schwendimann, Qui Trung Ngo, Romain Fontaine, Natacha Teissier, Pierre Gressens, Selim Aractingi
Summary: Low doses of CCL2 can limit brain excitotoxic damage in post-partum mice by enhancing the recruitment of fetal microchimeric cells to the damaged hemisphere.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
Cindy Bokobza, Alice Jacquens, David Guenoun, Blandine Bianco, Anne Galland, Maxime Pispisa, Alexandra Cruz, Manuela Zinni, Valerie Faivre, Anne Roumier, Sophie Lebon, Tania Vitalis, Zsolt Csaba, Tifenn Le Charpentier, Leslie Schwendimann, Pierrette Young-Ten, Vincent Degos, Patricia Monteiro, Pascal Dournaud, Pierre Gressens, Juliette Van Steenwinckel
Summary: Approximately 15 million babies are born prematurely every year, and many of them will face motor and cognitive deficits in their lifetime. Systemic inflammation-induced neuroinflammation is a prominent process of perinatal brain injuries, especially white matter injuries (WMI). Serotonin and its receptors, particularly HTR7, play a significant role in inflammation regulation. The study suggests that targeting HTR7 may serve as an innovative therapeutic strategy to protect the developing brain from preterm brain injuries.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Cell Biology
Anne-Laure Schang, Juliette Van Steenwinckel, Zoi S. Ioannidou, Julia Lipecki, Charlotte Rich-Griffin, Kate Woolley-Allen, Nigel Dyer, Tifenn Le Charpentier, Patrick Schafer, Bobbi Fleiss, Sascha Ott, Delara Saberan-Djoneidi, Valerie Mezger, Pierre Gressens
Summary: This study provides a genome-wide understanding of the effects of neuroinflammation on oligodendrocyte precursor cells (OPCs). It reveals that neuroinflammation takes advantage of a primed epigenomic landscape in OPCs and induces abnormal expression of immune/inflammatory genes. Additionally, neuroinflammation counteracts the normal downregulation of the cell cycle pathway in maturing OPCs.
CELL DEATH & DISEASE
(2022)
Article
Immunology
Regis Dieckmann, Rille Pullerits, Johan Bylund, Anna Karlsson-Bengtsson, Hans Herlitz, Christine Wenneras, Pontus Thulin
Summary: Circulating antieosinophil antibodies (AEOSA) are associated with various autoimmune conditions and can be detected in patients' sera. Eosinophil peroxidase (EPX) is the main target recognized by AEOSA, indicating its high antigenic potential. The presence of concurrent AEOSA/ANCA positivity is observed in specific patient groups. Further research is needed to elucidate the association of AEOSA with autoimmunity.
JOURNAL OF IMMUNOLOGY RESEARCH
(2023)
Article
Critical Care Medicine
Helena Backman, Anders Blomberg, Anders Lundquist, Viktor Strandkvist, Sami Sawalha, Ulf Nilsson, Jonas Eriksson-Strom, Linnea Hedman, Caroline Stridsman, Eva Ronmark, Anne Lindberg
Summary: This study identified different FEV1 trajectories among individuals with and without airway obstruction, and found that the decline in FEV1 and mortality varied among these trajectories. The FEV1 trajectories and the relationship between low FVC and trajectory outcome in individuals with airway obstruction are of particular clinical interest.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Neurosciences
Juliette Van Steenwinckel, Cindy Bokobza, Mireille Laforge, Isabelle K. Shearer, Veronique E. Miron, Rejane Rua, Samantha M. Matta, Elisa L. Hill-Yardin, Bobbi Fleiss, Pierre Gressens
Summary: Approximately one in 10 babies are born preterm, and up to 50% of preterm infants develop encephalopathy of prematurity (EoP) that increases the risk of lifelong cognitive defects. Glial cells play a key role in the development of a healthy brain, but glial dysfunction is a hallmark of EoP. However, our understanding of glial biology is not sufficient for the development of effective neuroregenerative therapies.
Article
Cardiac & Cardiovascular Systems
Hina Taki, Jaakko Tuomilehto, Paul Zimmet, Abdonas Tamosiunas, Sudhir Kowlessur, Dianna J. Magliano, Jonathan E. Shaw, Stefan Soederberg, Ulf Nilsson
Summary: LVH is more common in individuals with hypertension, African ancestry, and/or low education level. These individuals are usually older, more likely to have hypertension, diabetes, known cardiovascular disease, and elevated levels of cholesterol and creatinine. Creole ethnicity, low education level, hypertension, known CVD, and elevated creatinine are associated with LVH. Individuals with untreated or uncontrolled hypertension are at a higher risk for LVH than those with well-controlled hypertension or normotension.
Review
Neurosciences
Rosa C. Paolicelli, Amanda Sierra, Beth Stevens, Marie-Eve Tremblay, Adriano Aguzzi, Bahareh Ajami, Ido Amit, Etienne Audinat, Ingo Bechmann, Mariko Bennett, Frederick Bennett, Alain Bessis, Knut Biber, Staci Bilbo, Mathew Blurton-Jones, Erik Boddeke, Dora Brites, Bert Brone, Guy C. Brown, Oleg Butovsky, Monica J. Carson, Bernardo Castellano, Marco Colonna, Sally A. Cowley, Colm Cunningham, Dimitrios Davalos, Philip L. De Jager, Bart de Strooper, Adam Denes, Bart J. L. Eggen, Ukpong Eyo, Elena Galea, Sonia Garel, Florent Ginhoux, Christopher K. Glass, Ozgun Gokce, Diego Gomez-Nicola, Berta Gonzalez, Siamon Gordon, Manuel B. Graeber, Andrew D. Greenhalgh, Pierre Gressens, Melanie Greter, David H. Gutmann, Christian Haass, Michael T. Heneka, Frank L. Heppner, Soyon Hong, David A. Hume, Steffen Jung, Helmut Kettenmann, Jonathan Kipnis, Ryuta Koyama, Greg Lemke, Marina Lynch, Ania Majewska, Marzia Malcangio, Tarja Malm, Renzo Mancuso, Takahiro Masuda, Michela Matteoli, Barry W. McColl, Veronique E. Miron, Anna Victoria Molofsky, Michelle Monje, Eva Mracsko, Agnes Nadjar, Jonas J. Neher, Urte Neniskyte, Harald Neumann, Mami Noda, Bo Peng, Francesca Peri, V. Hugh Perry, Phillip G. Popovich, Clare Pridans, Josef Priller, Marco Prinz, Davide Ragozzino, Richard M. Ransohoff, Michael W. Salter, Anne Schaefer, Dorothy P. Schafer, Michal Schwartz, Mikael Simons, Cody J. Smith, Wolfgang J. Streit, Tuan Leng Tay, Li-Huei Tsai, Alexei Verkhratsky, Rommy von Bernhardi, Hiroaki Wake, Valerie Wittamer, Susanne A. Wolf, Long-Jun Wu, Tony Wyss-Coray
Summary: Microglial research has made significant progress, but the current classification system fails to accurately describe their diversity, leading to misconceptions about their functions. To address this issue, a group of multidisciplinary experts has proposed a naming framework and recommendations to help researchers better understand and describe the different states and functions of microglia.
