ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2019
Intranasal Losartan Decreases Perivascular Beta Amyloid, Inflammation, and the Decline of Neurogenesis in Hypertensive Rats.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Current updates on latest basic research of scientific relevance in hypertensive dementia.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease.Stem cell research & therapy · 2025Review
- The Use of Antihypertensive Medication and In Vivo Alzheimer's Disease Pathology.Annals of neurology · 2025Article
- Cardiac biomarkers are associated with increased risks of adverse clinical outcomes after ischemic stroke.Journal of neurology · 2024Article
- Influencing factors of glymphatic system during perioperative period.Frontiers in neuroscience · 2024Review
- Angiotensin Receptor Blockers and Cognition: a Scoping Review.Current hypertension reports · 2024Article
- Propionic and valproic acids have an impact on bacteria viability, proton flux and ATPase activity.Journal of bioenergetics and biomembranes · 2023Article
- Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia.Pharmaceutics · 2023Review
- Review
- Angiotensin receptor blocker use is associated with upregulation of the memory-protective angiotensin type 4 receptor (ATGeroScience · 2023Article
- Synthetic PPAR Agonist DTMB Alleviates Alzheimer's Disease Pathology by Inhibition of Chronic Microglial Inflammation in 5xFAD Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Intranasal neprilysin rapidly eliminates amyloid-beta plaques, but causes plaque compensations: the explanation why the amyloid-beta cascade may fail?Neural regeneration research · 2022Review
- Phenotype Shifting in Astrocytes Account for Benefits of Intra-Arterial Selective Cooling Infusion in Hypertensive Rats of Ischemic Stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Pharmaceutical Potential of Casein-Derived Tripeptide Met-Lys-Pro: Improvement in Cognitive Impairments and Suppression of Inflammation in APP/PS1 Mice.Journal of Alzheimer's disease : JAD · 2022Article
- Elevated Serum Lactate Dehydrogenase Predicts Unfavorable Outcomes After rt-PA Thrombolysis in Ischemic Stroke Patients.Frontiers in neurology · 2022Article
- Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer's Mice.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The use of angiotensin-converting enzyme inhibitors vs. angiotensin receptor blockers and cognitive decline in Alzheimer's disease: the importance of blood-brain barrier penetration and APOE ε4 carrier status.Alzheimer's research & therapy · 2021Article
- Intranasal Delivery of Collagen-Loaded Neprilysin Clears Beta-Amyloid Plaques in a Transgenic Alzheimer Mouse Model.Frontiers in aging neuroscience · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The contribution of the local angiotensin receptor system to neuroinflammation, impaired neurogenesis, and amyloid beta (Aβ) accumulation in Alzheimer's disease (AD) and in hypertension is consistent with the remarkable neuroprotection provided by angiotensin receptor blockers (ARBs) independent of their blood pressure-lowering effect. Considering the causal relationship between hypertension and AD and that targeting cerebrovascular pathology with ARBs does not necessarily require their systemic effects, we tested intranasal losartan in the rat model of chronic hypertension (spontaneously hypertensive stroke-prone rats, SHRSP). Intranasal losartan at a subdepressor dose decreased mortality, neuroinflammation, and perivascular content of Aβ by enhancing key players in its metabolism and clearance, including insulin-degrading enzyme, neprilysin, and transthyretin. Furthermore, this treatment improved neurologic deficits and increased brain IL-10 concentration, hippocampal cell survival, neurogenesis, and choroid plexus cell proliferation in SHRSP. Losartan (1 μM) also reduced LDH release from cultured astroglial cells in response to toxic glutamate concentrations. This effect was completely blunted by IL-10 antibodies. These findings suggest that intranasal ARB treatment is a neuroprotective, neurogenesis-inducing, and Aβ-decreasing strategy for the treatment of hypertensive stroke and cerebral amyloid angiopathy acting at least partly through the IL-10 pathway.
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