Perivascular Macrophages Mediate Microvasospasms After Experimental Subarachnoid Hemorrhage

Lin, Xiangjiang; Khalin, Igor; Harapan, Biyan Nathanael; Terpolilli, Nicole A.; Schwarting, Julian; Plesnila, Nikolaus

doi:10.1161/strokeaha.122.042290

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…Another postulated mechanism involves anti-inflammatory properties of milrinone through inhibition of cytokines production 35 , since inflammation is also suspected to play a role in DCI development 53 . For instance, perivascular macrophage have been shown to participate in microvascular spasms in experimental models, and could therefore be a cellular target for milrinone non-vascular effects 54 .…”

Section: Discussionmentioning

confidence: 99%

CT perfusion-guided administration of IV milrinone is associated with a reduction in delayed cerebral infarction after subarachnoid hemorrhage

Szabo,

Baccialone,

Kucharczak

et al. 2024

Sci Rep

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Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The $${\text{"before"}}$$ "before" period included 277 patients, and the $${\text{"after"}}$$ "after" one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the $${\text{"after"}}$$ "after" period. Conversely, the occurrence of DCIn was reduced with the $${\text{"after"}}$$ "after" management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, $$p=0.001$$ p = 0.001 ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, $$p<0.001$$ p < 0.001 ) and associated with superior hemodynamics. The present study from a large cohort of aSAH patients suggests, for one part, the interest of CTP in early diagnosis of vasospasm and DCI, and for the other the efficacy of CT perfusion-guided systemic administration of milrinone in both preventing and treating DCIn.

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Section: Discussionmentioning

confidence: 99%

CT perfusion-guided administration of IV milrinone is associated with a reduction in delayed cerebral infarction after subarachnoid hemorrhage

Szabo,

Baccialone,

Kucharczak

et al. 2024

Sci Rep

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“…To this end, we used clodronate liposomes (CLO) as a reagent to deplete PVM. Depletion of PVM by CLO injection into the CSF via the cisterna magna is a well-established method (Drieu et al, 2022;Lin et al, 2023); CLO are phagocytosed by macrophages and induce their apoptotic cell death (Van Rooijen et al, 1996). Compared to control liposomes (encapsulated PBS), CLO injection induced depletion of PVM in the lumbar spinal cord at 3 and 7 days after injection, but the number of PVM was restored at 14 days after injection (Figures 3A, B).…”

Section: Repetitive Intracisternal Injection Of Clodronate Liposomes ...mentioning

confidence: 96%

Depletion of perivascular macrophages delays ALS disease progression by ameliorating blood-spinal cord barrier impairment in SOD1G93A mice

Adachi,

Miyata,

Chida

et al. 2023

Front. Cell. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which non-cell-autonomous processes have been proposed as its cause. Non-neuronal cells that constitute the environment around motor neurons are known to mediate the pathogenesis of ALS. Perivascular macrophages (PVM) are immune cells that reside between the blood vessels of the central nervous system and the brain parenchyma; PVM are components of the neurovascular unit and regulate the integrity of the blood-spinal cord barrier (BSCB). However, it is not known whether regulation of BSCB function by PVM is involved in the pathogenesis of ALS. Here, we used SOD1G93A mice to investigate whether PVM is involved in the pathogenesis of ALS. Immunostaining revealed that the number of PVM was increased during the disease progression of ALS in the spinal cord. We also found that both anti-inflammatory Lyve1+ PVM and pro-inflammatory MHCII+ PVM subtypes were increased in SOD1G93A mice, and that subtype heterogeneity was shifted toward MHCII+ PVM compared to wild-type (WT) mice. Then we depleted PVM selectively and continuously in SOD1G93A mice by repeated injection of clodronate liposomes into the cerebrospinal fluid and assessed motor neuron number, neurological score, and survival. Results showed that PVM depletion prevented the loss of motoneurons, slowed disease progression, and prolonged survival. Further histological analysis showed that PVM depletion prevents BSCB collapse by ameliorating the reduction of extracellular matrix proteins necessary for the maintenance of barrier function. These results indicate that PVM are involved in the pathogenesis of ALS, as PVM degrades the extracellular matrix and reduces BSCB function, which may affect motor neuron loss and disease progression. Targeting PVM interventions may represent a novel ALS therapeutic strategy.

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“…In this disease context, the interaction of endothelial cells and PvMΦ impaired the BBB and resulted in vascular dysfunction, leading to cognitive deficits in chronic hypertension [ 31 ]. Other studies in experimental subarachnoid haemorrhage showed that intracerebroventricular injected clodronate liposomes depleted PvMΦ and delayed blood clearance but had a beneficial effect on neuronal cell death, neuroinflammation, neurological impairment, and microvasospasms [ 68 , 123 ]. These studies show that PvMΦ effects on BBB function are variable, which may be related to either the experimental set-ups/model investigated or potentially the heterogeneity of PvMΦ in different locations, at different developmental stages or under different metabolic conditions.…”

Section: Microglia and Perivascular Macrophages (Pvmφ) Control Bbb Pe...mentioning

confidence: 99%

Endothelial cells and macrophages as allies in the healthy and diseased brain

Denes,

Hansen,

Oezorhan

et al. 2024

Acta Neuropathol

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Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells and macrophages are key cellular players that mediate pathology in many CNS diseases. Macrophages in the brain consist of the CNS-associated macrophages (CAMs) [also referred to as border-associated macrophages (BAMs)] and microglia, both of which are close neighbours or even form direct contacts with endothelial cells in microvessels. Recent progress has revealed that different macrophage populations in the CNS and a subset of brain endothelial cells are derived from the same erythromyeloid progenitor cells. Macrophages and endothelial cells share several common features in their life cycle—from invasion into the CNS early during embryonic development and proliferation in the CNS, to their demise. In adults, microglia and CAMs have been implicated in regulating the patency and diameter of vessels, blood flow, the tightness of the blood–brain barrier, the removal of vascular calcification, and the life-time of brain endothelial cells. Conversely, CNS endothelial cells may affect the polarization and activation state of myeloid populations. The molecular mechanisms governing the pas de deux of brain macrophages and endothelial cells are beginning to be deciphered and will be reviewed here.

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Perivascular Macrophages Mediate Microvasospasms After Experimental Subarachnoid Hemorrhage

Cited by 9 publications

References 30 publications

CT perfusion-guided administration of IV milrinone is associated with a reduction in delayed cerebral infarction after subarachnoid hemorrhage

CT perfusion-guided administration of IV milrinone is associated with a reduction in delayed cerebral infarction after subarachnoid hemorrhage

Depletion of perivascular macrophages delays ALS disease progression by ameliorating blood-spinal cord barrier impairment in SOD1G93A mice

Endothelial cells and macrophages as allies in the healthy and diseased brain

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