Role of Platelet-Derived Growth Factor in Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats

Shiba, Masato; Suzuki, Hitomi; Fujimoto, Masashi; Shimojo, Naoshi; Imanaka‐Yoshida, Kyoko; Yoshida, Toshimichi; Kanamaru, Kenji; Matsushima, Satoshi; Taki, Waro

doi:10.1007/978-3-7091-1192-5_40

Cited by 14 publications

(9 citation statements)

References 15 publications

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“…Inhibition of the tyrosine kinases of PDGFRs by imatinib reduces post‐SAH vasospasm, being associated with suppressing the expression level of PDGFR‐β, TNC, and p38 activation (Shiba et al, ). Direct injections of recombinant TNC into subarachnoid induces prolonged constriction of rat basilar arteries (Fujimoto et al, ; Shiba et al, ), being accompanied by upregulation of PDGFR‐β and endogenous TNC, and enhanced PDGFR phosphorylation (Shiba et al, ).…”

Section: Tenascin‐cmentioning

confidence: 99%

Tenascin‐C in Development and Disease of Blood Vessels

Imanaka‐Yoshida

Yoshida

Miyagawa‐Tomita

2014

The Anatomical Record

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Tenascin-C (TNC) is an extracellular glycoprotein categorized as a matricellular protein. It is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion, and has a wide range of effects on cell response in tissue morphogenesis and remodeling including the cardiovascular system. In the heart, TNC is sparsely detected in normal adults but transiently expressed at restricted sites during embryonic development and in response to injury, playing an important role in myocardial remodeling. Although TNC in the vascular system appears more complex than in the heart, the expression of TNC in normal adult blood vessels is generally low. During embryonic development, vascular smooth muscle cells highly express TNC on maturation of the vascular wall, which is controlled in a way that depends on the embryonic site of cell origin. Strong expression of TNC is also linked with several pathological conditions such as cerebral vasospasm, intimal hyperplasia, pulmonary artery hypertension, and aortic aneurysm/ dissection. TNC synthesized by smooth muscle cells in response to developmental and environmental cues regulates cell responses such as proliferation, migration, differentiation, and survival in an autocrine/ paracrine fashion and in a context-dependent manner. Thus, TNC can be a key molecule in controlling cellular activity in adaptation during normal vascular development as well as tissue remodeling in pathological conditions. Anat Rec, 297:1747Rec, 297: -1757Rec, 297: , 2014. V C 2014 Wiley Periodicals, Inc.Key words: muscle; tenascin-C; blood vessel Abbreviations used: ECM 5 extracellular matrix; TNC 5 tenascin-C; VSMC 5 vascular smooth muscle cell; aSMA 5 a-smooth muscle actin; SAH 5 subarachnoid hemorrhage.

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Section: Tenascin‐cmentioning

confidence: 99%

Tenascin‐C in Development and Disease of Blood Vessels

Imanaka‐Yoshida

Yoshida

Miyagawa‐Tomita

2014

The Anatomical Record

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“…Many reports have provided experimental evidence for efficacy of TKIs in several neurological and non-neurological disorders, including among others ischemic and hemorrhagic brain stroke [ 1 , 2 ], Alzheimer’s disease [ 3 ], multiple sclerosis [ 4 ], rheumatoid arthritis [ 5 ], asthma [ 6 ], mastocytosis [ 7 ] and other. Thus, TKIs may represent an innovative avenue for treatment of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitor as a new Therapy for Ischemic Stroke and other Neurologic Diseases: is there any Hope for a Better Outcome?

Gągało¹,

Rusiecka²,

Kocić

2015

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The relevance of tyrosine kinase inhibitors (TKIs) in the treatment of malignancies has been already defined. Aberrant activation of tyrosine kinase signaling pathways has been causally linked not only to cancers but also to other non-oncological diseases. This review concentrates on the novel plausible usage of this group of drugs in neurological disorders, such as ischemic brain stroke, subarachnoid hemorrhage, Alzheimer’s disease, multiple sclerosis. The drugs considered here are representatives of both receptor and non-receptor TKIs. Among them imatinib and masitinib have the broadest spectrum of therapeutic usage. Both drugs are effective in ischemic brain stroke and multiple sclerosis, but only imatinib produces a therapeutic effect in subarachnoid hemorrhage. Masitinib and dasatinib reduce the symptoms of Alzheimer’s disease. In the case of multiple sclerosis several TKIs are useful, including apart from imatinib and masitinib, also sunitinib, sorafenib, lestaurtinib. Furthermore, the possible molecular targets for the drugs are described in connection with the underlying pathophysiological mechanisms in the diseases in question. The most frequent target for the TKIs is PDGFR which plays a pivotal role particularly in ischemic brain stroke and subarachnoid hemorrhage. The collected data indicates that TKIs are very promising candidates for new therapeutic interventions in neurological diseases.

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“…To confirm this, we examined several of the key pathophysiological brain injury processes known to occur after SAH, and found that astrocyte and microglial activation, BBB disruption, and microvessel thrombosis can be easily detected in ROX SE perfused tissue. In contrast, immunohistochemical studies in brains that have been casted with India ink-gelatin, though possible 59 , 60 , are quite challenging and often yield poor results due to the pervasive black background. These advantages of superior inter-observer reliability along with the ability to utilize ROX SE stained tissue for histological studies would be expected to lower the number of animals needed per experiment and therefore offer higher cost-effectiveness.…”

Section: Discussionmentioning

confidence: 99%

A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage

Aum

Vellimana

Singh

et al. 2017

Sci Rep

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Various techniques have been developed to study changes in the cerebral vasculature in numerous neuropathological processes including subarachnoid hemorrhage (SAH). One of the most widely employed techniques uses India ink-gelatin casting, which presents numerous challenges due to its high viscosity, rapid solidification, and its impact on immunohistochemical analysis. To overcome these limitations, we developed a novel technique for assessing cerebral vasospasm using cerebrovascular perfusion with ROX, SE (5-Carboxy-X-Rhodamine, Succinimidyl Ester), a fluorescent labeling dye. We found that ROX SE perfusion achieves excellent delineation of the cerebral vasculature, was qualitatively and quantitatively superior to India ink-gelatin casting for the assessment of cerebral vasospasm, permits outstanding immunohistochemical examination of non-vasospasm components of secondary brain injury, and is a more efficient and cost-effective experimental technique. ROX SE perfusion is therefore a novel and highly useful technique for studying cerebrovascular pathology following experimental SAH.

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Role of Platelet-Derived Growth Factor in Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats

Abstract: PDGF may play an important role in the pathogenesis of vasospasm after SAH.

Cited by 14 publications

References 15 publications

Tenascin‐C in Development and Disease of Blood Vessels

Tenascin‐C in Development and Disease of Blood Vessels

Tyrosine Kinase Inhibitor as a new Therapy for Ischemic Stroke and other Neurologic Diseases: is there any Hope for a Better Outcome?

A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage

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