Intranasal Losartan Decreases Perivascular Beta Amyloid, Inflammation, and the Decline of Neurogenesis in Hypertensive Rats

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Henning J DrewsLusine Danielyan

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 find...Continue Reading

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Citations

May 17, 2019·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Duraisamy KempurajAsgar Zaheer
Nov 10, 2020·Journal of Alzheimer's Disease : JAD·Xinquan LiBiao Cai
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Mar 7, 2021·Pharmaceuticals·Henning Johannes DrewsLusine Danielyan
Jan 20, 2022·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Luling WangXunming Ji

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Methods Mentioned

BETA
transgenic
FACS
light scattering
PCR
PCRs
electrophoresis
fluorescence microscopy
Protein Assay
Assay
Flow cytometry

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