ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2021
Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Angiotensin II exacerbates intracerebral hemorrhage in mice via heparin-like antithrombin activation and coagulation dysfunction.Nature communications · 2026Article
- TIGAR overexpression alleviates intracerebral hemorrhage injury in mice by suppressing ATF4/NOX4/p22phox-mediated oxidative stress and inflammation.Acta pharmacologica Sinica · 2026Article
- Tumor necrosis factor-α-stimulated gene 6 promotes hematoma clearance after intracerebral hemorrhage in a mouse model.Neural regeneration research · 2026Article
- M2 macrophage-derived exosomes delivering haptoglobin and interleukin-10 plasmids for synergistic therapy of intracerebral hemorrhage.Bioactive materials · 2026Article
- Inhibition of Microglial TRPV1 Ameliorates Brain Injury After Intracerebral Hemorrhage by Suppressing AMPK/PINK1-Mediated Mitophagy.CNS neuroscience & therapeutics · 2026Article
- Paricalcitol-mediated vitamin D receptor activation attenuates neuronal ferroptosis via cAMP-PKA-DRP1 signaling pathway after intracerebral hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Trigeminal nerve root compression induced neuroinflammatory response promotes mechanical allodynia through the CGRP/SP-Piezo2 axis via CaCellular & molecular biology letters · 2025Article
- Catalpalactone protects rats nerve function from hypoxic lesion by polarizing microglial cells toward M2 phenotype.European journal of medical research · 2025Article
- Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders.Molecules (Basel, Switzerland) · 2025Review
- Tachykinin Receptors and their Antagonists: Unraveling Their Role in Metabolic Disorders and Therapeutic Innovations.Current drug targets · 2025Review
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.Journal of neuroinflammation · 2024Article
- Fasting-mimicking diet alleviates inflammatory pain by inhibiting neutrophil extracellular traps formation and neuroinflammation in the spinal cord.Cell communication and signaling : CCS · 2023Article
- Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R/PKCδ pathway in a mouse model of intracerebral hemorrhage.Journal of neuroinflammation · 2022Article
- Application Effect of Whole-Process Seamless Nursing Model Based on Smart Healthcare Mode in Perioperative Period of Patients Undergoing Hematoma Removal.Journal of healthcare engineering · 2022Article
- Curcumin Restrains Oxidative Stress of After Intracerebral Hemorrhage in Rat by Activating the Nrf2/HO-1 Pathway.Frontiers in pharmacology · 2022Article
- Activation of LRP6 with HLY78 Attenuates Oxidative Stress and Neuronal Apoptosis via GSK3Oxidative medicine and cellular longevity · 2022Article
- Aprepitant Inhibits JNK and p38/MAPK to Attenuate Inflammation and Suppresses Inflammatory Pain.Frontiers in pharmacology · 2021Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Hematoma clearance is an important therapeutic target to improve outcome following intracerebral hemorrhage (ICH). Recent studies showed that Neurokinin receptor-1 (NK1R) inhibition exerts protective effects in various neurological disease models, but its role in ICH has not been explored. The objective of this study was to investigate the role of NK1R and its relation to hematoma clearance after ICH using an autologous blood injection mouse model. A total of 332 adult male CD1 mice were used. We found that the expression levels of NK1R and its endogenous ligand, substance P (SP), were significantly upregulated after ICH. Intraperitoneal administration of the NK1R selective antagonist, Aprepitant, significantly improved neurobehavior, reduced hematoma volume and hemoglobin levels after ICH, and promoted microglia polarization towards M2 phenotype. Aprepitant decreased phosphorylated PKC, p38MAPK, and NFκB p65, and downregulated M1 markers while upregulating M2 markers after ICH. Intracerebroventricular administration of the NK1R agonist, GR73632 or PKC agonist, phorbol 12-myristate 13-acetate (PMA) reversed the effects of Aprepitant. To demonstrate the upstream mediator of NK1R activation, we performed thrombin injection and found that it increased SP. Inhibiting thrombin suppressed SP and decreased M1 markers while increasing M2 microglia polarization. Thus, NK1R inhibition promoted hematoma clearance after ICH by increasing M2 microglial polarization via downregulating PKC/p38MAPK/NFκB signaling pathway, and thrombin may be a key upstream mediator of NK1R activation. Therapeutic interventions inhibiting NK1R signaling may be a new target for the treatment of ICH.
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