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Publications Citing Intracerbroventrivular (ICV) Administration into the CSF

Publications Citing Intracerbroventrivular (ICV) Administration into the CSF

Ref No. Animal Description Volume Dosed (Site) Clodronate Concentration Lipid Composition Lipid Mole % Liposome Type
18 C57BL/6J mice, female, 4-6 wks 8 µl X2 (lateral ventricles) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
19 Lewis rats,male,200-250 g 50 µl (4th ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
20 CL4 mice 8 µl (lateral ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
21 Wistar rats,male,adult 15 µl (right lateral ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
22 Sprague Dawley rats,male,260-340 g 50 µl (“a” lateral ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
23 Sprague Dawley rats,male,260-340 g 50 µl (“a” lateral ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
24 Sprague Dawley rats,male,250-300 g 40 µl (4th ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
25 ?, male,200-250 g 50 µl (4th ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV
26 C57BL/6,male,8 wks 10 µl (? lateral ventricle) 5 mg/ml EPC:Chol: Aminophenyl mannose 69/21/10 MLV

18. I. Galea; K. Palin; T.A. Newman; N.Van Rooijen; V.H. Perry; D. Boche, Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain, Glia, 49(2005) 375-384.

Local cell types targeted included MR+ meningeal macrophages (MM), MR+ perivascular macrophages (PVM) and MR+ choroid plexus macrophages (CPM). The systematic depletion method was intraventricular and no systematic depletion result was mild with temporal depletion in the liver and spleen.

Summary: MR+ cells (PVM, MM, CPM) are identified and depleted in several experimental models of inflammation. Although the liposomes are described as “mannosylated”, it is unlikely that these liposomes displayed mannose on their surface in such a way that binding to the MR occurred. This will be discussed in detail elsewhere.

19. T.A. Newman; I. Galea; N. van Rooijen; V.H. Perry, Blood-derived dendritic cells in an acute brain injury, J. Neuroimmunol., 166(2005) 167-172.

Local cell types targeted included ED+2 menigeal macrophages and ED+2 perivascular macrophages. The systematic depletion method was intraventricular with mild results and temporal depletion in the liver and spleen.

Summary: Ox62+ DC from the blood are recruited to the site of kainic acid-induced acute inflammation in the brain. Depletion of the PVM and MM does not prevent this migration but does appear to attenuate the response.

20. I. Galea; M. Bernardes-Silva; P.A. Forse; N. van Rooijen; R.S. Liblau; V.H. Perry, An antigen-spcific pathway for CD8T cells across the blood-brain barrier, Journal of Experimental Medicine, 204(2007) 2023-2030.

Local cell types targeted include MR+ perivascular macrophages. There was no systematic method of depletion and therefore no systematic depletion result.

Summary: While PVM have previously been identified as the primary ant.igen presenting cells in the brain, their depletion does not reduce the recruitment of CD8+T cells in response to MHC I expression by cerebral endothelium.

21. I. Galea; L.M. Felton; S. Waters; N. van Rooijen; V.H. Perry; T.A. Newman, Immune-to-brain signalling: The role of cerebral CD163-positive macrophages, Neuroscience Letters 448(2008) 41-46.

Local cell types targeted include CD163+ macrophages. The systematic depletion method was intraventricular with mild results and temporal depletion in the liver and spleen.

Summary: This paper highlights the importance if the selection of the dose and the injection site in selectively depleting brain macrophages without compromising systematic macrophages. They demonstrate the ICV liposomes can leave the brain through the lymphatic system as well as the blood. Depletion of CC163+ macrophages did not reduce the brain inflammatory response to systematically dosed LPS.

22. J. Serrats; P.E. Sawchenko, How T-cell-dependent and-independent challenges access the brain: vascular and neural response to bacterial lipopolysaccharide and staphylococcal enterotoxin B, Brain, Behavior, and Immunity, 23(2009) 1038-1052.

Local cell types targeted include ED+2 perivascular macrophages. There was no systematic method of depletion and therefore no systematic depletion results.

Summary: PVM are identified as central mediators in the inflammatory response to LSP and SEB, although the response the the two different stimuli are not identical.

23. B. Garcia-Bueno; J. Serrats; P.E. Sawchenko, Cerebrovascular Cyclooxygenase-1 Expression, Regulation, and Role in Hypothalamic-Pituitary-Adrenal Axis Activation by Inflammation Stimuli, Journal of Neuroscience, 29(2009) 12970-12981.

Local cell types targeted include CD163+ perivascular macrophages. There was no systematic depletion and therefore no systematic depletion results.

Summary: Depletion COX1+ PVM significantly down-regulated the inflammatory response of the CNS endothelial cells, therefore manipulation of PVM may be utilized in anti-inflammatory therapies.

24. J. Serrata; J.C. Schiltz; B. Garcia-Bueno; N. van Rooijen; T.M. Reyes; P.E. Sawchenko, Dual Roles for Perivascular Macrophages in Immune-to-Brain Signaling, Neuron, 65(2010) 94-106.

Local cell types targeted include ED+2 perivascular macrophages. The systematic depletion method was intraventricular with no depletion in the liver at 5-7 days.

Summary: Depletion of PVM increases the inflammatory response of the endothelial cells to LSP challenge, indicating an anti-inflammatory role for PVM. However, IL-1 provoked prostaglandin production by PVM thus sending a pro-inflammatory signal to the HPA axis.

25. Y. Yu; Z.H. Zhang; S.G. Wei; J. Serrats; R.M. Weiss; R.B. Felder, Brian Perivascular Macrophages and the Sympathetic Response to inflammation in Rats After Myocardial Infarction, Hyertension, 55(2010) 652-659.

Local cell types targeted include COX-2+ perivascular macrophages. The systematic depletion method was intraventricular with mild results and temporal depletion in the liver and spleen.

Summary: When COX-2+ perivascular macrophages are depleted in the paraventricular nucleus post-induction of myocardial infarction (MI), the production of PGE2 is also inhibited. This results in decreased syspathetic ecitation when compared to empty liposomes treated or sham-treated rats suggesting that preivascular macrophage COX-2+ activity is at least partially responsible for increased sympathetic activity post-MI.

26. M.D. Carmichael; J.M. Davis; E.A. Murphy; J.A. Carson; N. van Rooijen; E. Mayer; A. Ghaffar, Role of brain macrophages on IL-1β and fatigue following eccentric exercise-induced muscle damage, Brain, Behavior, Immunity, 24(2010) 564-568.

Local cell types targeted included ED+2 menigeal macrophages and ED+2 perivascular macrophages. There was no systematic depletion method and therefore no systematic depletion results.

Summary: Depletion of PVM and MM decreased the level of IL-1β which had been induced by exercise. The reduction of IL-1β correlated to reduced fatigue and muscle damage post-exercise.

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