Therapeutically Targeting Platelet-Derived Growth Factor-Mediated Signaling Underlying the Pathogenesis of Subarachnoid Hemorrhage-Related Vasospasm

Ghali, Michael George Zaki; Srinivasan, Visish M.; Johnson, J.K.; Kan, Peter; Britz, Gavin W.

doi:10.1016/j.jstrokecerebrovasdis.2018.02.017

Cited by 12 publications

(15 citation statements)

References 103 publications

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“…These inflammatory cells secrete cytokines that trigger a fibroproliferative reaction by acting as mitogens and chemoattractants for fibroblasts. Reportedly, inflammatory cytokines and growth factors such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF), and transforming growth factor (TGF)-β are upregulated in the acute stage of aSAH [ 31 , 32 , 33 ]. Thrombin is also released by the blood-clotting cascade in the CSF of patients with aSAH [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

Kuo

Huang

2021

IJMS

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Hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH) and reportedly contributes to poor neurological outcomes. In this review, we summarize the molecular and cellular mechanisms involved in the pathogenesis of hydrocephalus following aSAH and summarize its treatment strategies. Various mechanisms have been implicated for the development of chronic hydrocephalus following aSAH, including alterations in cerebral spinal fluid (CSF) dynamics, obstruction of the arachnoid granulations by blood products, and adhesions within the ventricular system. Regarding molecular mechanisms that cause chronic hydrocephalus following aSAH, we carried out an extensive review of animal studies and clinical trials about the transforming growth factor-β/SMAD signaling pathway, upregulation of tenascin-C, inflammation-dependent hypersecretion of CSF, systemic inflammatory response syndrome, and immune dysregulation. To identify the ideal treatment strategy, we discuss the predictive factors of shunt-dependent hydrocephalus between surgical clipping and endovascular coiling groups. The efficacy and safety of other surgical interventions including the endoscopic removal of an intraventricular hemorrhage, placement of an external ventricular drain, the use of intraventricular or cisternal fibrinolysis, and an endoscopic third ventriculostomy on shunt dependency following aSAH were also assessed. However, the optimal treatment is still controversial, and it necessitates further investigations. A better understanding of the pathogenesis of acute and chronic hydrocephalus following aSAH would facilitate the development of treatments and improve the outcome.

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Section: Introductionmentioning

confidence: 99%

The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

Kuo

Huang

2021

IJMS

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“…PDGF-β has also been reported to positively correlate with incidence and severity of vasospasm after aSAH, 49,50 and in animals models. 55,58 Experimentally, vasospasm increases as plasma levels of PDGF-β rise 55 and use of a PDGF antagonist can prevent vasospasm.…”

Section: Platelets Induce Vessel Constrictionmentioning

confidence: 93%

Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage

Dienel

Blackburn

et al. 2021

J Cereb Blood Flow Metab

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Aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral ischemia and delayed deficits (DCI) within 2 weeks of aneurysm rupture at a rate of approximately 30%. DCI is a major contributor to morbidity and mortality after SAH. The cause of DCI is multi-factorial with contributions from microthrombi, blood vessel constriction, inflammation, and cortical spreading depolarizations. Platelets play central roles in hemostasis, inflammation, and vascular function. Within this review, we examine the potential roles of platelets in microthrombi formation, large artery vasospasm, microvessel constriction, inflammation, and cortical spreading depolarization. Evidence from experimental and clinical studies is provided to support the role(s) of platelets in each pathophysiology which contributes to DCI. The review concludes with a suggestion for future therapeutic targets to prevent DCI after aSAH.

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“…The number of White Blood Cells [WBC], Platelet [PLT], Absolute Neutrophil [ANC] and Absolute Lymphocyte Counts [ALC] were obtained by automated test system systems Hitachi 7600 and BM2000 on admission. The severity of aSAH was assessed by Glasgow Coma Scale (GCS) on admission and the scores were divided into three levels: severe (13)(14)(15), moderate (9)(10)(11)(12), and mild (3)(4)(5)(6)(7)(8). The SII (10 9 /L) was calculated as following formula: PLT (10 9 /L) x ANC (10 9 /L)/ALC (10 9 /L) [12].…”

Section: Methodsmentioning

confidence: 99%

“…Thirty to 50% of SAH survivors develop delayed neurological dysfunction(DND)and has unfavorable outcomes leading to decreased quality of life and increased societal monetary burden [6,14]. Because of complex pathophysiology in early and delayed brain damage, in ammation after bleeding is an important factor affecting the prognosis of aneurysms [2,22,25].At present, indicators such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutrition index (PNI), MMP-9, TNF-a, IL-6 have shown associations with clinical complications and outcomes in aSAH [4,5,7,10]. However, prediction effects of these indicators on aSAH prognosis were not satisfactory and contradictory ndings exited in current studies.…”

Section: Introductionmentioning

confidence: 99%