Review
Biochemistry & Molecular Biology
Matteo Haupt, Stefan T. Gerner, Mathias Baehr, Thorsten R. Doeppner
Summary: Despite significant progress in stroke therapy, ischemic stroke still imposes a high socioeconomic burden on industrialized countries. Current treatment paradigms focus on thrombolysis or thrombectomy, which are only suitable for a fraction of patients. Therefore, there is an urgent need for adjuvant therapeutic approaches like neuroprotection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Kemeng Zhao, Pengwei Wang, Xiaoguang Tang, Na Chang, Haonan Shi, Longfei Guo, Bingyi Wang, Pengfei Yang, Tiantian Zhu, Xinghua Zhao
Summary: Stroke is caused by ruptured or blocked cerebral blood vessels and subsequent disruption of brain blood circulation, resulting in rapid neurological deficits. The majority of stroke cases are ischemic strokes. Current treatments for ischemic stroke, such as t-PA thrombolytic therapy and surgical thrombectomy, can paradoxically lead to ischemia-reperfusion injury, exacerbating brain damage. Minocycline, a semi-synthetic tetracycline antibiotic, has demonstrated a wide range of neuroprotective effects independent of its antibacterial activity. In this article, we summarize the mechanisms underlying the protective effects of minocycline against cerebral ischemia-reperfusion injury, including modulation of oxidative stress, inflammatory response, excitotoxicity, programmed cell death, and blood-brain barrier injury. We also discuss the role of minocycline in alleviating stroke-related complications, providing a theoretical basis for its clinical application in cerebral ischemia-reperfusion injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Abdelrahman Y. Fouda, Wael Eldahshan, Zhimin Xu, Tahira Lemtalsi, Esraa Shosha, Syed A. H. Zaidi, Ammar A. Abdelrahman, Paul Ning-Man Cheng, S. Priya Narayanan, R. William Caldwell, Ruth B. Caldwell
Summary: The study demonstrates that systemic administration of PEG-A1 provides neuroprotection and offers an excellent route to deliver the drug to the retina and brain after acute injury.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Chemistry, Multidisciplinary
Alexandra Chovsepian, Daniel Berchtold, Katarzyna Winek, Uta Mamrak, Ines Ramirez Alvarez, Yanina Dening, Dominika Golubczyk, Luis Weitbrecht, Claudia Dames, Marine Aillery, Celia Fernandez-Sanz, Zdzislaw Gajewski, Marianne Dieterich, Miroslaw Janowski, Peter Falkai, Piotr Walczak, Nikolaus Plesnila, Andreas Meisel, Francisco Pan-Montojo
Summary: The study demonstrates that glycolic acid has a significant protective effect during ischemic reperfusion, reducing ischemic damage and improving functional outcomes. This protective effect may be achieved by counteracting the glutamate-induced increase in intracellular calcium.
Article
Biochemistry & Molecular Biology
Felicia P. Lotze, Matthias L. Riess
Summary: The study found that P188 has a protective and reparative effect on Mouse Brain Microvascular Endothelial Cells (MBEC) after traumatic brain injury (TBI), particularly in cases of mild-to-moderate injury. Furthermore, the presence of P188 can directly impact the cells' metabolic activity and total nitric oxide production. Therefore, P188 may be a potential drug for TBI treatment.
Article
Medicine, Research & Experimental
Shanshan Qiao, Dexin Yang, Xiaofeng Li, Weiping Li, Yuan Zhang, Wenlan Liu
Summary: The study reveals the crucial role of PAQR3 in ischemia/reperfusion injury, showing that silencing PAQR3 protects neuronal cells and improves cell survival by inhibiting the apoptosis pathway. Knockdown of PAQR3 significantly attenuates apoptosis and increases cell viability, offering a novel therapeutic target for preventing cerebral ischemia/reperfusion injury.
Review
Neurosciences
Bin Jiang, Xiaojie Wang, Jianping Ma, Aminah Fayyaz, Li Wang, Pei Qin, Yuchuan Ding, Xunming Ji, Sijie Li
Summary: Stroke is a major global health concern, and remote ischemic conditioning (RIC) has emerged as a convenient, simple, non-intrusive, and effective method for treating stroke. RIC improves brain tolerance to ischemia, increases cerebral blood perfusion, and reduces the risk of brain tissue damage.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Neurosciences
Diego Pichardo-Rojas, Pavel Salvador Pichardo-Rojas, Jose Manuel Cornejo-Bravo, Aracely Serrano-Medina
Summary: The primary mechanism for neuron death after an ischemic stroke is excessive depolarization leading to NMDA-mediated calcium entry and subsequent cellular death. Memantine, a non-competitive NMDA receptor antagonist, has shown promising preclinical and clinical evidence as a neuroprotective drug for ischemic stroke. Clinical trials have found that high-dose memantine can improve neurological function and aphasia in poststroke patients, but limitations such as small sample sizes limit the impact of these findings. Further research is needed to conclusively determine if memantine improves outcomes in patients post-ischemic stroke.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Clinical Neurology
E. M. Vos, V. J. Geraedts, A. van der Lugt, D. W. J. Dippel, M. J. H. Wermer, J. Hofmeijer, A. C. G. M. van Es, Y. B. W. E. M. Roos, C. M. P. C. D. Peeters-Scholte, I. R. van den Wijngaard
Summary: Neuroprotective agents in combination with reperfusion therapy have shown some efficacy in acute ischemic stroke, but relevant studies are limited. Future research should use standardized outcome measures and combine neuroprotective agents with reperfusion therapy.
FRONTIERS IN NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Shen Li, Marc Fisher
Summary: Recanalization therapy with endovascular procedures has significantly improved the treatment of acute ischemic stroke. Large animal models are necessary to bridge the gap between rodent and human studies in order to optimize preclinical and translational stroke research. Recent progress in reproducing ischemic and reperfusion mechanisms in large animal stroke models through surgical and endovascular methods is highlighted. The importance of optimizing large animal stroke modeling is emphasized through the evaluation of new findings from clinical trials and preclinical experiments, as well as adhering to established recommendations and principles.
Review
Pharmacology & Pharmacy
Zhizhun Mo, Zhongyi Zeng, Yuxiang Liu, Linsheng Zeng, Jiansong Fang, Yinzhong Ma
Summary: Stroke is a leading cause of death and survivors often suffer from severe neurological and motor deficits. The Wnt signaling pathway has been found to play a key role in the pathogenesis of stroke and reactivating this pathway can have significant therapeutic effects. A comprehensive understanding of the role of Wnt signaling in different cell types can help evaluate its potential value for stroke treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Editorial Material
Endocrinology & Metabolism
Di Wu, Jian Chen, Xuxiang Zhang, Roxanne Ilagan, Yuchuan Ding, Xunming Ji
Summary: Selective therapeutic cooling is a promising technique for reducing final infarct volume and improving outcomes in ischemic stroke. However, more targeted induction of brain hypothermia and mitigating potential side effects related to inducing hypothermia may be necessary to enhance the benefits of this method.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Nutrition & Dietetics
Paula Garcia-Rodriguez, Feifei Ma, Carmen del Rio, Marina Romero-Bernal, Ana M. Najar, Maria de la Luz Cadiz-Gurrea, Francisco Javier Leyva-Jimenez, Laura Ramiro, Paloma Menendez-Valladares, Soledad Perez-Sanchez, Antonio Segura-Carretero, Joan Montaner
Summary: This study investigated the protective effect of Salicornia ramosissima, a plant rich in polyphenols, against hypoxia and brain ischemia. The results showed that the ethanolic extract of S. ramosissima could protect flies and mice from the harmful effects of hypoxia and reduce infarct volume. Phytochemical analysis revealed the presence of 50 compounds in the extract. These findings suggest that S. ramosissima could be developed as an effective food supplement for the prevention or treatment of neurovascular disorders.
Article
Biochemistry & Molecular Biology
Siqi Wang, Yuting Chen, Chen Xia, Chunyan Yang, Jian Chen, Li Hai, Yong Wu, Zhongzheng Yang
Summary: Glycosylated quercetin (2Glu-Que) significantly enhances the neuroprotective effects of quercetin by improving water solubility, stability, and cell viability, making it a promising candidate in neuroprotection.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Clinical Neurology
Johanna Ospel, Nathaniel Rex, Sandeep Kandregula, Mayank Goyal
Summary: In clinical practice, achieving recanalization of occluded blood vessels is an important goal for treating acute ischemic stroke patients. However, successful recanalization does not guarantee successful reperfusion of ischemic tissue, and various post-recanalization tissue damage mechanisms can impair patient outcomes. Understanding the prevalence and importance of these mechanisms is crucial for identifying promising cerebroprotectants and designing effective clinical trials. Serial human MRI studies combined with animal studies could provide valuable insights and help accelerate the translation of cerebroprotective agents from bench to bedside.
Article
Neurosciences
Yongfang Zhao, Cheng Ma, Caixia Chen, Sicheng Li, Yangfan Wang, Tuo Yang, R. Anne Steler, Michael V. L. Bennett, C. Edward Dixon, Jun Chen, Yejie Shi
Summary: Traumatic brain injury (TBI) induces inflammation in the brain, resulting in secondary injury and hindered tissue repair. This study investigates the role of transcription factor STAT1 in inflammatory responses after TBI and suggests it as a potential therapeutic target. The inhibition of STAT1 reduces inflammation and improves outcomes in TBI.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Kristin M. Miner, Anuj S. Jamenis, Tarun N. Bhatia, Rachel N. Clark, Dhivyaa Rajasundaram, Sylvie Sauvaigo, Daniel M. Mason, Jessica M. Posimo, Nevil Abraham, Brett A. DeMarco, Xiaoming Hu, R. Anne Stetler, Jun Chen, Laurie H. Sanders, Kelvin C. Luk, Rehana K. Leak
Summary: This study reveals a potential sex-biased link between alpha-synucleinopathy and APE1 in mice and humans, suggesting that APE1 may play a role in the formation of alpha-synuclein inclusions. Further studies are needed to understand how APE1 modifies alpha-synuclein inclusions and how alpha-synucleinopathy and biological sex interact to modify APE1.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kandarp M. Dave, Donna B. Stolz, Venugopal R. Venna, Victoria A. Quaicoe, Michael E. Maniskas, Michael John Reynolds, Riyan Babidhan, Duncan X. Dobbins, Maura N. Farinelli, Abigail Sullivan, Tarun N. Bhatia, Hannah Yankello, Rohan Reddy, Younsoo Bae, Rehana K. Leak, Sruti S. Shiva, Louise D. McCullough, Devika S. Manickam
Summary: Ischemic stroke causes brain endothelial cell death and damages blood-brain barrier integrity. Utilizing extracellular vesicles from brain endothelial cells and exogenous heat shock protein, this study aimed to increase cell survival and preserve tight junction integrity. The study demonstrated that medium-to-large-sized extracellular vesicles transferred their mitochondrial load to recipient cells, resulting in increased ATP levels and improved mitochondrial function. This approach showed promising results in reducing brain infarct size in a mouse model of ischemic stroke.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Neurosciences
Hongjian Pu, Yangfan Wang, Tuo Yang, Rehana K. Leak, R. Anne Stetler, Fang Yu, Wenting Zhang, Yejie Shi, Xiaoming Hu, Ke-jie Yin, T. Kevin Hitchens, C. Edward Dixon, Michael V. L. Bennett, Jun Chen
Summary: Traumatic brain injury (TBI) often leads to intractable psychiatric disorders and long-term changes in affect, such as anxiety. This study aimed to investigate the effect of repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles on affective symptoms after TBI in mice. The results showed that IL-4 delivery attenuated anxiety-like behaviors and protected against neuronal loss and fiber tract damage in key limbic structures. It also promoted a beneficial microglia/macrophage phenotype, which was correlated with long-term behavioral improvements. These findings suggest that IL-4 holds promise for managing mood disturbances following TBI.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Chenghao Jin, Yejie Shi, Ligen Shi, Rehana K. Leak, Wenting Zhang, Kong Chen, Qing Ye, Sulaiman Hassan, Junxuan Lyu, Xiaoming Hu, R. Anne Stetler, Michael V. L. Bennett, Jun Chen
Summary: We used single-cell transcriptomics to investigate the mechanisms underlying age-related decline in cerebral vasculature and white matter repair/regrowth after stroke in young versus aged mice. Our findings demonstrate that aging impairs the early prorepair transcriptional reprogramming of angiogenesis and oligodendrogenesis in the brain after stroke. Microglia and macrophages play a crucial role in promoting angiogenesis and oligodendrogenesis, but this reparative cell-cell cross talk is hindered in aged brains. Transplantation of microglia and macrophages from young brains into aged stroke brains partially restored angiogenesis and oligodendrogenesis and improved neurological functions. These findings provide insights into potential targets for improving stroke recovery in the aged.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Clinical Neurology
Wenting Zhang, Hongjian Pu, Xiaoming Hu, Yejie Shi, Rehana K. Leak, R. Anne Stetler, Qing Ye, Junxuan Lyu, Feng Zhang, Lawrence R. Wechsler, Jun Chen
Summary: Experimental evidence suggests that transplantation of bone marrow-derived human mesenchymal stem cells (hMSCs) improves stroke recovery in aged mice by promoting brain repair, mainly through enhanced microvascular regeneration and white matter restoration.
Article
Clinical Neurology
Kristin M. Miner, Anuj S. Jamenis, Tarun N. Bhatia, Rachel N. Clark, Muslim Abbas, Kelvin C. Luk, Rehana K. Leak
ACTA NEUROPATHOLOGICA
(2023)
Editorial Material
Neurosciences
Rehana K. Leak, Devika Soundara-Manickam, Xiaoming Hu, Jun Chen, Khalid M. Kamal, Wilson S. Meng
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Editorial Material
Neurosciences
Rehana K. Leak, Devika Soundara-Manickam, Xiaoming Hu, Jun Chen, Khalid M. Kamal, Wilson S. S. Meng
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Yashika S. Kamte, Manisha N. Chandwani, Natalie M. London, Chloe E. Potosnak, Rehana K. Leak, Lauren A. O'Donnell
Summary: Viral infections of the central nervous system (CNS) in children can lead to long-term neurological deficits. This study used a mouse model of measles virus infection and found that the virus caused a decrease in neural stem cell (NSC) numbers during childhood, but NSC numbers ultimately stabilized in adulthood. These findings provide insight into the potential cellular mechanisms underlying long-term neurological deficits in survivors of childhood CNS infections.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Anna J. Voss, Samantha N. Lanjewar, Maureen M. Sampson, Alexia King, Emily J. Hill, Anson Sing, Caitlin Sojka, Tarun N. Bhatia, Jennifer M. Spangle, Steven A. Sloan
Summary: The authors propose a data-driven framework to identify ligand-receptor pairs promoting astrogenesis and validate their effects in human cortical organoids and fetal progenitor cells. They used transcriptomic data to identify and functionally test five ligand-receptor pairs that synergistically drive human astrogenesis. Their study confirms that these ligands act cooperatively and converge on the mTORC1 signaling pathway, leading to transcriptomic and morphological changes in astrocyte development.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Tarun N. Bhatia, Anuj S. Jamenis, Muslim Abbas, Rachel N. Clark, Kristin M. Miner, Manisha N. Chandwani, Roxanne E. Kim, William Hilinski, Lauren A. O'Donnell, Kelvin C. Luk, Yejie Shi, Xiaoming Hu, Jun Chen, Jeffrey L. Brodsky, Rehana K. Leak
Summary: Reactive microglia are observed in aging and Lewy body disorders, and resetting these cells with the CSF1R inhibitor PLX5622 may have therapeutic potential. In the PFF model of alpha-synuclein fibrils, short-term dietary exposure to PLX5622 reduced inclusion numbers and insoluble alpha-synuclein in aged males, but raised inclusion sizes in both sexes. Transient delivery of PLX5622 also improved spatial reference memory in PFF-infused aged mice.
NEUROBIOLOGY OF DISEASE
(2023)