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EFFECTS OF CHRONIC ETHANOL DRINKING ON THE BLOOD-BRAIN BARRIER AND ENSUING NEURONAL TOXICITY IN ALCOHOL-PREFERRING RATS SUBJECTED TO INTRAPERITONEAL LPS INJECTION.
- Source :
-
Alcohol & Alcoholism . Sep/Oct2007, Vol. 42 Issue 5, p385-399. 15p. 14 Graphs. - Publication Year :
- 2007
-
Abstract
- Aims: Although alcohol drinking impairs the blood-rain barrier (BBB). the underlying mechanism is not fully understood. Thus, the effects of chronic ethanol drinking on the BBB were studied in vivo, Methods: Alcohol-preferring rats were given for 70 days free choice water and 15% ethanol. Then, they received LPS by i.p. injection. Effiux of [144C]sucrose or [14C]dextran was measured by their microinjection into the brain. Endothelial cells and neurons were isolated from the brain and analysed for mitugen-activated protein kinase (MAPK) and the tight-junction (TJ) protein phosphorylation, NFkB activation, mRNA levels of TJ proteins, inducible nitric oxide synthase, tumour necrosis factor α, intuerleukin-1 β (IL-1β) IL-10 CASPASE-8 and DNA damage. Results: LPS transiently increased [14C]sucrose efflux in water drinking, while it caused a lasting increase in [14C]sucrose and [14C]dextran efflux in ethanol-drinking rats. The time-course of changes in the TJ correlated with (i) an increase in extracellular signal-regulated kinase (ERK), p38mapk Jun-N-terminal Kinase (JNK), and TJ protein phosphorylation, (ii) RelA-p50 and p50-p50 activation, and (iii) a decrease in the TJ proteins' mRNA levels in endothelial cells and neurons. Apoptotic cells were detected in water drinking and LPS (WC-LPS) neurons at 24 h after LPS exposure. Neurons from Et-LPS rats did not exhibit apoptosis. Conclusions: LPS injection in WC-LPS rats transiently disrupted the BBB. Lack of JNK activation and CASPASE-8 may be responsible for lack of apoptusis in endothelial cells and vice versa in neurons. Chronic alcohol drinking in ethanol drinking and LPS (Et-LPS) rats augmented and dysregulated the LPS-induced BBB abnormalities but suppressed apoptusis in neurons. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07350414
- Volume :
- 42
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Alcohol & Alcoholism
- Publication Type :
- Academic Journal
- Accession number :
- 27725877
- Full Text :
- https://doi.org/10.1093/alcalc/agl120