Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment

Ki Jung Kim, Juan Ramiro Diaz, Jessica L. Presa, P. Robinson Muller, Michael W. Brands, Mohammad B. Khan, David C. Hess, Ferdinand Althammer, Javier E. Stern, Jessica A. Filosa

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Chronic hypoperfusion is a key contributor to cognitive decline and neurodegenerative conditions, but the cellular mechanisms remain ill-defined. Using a multidisciplinary approach, we sought to elucidate chronic hypoperfusion-evoked functional changes at the neurovascular unit. We used bilateral common carotid artery stenosis (BCAS), a well-established model of vascular cognitive impairment, combined with an ex vivo preparation that allows pressurization of parenchymal arterioles in a brain slice. Our results demonstrate that mild (~ 30%), chronic hypoperfusion significantly altered the functional integrity of the cortical neurovascular unit. Although pial cerebral perfusion recovered over time, parenchymal arterioles progressively lost tone, exhibiting significant reductions by day 28 post-surgery. We provide supportive evidence for reduced adenosine 1 receptor-mediated vasoconstriction as a potential mechanism in the adaptive response underlying the reduced baseline tone in parenchymal arterioles. In addition, we show that in response to the neuromodulator adenosine, the action potential frequency of cortical pyramidal neurons was significantly reduced in all groups. However, a significant decrease in adenosine-induced hyperpolarization was observed in BCAS 14 days. At the microvascular level, constriction-induced inhibition of pyramidal neurons was significantly compromised in BCAS mice. Collectively, these results suggest that BCAS uncouples vessel-to-neuron communication—vasculo-neuronal coupling—a potential early event in cognitive decline.

Original languageEnglish (US)
Pages (from-to)1405-1422
Number of pages18
JournalGeroScience
Volume43
Issue number3
DOIs
StatePublished - Jun 2021

Keywords

  • A1R
  • Adenosine
  • Hypoperfusion
  • Myogenic tone
  • Neurovascular unit

ASJC Scopus subject areas

  • Aging
  • veterinary (miscalleneous)
  • Complementary and alternative medicine
  • Geriatrics and Gerontology
  • Cardiology and Cardiovascular Medicine

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