Abstract
Abstract 383: Depletion of Perivascular Macrophages of the Blood-Brain Barrier Reduces Sympathetic Drive in Rats after Myocardial Infarction
Circulation (New York, N.Y.), Vol.118(suppl_18)
10/28/2008
DOI: 10.1161/circ.118.suppl_18.S_295-c
Abstract
Pro-inflammatory cytokines induce cyclooxygenase-2 (COX-2) activity and synthesis of prostaglandin E2 (PGE 2 ) in perivascular macrophages of hypothalamic paraventricular nucleus (PVN). Cytokine-induced PGE 2 synthesis in the brain contributes to increased sympathetic nerve activity following myocardial infarction (MI). Perivascular macrophages can be selectively depleted by clodronate liposomes. Depletion of perivascular macrophages of the blood-brain barrier will reduce COX-2 expression and cytokine-induced sympathetic nerve activity in rats after MI. Clodronate liposomes (CLOD), control liposomes (LIPO) or vehicle (VEH, artificial CSF) were injected (1 μl/min over 40 minutes) into lateral ventricle in rats within 24 hours of MI, or normal rats. One week after injection, perivascular macrophages were completely destroyed and COX-2 immunoreactivity was eliminated in PVN of all CLOD-treated rats but not in LIPO or VEH-treated rats. Activated microglia were unaffected by CLOD. Compared with sham-operated rats (n=10), VEH-treated MI rats (n=11) had increased COX-2 (0.09±0.01* vs 0.05±0.01, normalized to GAPDH, *P<0.05), interleukin-1β (IL-1β, 0.48±0.06* vs 0.21±0.03) and tumor necrosis factor - α (TNF-α, 0.50±0.09* vs 0.22±0.08) mRNA in PVN, IL-1β (23±2* vs 15±1, pg/ml), TNF-α (5±1* vs 2±0, pg/ml), norepinephrine (1146±143* vs 450±66, pg/ml) levels in plasma, PGE 2 (1152±109* vs 480±84, pg/ml) in CSF and Fra-like-positive neurons (40±3* vs 21±2) in PVN. CLOD treatment of MI rats (n=11) normalized COX-2 mRNA in PVN and reduced CSF PGE 2 (by 30%#, #P<0.05 vs VEH), plasma norepinephrine (by 34%#) and Fra-like positive PVN neurons (by 29%#), but had no effects on IL-1β and TNF-αin PVN or plasma. In normal rats, CLOD treatment (n=9) reduced (P<0.05, vs VEH) sympatho-excitatory responses (renal sympathetic nerve activity, blood pressure and heart rate) induced by intracarotid artery injection of TNF-α (0.5 μg/kg). No effects were found in LIPO-treated MI or normal rats. Pro-inflammatory cytokines stimulate sympathetic excitation after MI by inducing COX-2 activity and PGE 2 production in perivascular macrophages of the blood-brain barrier.
Details
- Title: Subtitle
- Abstract 383: Depletion of Perivascular Macrophages of the Blood-Brain Barrier Reduces Sympathetic Drive in Rats after Myocardial Infarction
- Creators
- Yang YuZhi-hua ZhangShun-guang WeiJordi SerratsRobert M WeissRobert B Felder
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.118(suppl_18)
- DOI
- 10.1161/circ.118.suppl_18.S_295-c
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 10/28/2008
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984256800002771
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