title: Recombinant tissue plasminogen activator promotes, and progesterone attenuates, microglia/macrophage M1 polarization and recruitment of microglia after MCAO stroke in rats.
abstract: BACKGROUND
  Tissue plasminogen activator (tPA) is one of the few approved treatments for stroke, but its effects on the phenotype of microglia/macrophages are poorly understood. One of its side effects is an increase in the inflammatory response leading to neuronal cell damage and death in the ischemic cascade after stroke. Injury-induced activated microglia/macrophages can have dual functions as pro-inflammatory (M1) and anti-inflammatory (M2) factors in brain injury and repair. Recent studies show that progesterone (PROG) is a potent anti-inflammatory agent which affects microglia/macrophage expression after brain injury.
  
  
  OBJECTIVE
  We examined the interaction of tPA-induced expression of microglia/macrophage phenotypes and PROG's anti-inflammatory effects.
  
  
  RESULTS
  tPA treatment increased the recruitment of microglia/macrophages, the polarity of M1 reactions, the expression of MIP-1α in neurons and capillaries, and the expression of MMP-3 compared to vehicle, and PROG modulated these effects.
  
  
  CONCLUSIONS
  PROG treatment attenuates tPA-induced inflammatory alterations in brain capillaries and microglia/macrophages both in vivo and in vitro and thus may be a useful adjunct therapy when tPA is given for stroke.
authors.affiliation: Department of Emergency Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Soonmi
authors.initials: S
authors.lastname: Won
authors.affiliation: Department of Physiology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: dstei04@emory.edu.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016764:Cell Polarity / Q000187:drug effects; D054405:Chemokine CCL3 / Q000378:metabolism; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D011994:Recombinant Proteins; D011374:Progesterone; D010959:Tissue Plasminogen Activator; D019278:Matrix Metalloproteinase 3
keywords: M1/M2 polarization; MIP-1α; Macrophage; Microglia; Neuroinflammation; Progesterone; Recovery; Stroke; tPA