PMID- 19066084
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20190917
IS  - 0065-1419 (Print)
IS  - 0065-1419 (Linking)
VI  - 105
DP  - 2008
TI  - Microglial activation and brain injury after intracerebral hemorrhage.
PG  - 59-65
AB  - Microglial activation and thrombin formation contribute to brain injury after 
      intracerebral hemorrhage (ICH). Tumor necrosis factor-alpha (TNF-alpha) and 
      interleukin-1 beta (IL-1beta) are 2 major proinflammatory cytokines. In this 
      study, we investigated whether thrombin stimulates TNF-alpha and IL-1beta 
      secretion in vitro, and whether microglial inhibition reduces ICH-induced brain 
      injury in vivo. There were 2 parts to this study. In the first part, cultured rat 
      microglial cells were treated with vehicle, thrombin (5 and 10U/mL), or thrombin 
      plus tuftsin (0.05 microg/mL), an inhibitor of microglia activation. Levels of 
      TNF-alpha and IL-1beta in culture medium were measured by ELISA at 4, 8, and 24 h 
      after thrombin treatment. In the second part of the study, rats received an 
      intracerebral infusion of 100 microL autologous whole blood with or without 25 
      microg of tuftsin 1-3 fragment. Rats were killed at day 1 or day 3 for 
      immunohistochemistry and brain water content measurement. We found that thrombin 
      receptors were expressed in cultured microglia cells, and TNF-alpha and IL-1beta 
      levels in the culture medium were increased after thrombin treatment. Tuftsin 
      reduced thrombin-induced upregulation of TNF-alpha and IL-1beta. In vivo, 
      microglia were activated after ICH, and intracerebral injection of tuftsin 
      reduced brain edema in the ipsilateral basal ganglia (81.1 +/- 0.7% vs. 82.7 +/- 
      1.3% in vehicle-treated group; p < 0.05) after ICH. These results suggest a 
      critical role of microglia activation in ICH-related brain injury.
FAU - Wu, J
AU  - Wu J
AD  - Medical School, Zhejiang University, Hangzhou, China.
FAU - Yang, S
AU  - Yang S
FAU - Xi, G
AU  - Xi G
FAU - Song, S
AU  - Song S
FAU - Fu, G
AU  - Fu G
FAU - Keep, R F
AU  - Keep RF
FAU - Hua, Y
AU  - Hua Y
LA  - eng
GR  - NS-017760/NS/NINDS NIH HHS/United States
GR  - NS-039866/NS/NINDS NIH HHS/United States
GR  - NS-047245/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Austria
TA  - Acta Neurochir Suppl
JT  - Acta neurochirurgica. Supplement
JID - 100962752
RN  - 0 (CD11b Antigen)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Ions)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.21.5 (Thrombin)
RN  - QF5336J16C (Tuftsin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain Edema/metabolism/pathology
MH  - Brain Injuries/*etiology/*pathology
MH  - CD11b Antigen/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Cerebral Hemorrhage/*complications
MH  - Disease Models, Animal
MH  - Immunologic Factors/pharmacology
MH  - Interleukin-1beta/metabolism
MH  - Ions/metabolism
MH  - Male
MH  - Microglia/drug effects/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thrombin/pharmacology
MH  - Time Factors
MH  - Tuftsin/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2008/12/11 09:00
MHDA- 2009/04/15 09:00
CRDT- 2008/12/11 09:00
PHST- 2008/12/11 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
PHST- 2008/12/11 09:00 [entrez]
AID - 10.1007/978-3-211-09469-3_13 [doi]
PST - ppublish
SO  - Acta Neurochir Suppl. 2008;105:59-65. doi: 10.1007/978-3-211-09469-3_13.