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The Role of Neuroinflammation in Post-Exertional Malaise Among Chronic Multisymptom Illness
The Role of Neuroinflammation in Post-Exertional Malaise Among Chronic Multisymptom Illnes...
The Role of Neuroinflammation in Post-Exertional Malaise Among Chronic Multisymptom Illness

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자료유형  
 학위논문 서양
최종처리일시  
20260202105126
ISBN  
9798291552421
DDC  
616
저자명  
Ninneman, Jacob V.
서명/저자  
The Role of Neuroinflammation in Post-Exertional Malaise Among Chronic Multisymptom Illness
발행사항  
[Sl] : The University of Wisconsin - Madison, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
210 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-02, Section: B.
주기사항  
Advisor: Cook, Dane B.
학위논문주기  
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
초록/해제  
요약Introduction: Chronic Multisymptom Illnesses (CMIs) (e.g., Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Gulf War Illness (GWI)) are characterized by chronic fatigue, pain, and neurocognitive complaints without a clear underlying pathology. Instead of experiencing the salubrious response typically associated with exercise, those with CMI experience a worsening of symptoms post-exercise, termed post-exertional malaise (PEM). Physiology at rest has not adequately explained CMI symptoms; therefore experimental models of PEM are used to better understand both disease pathophysiology and symptom worsening. The limited evidence available suggests that exercise can stimulate peripheral inflammation in CMI, although the data are mixed. It is unknown whether exercise induce central nervous system inflammation (i.e. neuroinflammation).Purpose: To investigate neuroinflammation at rest and in response to an acute exercise challenge in CMI.Methods: 14 CMI (6 Long COVID, 6 ME/CFS, and 2 GWI) and 14 age and sex matched controls (CON) were recruited. Inclusion criteria consisted of meeting the World Health Organization criteria for Long COVID, the Canadian Consensus Criteria for ME/CFS, and the Kansas Case definition for GWI. Positron emission tomography (PET) imaging and symptom measurement, took place one week prior to and 24 hours following a standardized exercise test. Additionally, symptoms measurement occurred for one week post exercise. PET imaging consisted of a 70 minute dynamic scan with a third generation translocator protein radiotracer - 11C-ER176. Exercise consisted of 30 minutes of moderate intensity cycling (70% Heart Rate Reserve) with continuous collection of the cardiometabolic response with a Parvo metabolic cart. All PET images were normalized to a standardized space and corrected for the injected dose and whole brain binding. Groups were compared at baseline and post-exercise with an analysis of covariance (ANCOVA) controlling for genotype or genotype and age and sex. A repeated measures ANCOVA controlling for either genotype or genotype, age, and sex was used to compare the response to exercise between CMI and CON. Relationships with symptoms were tested with multiple linear regressions.Results: As expected, CMI reported worse fatigue, pain, mental and physical functioning, sleep, mood, as well as lower levels of physical activity relative to CON. CMI and CON were able to maintain their prescribed intensity for a similar percentage of the test (CMI: 83.5%, CON: 90.1, p = 0.17). Cardiometabolic and perceptual responses were similar with only average fatigue being significantly different between groups. Significant group x time interactions were identified for fatigue (F(2,81) = 6.38, p = 0.003), pain (F(2,81) =6.06, p = 0.004), and neurocognitive symptoms (F(2,81) =9.8, p 0.001). Neuroinflammation was significantly higher in CMI compared CON both pre- and post-exercise; and occurred diffusely across the brain. No specific brain regions were differentially impacted by exercise in either CMI nor CON with small effect size differences for all regions tested.Conclusions: Long COVID report similar impacts on their health and functioning, as well as a similar PEM experience as ME/CFS when tested experimentally. Widespread neuroinflammation is present in CMI, but does not appear to be affected 24 hours post-exercise. Future studies should incorporate both peripheral and central measures of inflammation to evaluate potential exaggeration of peripheral immune responses and their correlation with central nervous system inflammation. Larger cohorts with broader ranges of illness severity and duration are essential to generalizability.
일반주제명  
Neurosciences
일반주제명  
Health sciences
일반주제명  
Psychobiology
일반주제명  
Medical imaging
일반주제명  
Kinesiology
키워드  
Chronic illness
키워드  
Exercise
키워드  
Fatigue
키워드  
Neuroimaging
기타저자  
The University of Wisconsin - Madison Kinesiology
기본자료저록  
Dissertations Abstracts International. 87-02B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aNinneman,  Jacob  V.
■24510▼aThe  Role  of  Neuroinflammation  in  Post-Exertional  Malaise  Among  Chronic  Multisymptom  Illness
■260    ▼a[Sl]▼bThe  University  of  Wisconsin  -  Madison▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a210  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-02,  Section:  B.
■500    ▼aAdvisor:  Cook,  Dane  B.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Wisconsin  -  Madison,  2025.
■520    ▼aIntroduction:  Chronic  Multisymptom  Illnesses  (CMIs)  (e.g.,  Long  COVID,  Myalgic  Encephalomyelitis/Chronic  Fatigue  Syndrome  (ME/CFS),  and  Gulf  War  Illness  (GWI))  are  characterized  by  chronic  fatigue,  pain,  and  neurocognitive  complaints  without  a  clear  underlying  pathology.  Instead  of  experiencing  the  salubrious  response  typically  associated  with  exercise,  those  with  CMI  experience  a  worsening  of  symptoms  post-exercise,  termed  post-exertional  malaise  (PEM).  Physiology  at  rest  has  not  adequately  explained  CMI  symptoms;  therefore  experimental  models  of  PEM  are  used  to  better  understand  both  disease  pathophysiology  and  symptom  worsening.  The  limited  evidence  available  suggests  that  exercise  can  stimulate  peripheral  inflammation  in  CMI,  although  the  data  are  mixed.  It  is  unknown  whether  exercise  induce  central  nervous  system  inflammation  (i.e.  neuroinflammation).Purpose:  To  investigate  neuroinflammation  at  rest  and  in  response  to  an  acute  exercise  challenge  in  CMI.Methods:  14  CMI  (6  Long  COVID,  6  ME/CFS,  and  2  GWI)  and  14  age  and  sex  matched  controls  (CON)  were  recruited.  Inclusion  criteria  consisted  of  meeting  the  World  Health  Organization  criteria  for  Long  COVID,  the  Canadian  Consensus  Criteria  for  ME/CFS,  and  the  Kansas  Case  definition  for  GWI.  Positron  emission  tomography  (PET)  imaging  and  symptom  measurement,  took  place  one  week  prior  to  and  24  hours  following  a  standardized  exercise  test.  Additionally,  symptoms  measurement  occurred  for  one  week  post  exercise.  PET  imaging  consisted  of  a  70  minute  dynamic  scan  with  a  third  generation  translocator  protein  radiotracer  -  11C-ER176.  Exercise  consisted  of  30  minutes  of  moderate  intensity  cycling  (70%  Heart  Rate  Reserve)  with  continuous  collection  of  the  cardiometabolic  response  with  a  Parvo  metabolic  cart.  All  PET  images  were  normalized  to  a  standardized  space  and  corrected  for  the  injected  dose  and  whole  brain  binding.  Groups  were  compared  at  baseline  and  post-exercise  with  an  analysis  of  covariance  (ANCOVA)  controlling  for  genotype  or  genotype  and  age  and  sex.  A  repeated  measures  ANCOVA  controlling  for  either  genotype  or  genotype,  age,  and  sex  was  used  to  compare  the  response  to  exercise  between  CMI  and  CON.  Relationships  with  symptoms  were  tested  with  multiple  linear  regressions.Results:  As  expected,  CMI  reported  worse  fatigue,  pain,  mental  and  physical  functioning,  sleep,  mood,  as  well  as  lower  levels  of  physical  activity  relative  to  CON.  CMI  and  CON  were  able  to  maintain  their  prescribed  intensity  for  a  similar  percentage  of  the  test  (CMI:  83.5%,  CON:  90.1,  p  =  0.17).  Cardiometabolic  and  perceptual  responses  were  similar  with  only  average  fatigue  being  significantly  different  between  groups.  Significant  group  x  time  interactions  were  identified  for  fatigue  (F(2,81)  =  6.38,  p  =  0.003),  pain  (F(2,81)  =6.06,  p  =  0.004),  and  neurocognitive  symptoms  (F(2,81)  =9.8,  p    0.001).  Neuroinflammation  was  significantly  higher  in  CMI  compared  CON  both  pre-  and  post-exercise;  and  occurred  diffusely  across  the  brain.  No  specific  brain  regions  were  differentially  impacted  by  exercise  in  either  CMI  nor  CON  with  small  effect  size  differences  for  all  regions  tested.Conclusions:  Long  COVID  report  similar  impacts  on  their  health  and  functioning,  as  well  as  a  similar  PEM  experience  as  ME/CFS  when  tested  experimentally.  Widespread  neuroinflammation  is  present  in  CMI,  but  does  not  appear  to  be  affected  24  hours  post-exercise.  Future  studies  should  incorporate  both  peripheral  and  central  measures  of  inflammation  to  evaluate  potential  exaggeration  of  peripheral  immune  responses  and  their  correlation  with  central  nervous  system  inflammation.  Larger  cohorts  with  broader  ranges  of  illness  severity  and  duration  are  essential  to  generalizability.
■590    ▼aSchool  code:  0262.
■650  4▼aNeurosciences
■650  4▼aHealth  sciences
■650  4▼aPsychobiology
■650  4▼aMedical  imaging
■650  4▼aKinesiology
■653    ▼aChronic  illness
■653    ▼aExercise
■653    ▼aFatigue
■653    ▼aNeuroimaging
■690    ▼a0317
■690    ▼a0566
■690    ▼a0349
■690    ▼a0574
■690    ▼a0575
■71020▼aThe  University  of  Wisconsin  -  Madison▼bKinesiology.
■7730  ▼tDissertations  Abstracts  International▼g87-02B.
■790    ▼a0262
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359487▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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