Innate Sleep Apnea in Spontaneously Hypertensive Rats Is Associated With Microvascular Rarefaction and Neuronal Loss in the preBötzinger Complex

Stroke. 2023 Dec;54(12):3141-3152. doi: 10.1161/STROKEAHA.123.044732. Epub 2023 Nov 27.


Background: Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia.

Methods: To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders: plethysmography and electroencephalographic/electromyographic recordings were used to assess sleep-wake state, breathing parameters, and sleep-disordered breathing; immunocytochemistry was used to assess vascular and neural health; the forced alteration Y maze and Barnes maze were used to assess short- and long-term memories, respectively; and an anesthetized preparation was used to assess baroreflex sensitivity.

Results: Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories.

Conclusions: Therefore, we postulate that hypertension induces SA through vascular damage in the respiratory column, culminating in neuronal loss in the inspiratory oscillator. This induction of SA, which, in turn, will independently exacerbate hypertension and neural inflammation, increases the rate of vascular dementia.

Keywords: cognition; hypertension; sleep apnea syndromes.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Dementia, Vascular* / complications
  • Humans
  • Hypertension* / complications
  • Microvascular Rarefaction* / complications
  • Rats
  • Rats, Inbred SHR
  • Sleep Apnea Syndromes* / complications