Traditionally regarded as an “immune-privileged” organ, the brain is now known to harbor two complementary macrophage systems that jointly maintain neural homeostasis and drive disease progression.
The first population consists of microglia. Seeded from the yolk sac during embryogenesis and self-renewing throughout life, they are the most abundant innate immune cells in the parenchyma. By pruning synapses, clearing cellular debris and sensing metabolic changes, microglia regulate neuronal plasticity and blood–brain-barrier integrity.
The second population is the border-associated macrophages (BAMs)—meningeal, perivascular and choroid-plexus macrophages—that are continuously replenished by bone-marrow-derived monocytes after birth. Positioned at the blood–brain interfaces, BAMs survey pathogens, maintain cerebro-spinal-fluid immune surveillance and modulate vascular permeability. Under pathological conditions such as Alzheimer’s disease, cerebral ischemia or brain tumors, additional peripheral monocytes infiltrate the CNS and differentiate into disease-associated macrophages (DAM or TAM). These cells can either cooperate with or oppose microglia, amplifying neuro-inflammation, promoting plaque clearance or supporting the tumor micro-environment. Thus, the brain–macrophage axis acts as both a gatekeeper of neural protection and a key therapeutic target in neuro-degeneration and brain-tumor immunotherapy.
In previous lessons we described how clodronate liposomes deplete macrophages in liver, lung and gut. Today we review publications and protocols that use clodronate liposomes to eliminate brain macrophages.
Literature 1
Article Source: Characteristics of activation of monocyte-derived macrophages versus microglia after mouse experimental intracerebral hemorrhage (IF=4.5,Q1)
Macrophage Clearance Methods:
2- to 4-month-old male Tmem119-EGFP mice (C57BL/6-Tmem119em2Gfng/J) received an intracerebral injection of 30 µL autologous blood mixed with 5 µL clodronate or control liposomes. Animals were euthanized on day 3 (n = 6 per group).
Results are shared:
To test whether infiltrating monocyte-derived macrophages (MDMs) and microglia were phagocytically active, clodronate liposomes were co-injected with blood to trigger death of liposome-engulfing phagocytes. Three days post-ICH, clodronate-treated mice showed near-complete loss of MDMs in the hematoma core (0 (0, 8) vs 18 (10, 22) cells/mm² in controls, p = 0.0346), a 77 % reduction in peri-hematomal MDMs (33 (18, 62) vs 142 (111, 170) cells/mm², p = 0.0108), and almost complete depletion in the ipsilateral basal ganglia (0 (0, 13) vs 8 (6, 24) cells/mm², p > 0.05).
Literature 2
Article Source: CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain (IF=13.3,Q1)
Macrophage Clearance Methods:
Clodronate liposomes (15 mL/kg) or PBS were injected i.v. via the tail vein one day before and three days after sham or spared-nerve-injury (SNI) surgery. Efficiency was verified by flow cytometry of peripheral blood and by hippocampal immunofluorescence in naïve mice.
Results are shared:
Eighteen hours after the first injection, flow cytometry and brain immunofluorescence confirmed robust monocyte depletion. On post-operative day 9, short-term memory was assessed by novel-object-recognition test (NORT). As expected, clodronate eliminated the vast majority of classical (CD11b⁺Ly6C^high^) and non-classical (CD11b⁺Ly6C⁻) monocytes without affecting lymphocyte subsets such as NK cells or neutrophils.
Literature 3
Article Source: B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells (IF=10.1,Q1)
Macrophage Clearance Methods:
8- to 12-week-old male C57Bl/6J mice received 10 µL g⁻¹ body weight clodronate liposomes i.v.; controls received the same volume of PBS liposomes. Depletion was verified by flow cytometry in multiple organs.
Results are shared:
Intravenous clodronate selectively eliminated highly phagocytic CD45hiCD11bhi monocytes/macrophages, reducing their infiltration into the injured brain by ~90 % at 48 h post-controlled-cortical-impact (CCI).
Literature 4
Article Source: Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury (IF=10.1,Q1)
Macrophage Clearance Methods:
Mice were injected i.v. with 200 µL clodronate liposomes (Cl-LPM), PBS liposomes (Control-LPM) or Dil-labeled liposomes (Dil-LPM) at 4 and 1 days before CCI or sham surgery. Dil uptake was quantified on blood smears by fluorescence microscopy.
Results are shared:
In both sham and CCI mice, Cl-LPM reduced the CD45⁺/CD11b⁺/Ly6G⁻/CD115⁻ compartment by ~40 %. Within this gate, CD115⁺ monocytes dropped from 33.8 ± 4.3 % in PBS-LPM controls to 5.5 ± 0.5 %, and their absolute numbers were comparably decreased.
Product Recommendation
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Product name |
Item number |
Specification |
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40337ES08 |
5 mL |
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40337ES10 |
10 mL |
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40338ES08 |
5 mL |
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40338ES10 |
10 mL |
We provides a complete reagent portfolio for macrophage research—from cell isolation, in-vitro generation, and depletion-model construction to functional validation—helping you generate high-impact publications.Please visit the Yeasen’s website.