PMID- 23079632
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20211021
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 239
DP  - 2013 Jun 3
TI  - Post-stroke infections exacerbate ischemic brain injury in middle-aged rats: 
      immunomodulation and neuroprotection by progesterone.
PG  - 92-102
LID - S0306-4522(12)01025-1 [pii]
LID - 10.1016/j.neuroscience.2012.10.017 [doi]
AB  - We investigated the effect of delayed, prolonged systemic inflammation on stroke 
      outcomes and progesterone (P4) neuroprotection in middle-aged rats. After 
      transient middle cerebral artery occlusion/reperfusion (MCAO) surgery, rats 
      received P4 (8 or 16 mg/kg) or vehicle injections at 2h, 6h and every 24h until 
      day 7 post-occlusion. At 24h post-injury systemic inflammation was induced by 
      giving three doses of lipopolysaccharide (LPS; 50 mug/kg, at 4h intervals) to 
      model post-stroke infections. We measured serum brain-derived neurotrophic factor 
      (BDNF), pro-inflammatory cytokines, and behavioral parameters at multiple times. 
      Serum BDNF levels decreased more in the vehicle+LPS group compared to 
      vehicle-alone at 3 and 7 days post-injury (P<0.05). Vehicle-alone showed a 
      significant increase in interleukin-1beta, interleukin-6, and tumor necrosis factor 
      alpha levels at different times following stroke and these levels were further 
      elevated in the vehicle+LPS group. P4 at both doses produced a significant 
      (P<0.05) decline in cytokine levels compared to vehicle and vehicle+LPS. P4 
      restored BDNF levels at 3 and 7 days post-stroke (P<0.05). Behavioral assessment 
      (rotarod, grip strength, sensory neglect and locomotor activity tests) at 3, 5 
      and 7 days post-stroke revealed that the vehicle group had significant (P<0.05) 
      deficits in all tests compared to intact controls, and performance was worse in 
      the vehicle+LPS group. P4 at both doses produced significant functional 
      improvement on all tests. Systemic inflammation did not show an additive effect 
      on infarct volume but P4 at both doses showed significant infarct reduction. We 
      suggest that post-stroke infection exacerbates stroke outcomes and P4 exerts 
      neuroprotective/modulatory effects through its systemic anti-inflammatory and 
      BDNF regulatory actions.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Yousuf, S
AU  - Yousuf S
AD  - Department of Emergency Medicine, Brain Research Laboratory, Emory University, 
      Atlanta, GA 30322, USA.
FAU - Atif, F
AU  - Atif F
FAU - Sayeed, I
AU  - Sayeed I
FAU - Wang, J
AU  - Wang J
FAU - Stein, D G
AU  - Stein DG
LA  - eng
GR  - U01 NS062676/NS/NINDS NIH HHS/United States
GR  - U01 NSO 62676/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121016
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Neuroprotective Agents)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/complications/pathology
MH  - Brain-Derived Neurotrophic Factor/analysis/metabolism
MH  - Cytokines/analysis/metabolism
MH  - Inflammation/chemically induced/*complications/pathology
MH  - Lipopolysaccharides/toxicity
MH  - Male
MH  - Neuroprotective Agents/*pharmacology
MH  - Progesterone/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/drug effects
MH  - Stroke/*complications/*pathology
PMC - PMC3586989
MID - NIHMS415178
COIS- DISCLOSURE/CONFLICT OF INTEREST D.G.S. is entitled to royalty payment (~6.5%) 
      from BHR Pharmaceuticals related to research on progesterone and brain injury. 
      His future financial interests may be affected by the outcome of this research. 
      The terms of this arrangement have been reviewed and approved by Emory 
      University, which receives the largest share of any benefits (~60.0%) in 
      accordance with its business practices and conflict of interest policies.
EDAT- 2012/10/20 06:00
MHDA- 2013/10/18 06:00
PMCR- 2014/06/03
CRDT- 2012/10/20 06:00
PHST- 2012/08/03 00:00 [received]
PHST- 2012/09/26 00:00 [revised]
PHST- 2012/10/05 00:00 [accepted]
PHST- 2012/10/20 06:00 [entrez]
PHST- 2012/10/20 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2014/06/03 00:00 [pmc-release]
AID - S0306-4522(12)01025-1 [pii]
AID - 10.1016/j.neuroscience.2012.10.017 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jun 3;239:92-102. doi: 10.1016/j.neuroscience.2012.10.017. 
      Epub 2012 Oct 16.