PMID- 16641452
OWN - NLM
STAT- MEDLINE
DCOM- 20060609
LR  - 20211020
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 50
IP  - 5
DP  - 2006 May
TI  - Minocycline impedes African trypanosome invasion of the brain in a murine model.
PG  - 1798-804
AB  - Passage of Trypanosoma brucei across the blood-brain barrier (BBB) is a hallmark 
      of late-stage human African trypanosomiasis. In the present study we found that 
      daily administration of minocycline, a tetracycline antibiotic, impedes the 
      penetration of leukocytes and trypanosomes into the brain parenchyma of T. brucei 
      brucei-infected C57BL/6 mice. The trypanosome-induced astrocytic and microglial 
      reactions were reduced in the minocycline-treated mice, as were the levels in the 
      brain of transcripts encoding adhesion molecules intercellular adhesion molecule 
      1 (ICAM-1) and endothelial-leukocyte adhesion molecule 1 (E-selectin); the 
      inflammatory cytokines tumor necrosis factor alpha, interleukin-1alpha 
      (IL-1alpha), IL-1beta, IL-6, and gamma interferon; and matrix metalloprotease 3 
      (MMP-3), MMP-8, and MMP-12. Loss of weight occurring during infection with T. b. 
      brucei was not observed after treatment of the mice with minocycline; these mice 
      also survived longer than nontreated mice. Invasion of trypanosomes and 
      leukocytes into the brain parenchyma most likely triggered the loss of weight and 
      death of infected animals, since minocycline did not affect the growth of T. b. 
      brucei either in vitro or in vivo or the levels of the transcripts encoding the 
      cytokines and MMPs in the spleen. In conclusion, our data show that T. b. brucei 
      invasion of the brain is related to that of leukocytes and that minocycline can 
      ameliorate the disease in trypanosome-infected mice.
FAU - Masocha, Willias
AU  - Masocha W
AD  - Department of Neuroscience, Retzius vag 8, Karolinska Institutet, SE-171 77 
      Stockholm, Sweden. willias.masocha@ki.se
FAU - Rottenberg, Martin E
AU  - Rottenberg ME
FAU - Kristensson, Krister
AU  - Kristensson K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cytokines)
RN  - 0 (E-Selectin)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Blood-Brain Barrier/cytology/*parasitology
MH  - Cytokines/metabolism
MH  - *Disease Models, Animal
MH  - E-Selectin/metabolism
MH  - Immunohistochemistry
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Minocycline/*pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Trypanosoma brucei brucei/*physiology
PMC - PMC1472198
EDAT- 2006/04/28 09:00
MHDA- 2006/06/10 09:00
PMCR- 2006/09/01
CRDT- 2006/04/28 09:00
PHST- 2006/04/28 09:00 [pubmed]
PHST- 2006/06/10 09:00 [medline]
PHST- 2006/04/28 09:00 [entrez]
PHST- 2006/09/01 00:00 [pmc-release]
AID - 50/5/1798 [pii]
AID - 1338-05 [pii]
AID - 10.1128/AAC.50.5.1798-1804.2006 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2006 May;50(5):1798-804. doi: 
      10.1128/AAC.50.5.1798-1804.2006.