Platelet derived growth factor and subarachnoid haemorrage: A study on cisternal cerebrospinal fluid

Gaetani, Paolo; Tancioni, Flavio; Grignani, G; Tartara, Fulvio; Merlo, E; Brocchieri, Alessandra; Baena, Riccardo Rodriguez y

doi:10.1007/bf01808827

Cited by 36 publications

(22 citation statements)

References 30 publications

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“…They are involved in a wide range of biochemical processes, including mitosis, would healing, vessel formation, and vasoconstriction. [25][26][27] Previously, PDGF levels and outcomes after aSAH have been reported 28,29 ; however, our findings pertaining to interactions between PDGFs, CCL5, sCD40L, 30 and CXCL1P1 are previously undescribed and warrant further investigation. (2) IL-2, IL-9, IL-12p40, and TNF-b cytokines: From T 1 to T 4 , a cluster including IL-2, IL-12p40, TNF-b, and IL-9 was observed.…”

mentioning

confidence: 68%

Systematic model of peripheral inflammation after subarachnoid hemorrhage

Savarraj¹,

Parsha²,

Hergenroeder³

et al. 2017

Neurology

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Objective: To investigate inflammatory processes after aneurysmal subarachnoid hemorrhage (aSAH) with network models.Methods: This is a retrospective observational study of serum samples from 45 participants with aSAH analyzed at multiple predetermined time points: ,24 hours, 24 to 48 hours, 3 to 5 days, and 6 to 8 days after aSAH. Concentrations of cytokines were measured with a 41-plex human immunoassay kit, and the Pearson correlation coefficients between all possible cytokine pairs were computed. Systematic network models were constructed on the basis of correlations between cytokine pairs for all participants and across injury severity. Trends of individual cytokines and correlations between them were examined simultaneously.Results: Network models revealed that systematic inflammatory activity peaks at 24 to 48 hours after the bleed. Individual cytokine levels changed significantly over time, exhibiting increasing, decreasing, and peaking trends. Platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, soluble CD40 ligand, and tumor necrosis factor-a (TNF-a) increased over time. Colony-stimulating factor (CSF) 3, interleukin (IL)-13, and FMS-like tyrosine kinase 3 ligand decreased over time. IL-6, IL-5, and IL-15 peaked and decreased. Some cytokines with insignificant trends show high correlations with other cytokines and vice versa. Many correlated cytokine clusters, including a plateletderived factor cluster and an endothelial growth factor cluster, were observed at all times. Participants with higher clinical severity at admission had elevated levels of several proinflammatory and anti-inflammatory cytokines, including IL-6, CCL2, CCL11, CSF3, IL-8, IL-10, CX3CL1, and TNF-a, compared to those with lower clinical severity. Conclusions:Combining reductionist and systematic techniques may lead to a better understanding of the underlying complexities of the inflammatory reaction after aSAH. Neurology ® 2017;88:1535-1545 GLOSSARY aSAH 5 aneurysmal subarachnoid hemorrhage; CSF 5 colony-stimulating factor; DCI 5 delayed cerebral ischemia; EGF 5 epidermal growth factor; FGF-2 5 fibroblast growth factor-2; FLT3L 5 FMS-like tyrosine kinase 3 ligand; HH 5 Hunt-Hess; IFN-a2 5 interferon-a2; IFNG 5 type-II interferon family; IL 5 interleukin; MIP 5 macrophage inflammatory protein; Pcc 5 Pearson correlation coefficient; PDGF 5 platelet-derived growth factor; sCD40L 5 soluble CD40 ligand; SI 5 similarity index; TNF 5 tumor necrosis factor; VEGF 5 vascular endothelial growth factor.Aneurysmal subarachnoid hemorrhage (aSAH) affects z30,000 people annually and accounts for 10% to 15% of all strokes.1 Despite improvements in clinical management, morbidity after aSAH remains high. Studies have shown that early elevation of central and peripheral inflammatory cytokines is associated with delayed neurologic deteriorations.2 However, such studies typically use methods to examine differences in concentrations of individual cytokines across disease severity or clinical outcomes. They fail to account for the complexities an...

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confidence: 68%

Systematic model of peripheral inflammation after subarachnoid hemorrhage

Savarraj¹,

Parsha²,

Hergenroeder³

et al. 2017

Neurology

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“…16,40 Furthermore, it has been reported that levels of PDGF-BB concentration in the CSF in the acute phase of SAH patients were significantly higher in patients with rather than without symptomatic vasospasm. 41 Direct vasoconstrictive effects on arteries by exogenous PDGF are controversial in the literature. Recombinant PDGF has caused potent concentration-dependent contraction on rat aortic strips within 2 minutes after the application; however, it did not constrict rat intracerebral arterioles (perforating arteries) in vitro.…”

Section: Discussionmentioning

confidence: 99%

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

Zhang

Nagata

Kikuchi

et al. 2001

Stroke

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Background and Purpose-Plasma serine protease cascade, including the complement system and thrombin, is activated in the subarachnoid space during the acute phase after subarachnoid hemorrhage (SAH). To examine the effect of protease cascade-based inflammation and subsequent vascular repair in the development of cerebral vasospasm, we examined the effect of 2 synthetic serine protease inhibitors-FUT-175, an inhibitor of thrombin and the complement system, and argatroban, a selective inhibitor of thrombin-on the development of cerebral vasospasm in a rabbit SAH model. Methods-One hundred Japanese White male rabbits were used in the study. The SAH was simulated by a single injection of autologous arterial blood into the cisterna magna. To evaluate the development of cerebral vasospasm, the caliber of the basilar artery was measured on x-ray film before and at 2 days after SAH. Nine groups of rabbits (nϭ6 each) were treated with continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours, starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of platelet-derived growth factor-BB (PDGF-BB) in the basilar artery was examined with immunohistochemical techniques. In 20 normal rabbits, 5 g of recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the basilar arteries were examined on angiograms for 48 hours. Results-Significant differences were observed in the caliber of the basilar arteries between the vehicle group and the groups with the 3 larger doses of FUT-175 (vehicle, 52Ϯ5.0%; 5 mg, 79Ϯ5.7%; 10 mg, 80Ϯ2.5%; 20 mg, 80Ϯ3.7%) and between the vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52Ϯ6.4%; 2.5 mg, 81Ϯ9.0%; 5 mg, 85Ϯ4.1%) (PϽ0.05). In the histological examination, administration of effective doses of FUT-175 or argatroban suppressed the expression of PDGF-BB in the endothelial and medial smooth muscle cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on normal basilar arteries. Conclusions-Activation

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“…Clot removal, by either surgery (13) or intrathecal application of fibrinolytic agents such as urokinase or tissue plasminogen activator (16 -18), has (10,12,35), plasmin (36), fibrin degradation products (55,56) Platelet-derived substances: serotonin (57,58), thromboxane A2 (25, 59), platelet-derived growth factor (60) Prostaglandins: PGF2α (61, 62), PGE2 (63) Reactive oxygen species and related materials: lipid hydroperoxide (6) Lipid mediators: sphingosine 1-phosphate (64), arachidonic acid (65) Vasoactive substances: endothelin-1 (66,67), angiotensin II (57,58) Increased vascular responsiveness Endothelial damage and dysfunction (3) Increased contractile responsiveness of smooth muscle Increased receptor function: PAR1 (42,43), PDGFR (68) Alteration of signaling proteins: increased activity of Rho kinase (7, 8) Table 2. Current therapeutic strategies for the treatment of cerebral vasospasm…”

Section: Current Strategies For the Treatment Of Cerebral Vasospasmmentioning

confidence: 99%

Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage

et al. 2008

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Abstract. Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical role in the management of SAH patients. However, the mechanism of cerebral vasospasm still remains elusive, while effective therapeutic strategies also remain to be established. The role of thrombin and its receptor proteinase-activated receptor 1 (PAR 1 ) in cerebral vasospasm was investigated using a rabbit double hemorrhage SAH model. The expression of PAR 1 was up-regulated and the contractile response to thrombin was markedly enhanced in the basilar artery of SAH models. The intrathecal administration of a PAR 1 antagonist prevented the up-regulation of PAR 1 and the enhancement of the contractile responses to thrombin in SAH. These observations thus suggest that PAR 1 may play a pivotal role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin activates PAR 1 , thereby up-regulating the expression of PAR 1 , which culminates in the increased contractile response to thrombin in the basilar artery. PAR 1 antagonists are thus anticipated to be a novel therapeutic strategy for cerebral vasospasm. However, further studies are needed before establishing the clinical usefulness of PAR 1 antagonists.

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Platelet derived growth factor and subarachnoid haemorrage: A study on cisternal cerebrospinal fluid

Cited by 36 publications

References 30 publications

Systematic model of peripheral inflammation after subarachnoid hemorrhage

Systematic model of peripheral inflammation after subarachnoid hemorrhage

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage

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