Abstract
We have examined the anti-angiogenic compound, angiostatin as a modulator of inflammatory reactivity and vascular responses and for neuroprotection in an animal model of Alzheimer’s disease (AD). Intra-hippocampal amyloidbeta (Aβ1-42) injection, relative to controls phosphate buffer saline (PBS) or reverse peptide Aβ42-1, increased gliosis in the molecular layer (ML) of rat hippocampus. Vascular remodeling was indicated from increased microvessel immunoreactivity (ir) in ML suggesting the possibility of an angiogenic response to peptide injection. Administration of Aβ1-42 also induced a loss of neurons in the granule cell region of hippocampus relative to controls. Treatment of peptide-injected rats with angiostatin was associated with a spectrum of modulatory effects including reduced microgliosis (by 34%), diminished microvessel ir (by 36%) and increased neuronal viability (by 31%) compared with peptide injection alone. Angiostatin treatment was ineffective in reducing astrogliosis induced by Aβ1-42 and applied alone the compound had no significant effect to alter gliosis, microvessel ir or neuronal viability compared with PBS control. In vitro, angiostatin significantly attenuated secretion of the pro-angiogenic agent, vascular endothelial growth factor (VEGF) in lipopolysaccharide (LPS)-stimulated THP-1 cells. Our findings provide novel evidence for a broad spectrum of angiostatin effects in an animal model of AD including actions to reduce inflammatory reactivity, stabilize vascular remodeling and confer neuroprotection. The overall effects of angiostatin are consistent with actions of the compound to inhibit microglial secretion of VEGF.
Keywords: AD animal model, intrahippocampal injection of Aβ1-42, microgliosis, vascular perturbations, angiostatin, antiangiogenic, vascular endothelial growth factor, immunohistochemistry
Current Alzheimer Research
Title:Actions of the Anti-Angiogenic Compound Angiostatin in an Animal Model of Alzheimer’s Disease
Volume: 10 Issue: 3
Author(s): Jae K Ryu, Jonathan P Little, Andis Klegeris, Nattinee Jantaratnotai and James G McLarnon
Affiliation:
Keywords: AD animal model, intrahippocampal injection of Aβ1-42, microgliosis, vascular perturbations, angiostatin, antiangiogenic, vascular endothelial growth factor, immunohistochemistry
Abstract: We have examined the anti-angiogenic compound, angiostatin as a modulator of inflammatory reactivity and vascular responses and for neuroprotection in an animal model of Alzheimer’s disease (AD). Intra-hippocampal amyloidbeta (Aβ1-42) injection, relative to controls phosphate buffer saline (PBS) or reverse peptide Aβ42-1, increased gliosis in the molecular layer (ML) of rat hippocampus. Vascular remodeling was indicated from increased microvessel immunoreactivity (ir) in ML suggesting the possibility of an angiogenic response to peptide injection. Administration of Aβ1-42 also induced a loss of neurons in the granule cell region of hippocampus relative to controls. Treatment of peptide-injected rats with angiostatin was associated with a spectrum of modulatory effects including reduced microgliosis (by 34%), diminished microvessel ir (by 36%) and increased neuronal viability (by 31%) compared with peptide injection alone. Angiostatin treatment was ineffective in reducing astrogliosis induced by Aβ1-42 and applied alone the compound had no significant effect to alter gliosis, microvessel ir or neuronal viability compared with PBS control. In vitro, angiostatin significantly attenuated secretion of the pro-angiogenic agent, vascular endothelial growth factor (VEGF) in lipopolysaccharide (LPS)-stimulated THP-1 cells. Our findings provide novel evidence for a broad spectrum of angiostatin effects in an animal model of AD including actions to reduce inflammatory reactivity, stabilize vascular remodeling and confer neuroprotection. The overall effects of angiostatin are consistent with actions of the compound to inhibit microglial secretion of VEGF.
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Cite this article as:
K Ryu Jae, P Little Jonathan, Klegeris Andis, Jantaratnotai Nattinee and G McLarnon James, Actions of the Anti-Angiogenic Compound Angiostatin in an Animal Model of Alzheimer’s Disease, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030004
DOI https://dx.doi.org/10.2174/1567205011310030004 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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