Impact of oral contraceptives and smoking on females after traumatic brain injury

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Principal Investigator: Helen M Bramlett
Organization: MIAMI VA HEALTH CARE SYSTEM
Fiscal Year: 2024
Funding agency: Veterans Affairs

Traumatic  brain  injury  (TBI)  is a  leading  cause  of  death and  cognitive  disability and  is  a  known  risk  of  military 
service.  Women  constitute  a  large  share  of  servicemembers  seeking  care  from  the  Veterans  Health 
Administration.  Women  servicemembers,  especially  those  involved  in  recent  conflicts,  smoke  at  significantly 
higher  rates  than  civilian  women.  Along  with  smoking,  women  servicemembers  are  also  likely  to  use  oral 
contraceptives (OC), owing to their reproductive age. However, what impact the simultaneous usage of OC and 
smoking will have on outcome after mild TBI (mTBI) remains to be investigated. Research conducted during the 
last decade in our laboratory demonstrated that simultaneous exposure to smoking derived-­nicotine (N) and OC 
(N+OC)  as  short  as  three  weeks  renders  reproductive-­age  female  rats  more  susceptible  to  secondary  brain 
injury.  N+OC  exposure  impedes  estrogen  receptor  subtype  beta  (ER-­β)-­mediated  mitochondrial  function  by 
interfering with electron transport chain complex IV (CIV) activity and increases inflammasome activation in the 
brain.  The  current  study  aims  to  test  whether  observed  loss  of  ER-­β-­mediated  CIV  activity,  induction  of 
inflammation,  and  subsequent  stress  on  brain  energy  metabolism  due  to  N+OC  exposure  leads  to  worsened 
post-­mTBI secondary brain injury and cognitive decline. Cognitive decline is one of the major consequences of 
mTBI  and  what  effects  the  combination  of  N+OC  has  on  post-­mTBI  cognition  needs  investigation.  Pilot  data 
showing that nicotine itself or  nicotine-­containing electronic cigarette (EC) exposure combined with OC results 
in  deleterious effects on cognitive  capacities  including spatial  learning and  memory  in  female  rats  leads  us to 
test  in  this  study  whether  post-­TBI  declines  in  cognition  are  made  even  worse  by  N/EC+OC  exposure.  The 
successful  completion  of  proposed  study  will  characterize  the  effects  of  N+OC  on  mTBI-­induced 
neurodegeneration and cognitive decline and will fill a current gap in knowledge on secondary brain injury after 
mTBI in women. 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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