ArticleActa neuropathologica communications2024
MANF protein expression is upregulated in immune cells in the ischemic human brain and systemic recombinant MANF delivery in rat ischemic stroke model demonstrates anti-inflammatory effects.
Article in Acta neuropathologica communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- The role of mesencephalic astrocyte-derived neurotrophic factor in digestive diseases.Annals of medicine · 2026Review
- MANF in the lateral septum dynamically regulates endoplasmic reticulum function in chronic stress response.Translational psychiatry · 2026Article
- Research on stem cell therapy for brain injury: A bibliometric and visual analysis (2009-2025).IBRO neuroscience reports · 2026Review
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Spatiotemporal Double-Edged Sword of Macrophages: Temporal Regulation of Neuroinflammation and Neurorepair in Ischemic Stroke.Journal of immunology research · 2026Review
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
- Upregulation of lncRNA CASC2 alleviates neuroinflammation in acute ischemic stroke and exhibits protective effects by targeting miR-155 (CASC2 role in AIS).European journal of medical research · 2025Article
- Cellular Communication Networks Mediated by Microglia in Ischemic Stroke.CNS neuroscience & therapeutics · 2025Review
- MANF improves cognitive function and attenuates neuroinflammation in APP/PS1 transgenic mice through the TLR4/MYD88/NF-κB signaling pathway.Journal of anesthesia and translational medicine · 2025Article
- Nanoparticle-Mediated Nose-to-Brain Delivery for Ischemic Stroke Therapy: Preclinical Insights.Pharmaceutics · 2025Review
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- Activation of the PERK/MANF/STAT3 Pathway in Astrocytes Promotes Synaptic Remodeling and Neurological Recovery in the Acute Phase After Stroke in Mice.Neural plasticity · 2025Article
- Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Mitigates Neuroinflammation and Cognitive Impairment by Modulating Glial Activation in Sepsis-Associated Encephalopathy.Neurochemical research · 2024Article
- Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesencephalic astrocyte-derived neurotrophic factor (MANF) has cytoprotective effects on various injuries, including cerebral ischemia, and it can promote recovery even when delivered intracranially several days after ischemic stroke. In the uninjured rodent brain, MANF protein is expressed almost exclusively in neurons, but post-ischemic MANF expression has not been characterized. We aimed to investigate how endogenous cerebral MANF protein expression evolves in infarcted human brains and rodent ischemic stroke models. During infarct progression, the cerebral MANF expression pattern both in human and rat brains shifted drastically from neurons to expression in inflammatory cells. Intense MANF immunoreactivity took place in phagocytic microglia/macrophages in the ischemic territory, peaking at two weeks post-stroke in human and one-week post-stroke in rat ischemic cortex. Using double immunofluorescence and mice lacking MANF gene and protein from neuronal stem cells, neurons, astrocytes, and oligodendrocytes, we verified that MANF expression was induced in microglia/macrophage cells in the ischemic hemisphere. Embarking on the drastic expression transition towards inflammatory cells and the impact of blood-borne inflammation in stroke, we hypothesized that exogenously delivered MANF protein can modulate tissue recovery processes. In an attempt to enhance recovery, we designed a set of proof-of-concept studies using systemic delivery of recombinant MANF in a rat model of cortical ischemic stroke. Intranasal recombinant MANF treatment decreased infarct volume and reduced the severity of neurological deficits. Intravenous recombinant MANF treatment decreased the levels of pro-inflammatory cytokines and increased the levels of anti-inflammatory cytokine IL-10 in the infarcted cortex one-day post-stroke. In conclusion, MANF protein expression is induced in activated microglia/macrophage cells in infarcted human and rodent brains, and this could implicate MANF's involvement in the regulation of post-stroke inflammation in patients and experimental animals. Moreover, systemic delivery of recombinant MANF shows promising immunomodulatory effects and therapeutic potential in experimental ischemic stroke.
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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 Socratic graph.