ArticleNeuropharmacology2016
Tozasertib attenuates neuronal apoptosis via DLK/JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer's mice model.Scientific reports · 2025Article
- Computational Insights into the Polypharmacological Landscape of BCR-ABL Inhibitors: Emphasis on Imatinib and Nilotinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Moderate-intensity training can ameliorate the process of cardiac apoptosis induced by lithium drug consumption in male Wistar rats.Toxicology reports · 2024Article
- DLK signaling in axotomized neurons triggers complement activation and loss of upstream synapses.Cell reports · 2024Article
- Review
- iTRAQ-derived quantitative proteomics uncovers the neuroprotective property of bexarotene in a mice model of cerebral ischemia-reperfusion injury.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Advances in Recapitulating Alzheimer's Disease Phenotypes Using Human Induced Pluripotent Stem Cell-Based In Vitro Models.Brain sciences · 2022Review
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- c-Abl Tyrosine Kinase-Mediated Neuronal Apoptosis in Subarachnoid Hemorrhage by Modulating the LRP-1-Dependent Akt/GSK3β Survival Pathway.Journal of molecular neuroscience : MN · 2021Article
- Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival.Cells · 2021Article
- The ameliorative role of Physalis pubescens L. against neurological impairment associated with streptozotocin induced diabetes in rats.Metabolic brain disease · 2021Article
- Identifying drug candidates for hepatocellular carcinoma based on differentially expressed genes.American journal of translational research · 2020Article
- Inhibition of HDAC4 Attenuated JNK/c-Jun-Dependent Neuronal Apoptosis and Early Brain Injury Following Subarachnoid Hemorrhage by Transcriptionally Suppressing MKK7.Frontiers in cellular neuroscience · 2019Article
- Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage.Experimental and therapeutic medicine · 2018Article
- Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Review
- Critical role of EphA4 in early brain injury after subarachnoid hemorrhage in rat.Experimental neurology · 2017Article
- DLK silencing attenuated neuron apoptosis through JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.Neurobiology of disease · 2017Article
- Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats.Neuropharmacology · 2017Article
- X-linked inhibitor of apoptosis inhibits apoptosis and preserves the blood-brain barrier after experimental subarachnoid hemorrhage.Scientific reports · 2017Article
- Loss of GCN5 leads to increased neuronal apoptosis by upregulating E2F1- and Egr-1-dependent BH3-only protein Bim.Cell death & disease · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeSince tozasertib is neuroprotective for injured optic nerve, this study is intended to test whether tozasertib reduces early brain injury after subarachnoid hemorrhage (SAH) in a rat model.
methodsTwo hundred sixteen (216) male Sprague-Dawley rats were randomly subjected to endovascular perforation model of SAH and sham group. SAH grade, neurological score, and brain water content were measured at 24 and 72 h after SAH. Dual leucine zipper kinase (DLK) and its downstream factors, JNK-interacting protein 3 (JIP3), MA2K7, p-JNK/JNK (c-Jun N-terminal kinase), and apoptosis related proteins cleaved caspase-3 (CC-3), Bim, Bcl-2, and cleaved caspase-9 (CC-9) were analyzed by western blot at 24 h after SAH. Apoptotic cells were detected by terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). DLK small interfering RNA (siRNA), JIP3 siRNA and MA2K7 siRNA, the JNK, p38MAPK, and MEK inhibitors SP600125, SB203580, and PD98059 were used for intervention.
resultsTozasertib reduced neuronal apoptosis, attenuated brain edema and improved neurobehavioral deficits 24 and 72 h after SAH. At 24 h After SAH, DLK/JIP3/MA2K7/p-JNK/CC-3 expressions were elevated markedly and tozasertib reduced DLK, MA2K7/p-JNK/CC-3 expressions but enhanced JIP3 expression. In the presence of tozasertib, DLK/JIP3/MA2K7 siRNA and SP600125, SB203580 and PD98059 deteriorated the neurobehavioral deficits, brain edema and increased the expression of CC-3. SAH potentiated the expression of Bim, CC-9, and CC-3 but reduced Bcl-2, while tozasertib reduced expression of Bim, CC-9, and CC-3 but enhanced Bcl-2.
conclusionsTozasertib reduced neuronal apoptosis and improved outcome possibly via DLK/JIP3/MA2K7/JNK pathways after SAH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.