PMID- 30639504
OWN - NLM
STAT- MEDLINE
DCOM- 20200402
LR  - 20200617
IS  - 1878-1519 (Electronic)
IS  - 1569-9048 (Print)
IS  - 1569-9048 (Linking)
VI  - 265
DP  - 2019 Jul
TI  - Circulatory control of phrenic motor plasticity.
PG  - 19-23
LID - S1569-9048(18)30299-4 [pii]
LID - 10.1016/j.resp.2019.01.004 [doi]
AB  - Acute intermittent hypoxia (AIH) elicits distinct mechanisms of phrenic motor 
      plasticity initiated by brainstem neural network activation versus local (spinal) 
      tissue hypoxia. With moderate AIH (mAIH), hypoxemia activates the carotid body 
      chemoreceptors and (subsequently) brainstem neural networks associated with the 
      peripheral chemoreflex, including medullary raphe serotonergic neurons. Serotonin 
      release and receptor activation in the phrenic motor nucleus then elicits phrenic 
      long-term facilitation (pLTF). This mechanism is independent of tissue hypoxia, 
      since electrical carotid sinus nerve stimulation elicits similar 
      serotonin-dependent pLTF. In striking contrast, severe AIH (sAIH) evokes a spinal 
      adenosine-dependent, serotonin-independent mechanism of pLTF. Spinal tissue 
      hypoxia per se is the likely cause of sAIH-induced pLTF, since local tissue 
      hypoxia elicits extracellular adenosine accumulation. Thus, any physiological 
      condition exacerbating spinal tissue hypoxia is expected to shift the balance 
      towards adenosinergic pLTF. However, since these mechanisms compete for dominance 
      due to mutual cross-talk inhibition, the transition from serotonin to adenosine 
      dominant pLTF is rather abrupt. Any factor that compromises spinal cord 
      circulation will limit oxygen availability in spinal cord tissue, favoring a 
      shift in the balance towards adenosinergic mechanisms. Such shifts may arise 
      experimentally from treatments such as carotid denervation, or spontaneous 
      hypotension or anemia. Many neurological disorders, such as spinal cord injury or 
      stroke compromise local circulatory control, potentially modulating tissue 
      oxygen, adenosine levels and, thus, phrenic motor plasticity. In this brief 
      review, we discuss the concept that local (spinal) circulatory control and/or 
      oxygen delivery regulates the relative contributions of distinct pathways to 
      phrenic motor plasticity.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Perim, Raphael R
AU  - Perim RR
AD  - Center for Respiratory Research and Rehabilitation, Department of Physical 
      Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL, 
      32610, USA.
FAU - Mitchell, Gordon S
AU  - Mitchell GS
AD  - Center for Respiratory Research and Rehabilitation, Department of Physical 
      Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL, 
      32610, USA. Electronic address: gsmitche@phhp.ufl.edu.
LA  - eng
GR  - R01 HL069064/HL/NHLBI NIH HHS/United States
GR  - R37 HL069064/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190111
PL  - Netherlands
TA  - Respir Physiol Neurobiol
JT  - Respiratory physiology & neurobiology
JID - 101140022
RN  - 333DO1RDJY (Serotonin)
RN  - K72T3FS567 (Adenosine)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenosine/*metabolism
MH  - Animals
MH  - Cervical Cord/*physiology
MH  - Humans
MH  - *Hypoxia/metabolism/physiopathology
MH  - Neuronal Plasticity/*physiology
MH  - Oxygen/*metabolism
MH  - Phrenic Nerve/*physiology
MH  - *Respiratory Physiological Phenomena
MH  - Serotonin/*metabolism
MH  - Synaptic Potentials/*physiology
PMC - PMC7296465
MID - NIHMS1599990
OTO - NOTNLM
OT  - Acute intermittent hypoxia
OT  - Adenosine
OT  - Circulatory control
OT  - Respiratory motor plasticity
OT  - Serotonin
COIS- Conflicts of interest The authors declare no competing financial interests.
EDAT- 2019/01/15 06:00
MHDA- 2020/04/03 06:00
PMCR- 2020/06/16
CRDT- 2019/01/15 06:00
PHST- 2018/09/20 00:00 [received]
PHST- 2018/12/21 00:00 [revised]
PHST- 2019/01/10 00:00 [accepted]
PHST- 2019/01/15 06:00 [pubmed]
PHST- 2020/04/03 06:00 [medline]
PHST- 2019/01/15 06:00 [entrez]
PHST- 2020/06/16 00:00 [pmc-release]
AID - S1569-9048(18)30299-4 [pii]
AID - 10.1016/j.resp.2019.01.004 [doi]
PST - ppublish
SO  - Respir Physiol Neurobiol. 2019 Jul;265:19-23. doi: 10.1016/j.resp.2019.01.004. 
      Epub 2019 Jan 11.