The evolving roles of pericyte in early brain injury after subarachnoid hemorrhage

Chen, Yujie; Li, Qiang; Tang, Jiping; Feng, Hua; Zhang, Junyi

doi:10.1016/j.brainres.2015.05.004

Cited by 29 publications

(23 citation statements)

References 174 publications

(190 reference statements)

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“…As microvessels lack smooth muscle, blood flow is frequently assumed to be regulated by precapillary arterioles. However, the majority (65%) of adrenergic innervation of central nervous system (CNS) blood vessels terminates near microvessels rather than arterioles, and in the muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in microvessels ( 4 , 5 , 7 ). Pericytes in CNS microvessels contain contractile proteins and can initiate such signaling ( 29 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…An explanation for these results could be that cerebral microcirculation and its regulatory mechanisms are directly affected by SAH ( 4 ), particularly pericytes, the primary cell type controlling microcirculation in brain parenchyma ( 5 ). A number of studies have addressed the role of microcirculatory dysfunction during SAH, where arteriolar constriction is typically observed ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

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Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

Cui

et al. 2016

Experimental and Therapeutic Medicine

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Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

Cui

et al. 2016

Experimental and Therapeutic Medicine

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“…Germinal matrix hemorrhage (GMH) is a common cerebrovascular event that affects up to 20% of premature infants, and leads to severe long-term neurological and cognitive deficits, including cerebral palsy and mental retardation (Ballabh, 2014). After the hemorrhage occurs, the damage of brain tissue is amplified by the activation of inflammatory cascades, which are responsible for the further neurodegeneration (Brown and Neher, 2010; Chen et al, 2015; Tao et al, 2016; Zhou et al, 2014). Given the extended inflammation-induced tissue destruction, the suppression of inflammatory response could be a particularly important intervention to limit GMH-induced brain injury.…”

Section: Introductionmentioning

confidence: 99%

Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2/AMPK/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats

Zhang

Ding

et al. 2018

Brain, Behavior, and Immunity

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Chemerin, an adipokine, has been reported to reduce the production of pro-inflammatory cytokines and neutrophil infiltration. This study investigated the role of Chemerin and its natural receptor, ChemR23, as well as its downstream mediator calmodulin-dependent protein kinase kinase 2 (CAMKK2)/adenosine monophosphate-activated protein kinase (AMPK) /Nuclear factor erythroid 2-related factor 2 (Nrf2) following germinal matrix hemorrhage (GMH) in neonatal rats, with a specific focus on inflammation. GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U) in P7 rat pups. The results demonstrated that human recombinant Chemerin (rh-Chemerin) improved neurological and morphological outcomes after GMH. Rh-Chemerin promoted accumulation and proliferation of M2 microglia in periventricular regions at 72 h. Rh-Chemerin increased phosphorylation of CAMKK2, AMPK and expression of Nrf2, and decreased IL-1beta, IL-6 and TNF-alpha levels. Selective inhibition of ChemR23/CAMKK2/AMPK signaling in microglia via intracerebroventricular delivery of liposome-encapsulated specific ChemR23 (Lipo-alpha-NETA), CAMKK2 (Lipo-STO-609) and AMPK (Lipo-Dorsomorphin) inhibitor increased the expression levels of IL-1beta, IL-6 and TNF- alpha, demonstrating that ChemR23/CAMKK2/AMPK signaling in microglia suppressed inflammatory response after GMH. Cumulatively, these data showed that rh-Chemerin ameliorated GMH-induced inflammatory response by promoting ChemR23/CAMKK2/AMPK/Nrf2 pathway, and M2 microglia may be a major mediator of this effect. Thus, rh-Chemerin can serve as a potential agent to reduce the inflammatory response following GMH.

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“…In our experiments, we knocked out retention motif of PDGF-B, which is the binding site of PDGF-B with the extracellular matrix [16]. Previous studies demonstrated that PDGF-B ret/ret mice suffered cerebral vascular dysfunction by pericyte recruitment deficiency and subsequent breach on the blood-brain barrier after SAH [4,[17][18][19][20]. Similarly, the pericytes were covered with 26-40% microvessels in mature lungs [21], which might also be regulated by PDGF-B in the pathophysiological progression after SAH to cause pulmonary edema, previously considered to be neurogenic [22].…”

Section: Discussionmentioning

confidence: 99%

Aggravated pulmonary injury after subarachnoid hemorrhage in PDGF-Bret/ret mice

Pan

et al. 2020

Chin Neurosurg Jl

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Background: Recent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage (SAH). However, pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes. Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks, we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH. Methods: In our experiments, platelet-derived growth factor B (PDGF-B) retention motif knockout (PDGF-B ret/ret) mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression. Neurological score, SAH grade, hematoxylin-eosin staining, and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery, as well as western blotting and immunofluorescence staining for underlying molecular expressions. Results: We found that neonatal PDGF-B ret/ret mice exhibited pulmonary atelectasis 12 h after birth. Further investigation showed a decrease in PaO 2 /FiO 2 and lung-specific surfactant proteins in adult PDGF-B ret/ret mice. These dysfunctions were much worse than those in wild-type mice at 24 h after SAH. PDGF-B overexpression alleviated pulmonary dysfunction after SAH. Conclusions: These results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH. Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.

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The evolving roles of pericyte in early brain injury after subarachnoid hemorrhage

Cited by 29 publications

References 174 publications

Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2/AMPK/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats

Aggravated pulmonary injury after subarachnoid hemorrhage in PDGF-Bret/ret mice

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