Antivasospastic and antiinflammatory effects of caspase inhibitor in experimental subarachnoid hemorrhage

Iseda, Keiichi; Ono, Shigeki; Onoda, Keisuke; Satoh, Motoyoshi; Manabe, Hiroaki; Nishiguchi, Mitsuhisa; Takahashi, Kenji; Tokunaga, Koji; Sugiu, Kenji; Date, Isao

doi:10.3171/jns-07/07/0128

Cited by 35 publications

(17 citation statements)

References 32 publications

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“…Tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) have been shown to exert a pro-apoptotic effect on cultured cerebral microvascular endothelial cells [66]. In the experimental settings, caspase inhibitors have been shown to attenuate CVS after SAH and to reduce levels of inflammatory mediators including IL-1β [67]. Other studies further corroborated these results by showing that treatment with a broad caspase inhibitor decreased TNF-α expression in arterial wall and attenuated CVS [64].…”

Section: Hbo and Mechanisms Of Prolonged Vasoconstrictionmentioning

confidence: 99%

Hyperbaric Oxygen for Cerebral Vasospasm and Brain Injury Following Subarachnoid Hemorrhage

Ostrowski

Zhang

2011

Transl. Stroke Res.

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The impact of acute brain injury and delayed neurological deficits due to cerebral vasospasm (CVS) are major determinants of outcomes after subarachnoid hemorrhage (SAH). Although hyperbaric oxygen (HBO) had been used to treat patients with SAH, the supporting evidence and underlying mechanisms have not been systematically reviewed. In the present paper, the overview of studies of HBO for cerebral vasospasm is followed by a discussion of HBO molecular mechanisms involved in the protection against SAH-induced brain injury and even, as hypothesized, in attenuating vascular spasm alone. Faced with the paucity of information as to what degree HBO is capable of antagonizing vasospasm after SAH, the authors postulate that the major beneficial effects of HBO in SAH include a reduction of acute brain injury and combating brain damage caused by CVS. Consequently, authors reviewed the effects of HBO on SAH-induced hypoxic signaling and other mechanisms of neurovascular injury. Moreover, authors hypothesize that HBO administered after SAH may “precondition” the brain against the detrimental sequelae of vasospasm. In conclusion, the existing evidence speaks in favor of administering HBO in both acute and delayed phase after SAH; however, further studies are needed to understand the underlying mechanisms and to establish the optimal regimen of treatment.

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Section: Hbo and Mechanisms Of Prolonged Vasoconstrictionmentioning

confidence: 99%

Hyperbaric Oxygen for Cerebral Vasospasm and Brain Injury Following Subarachnoid Hemorrhage

Ostrowski

Zhang

2011

Transl. Stroke Res.

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“…The model using injection of autologous blood is more frequently used to study SAH since it has a low mortality rate. In this model, it has been shown that neuroinflammation starts within 3–6 hours after the injection of autologous blood and lasts for approximately 2 days [9]–[11]. Importantly, the long-term effects of SAH on neuroinflammation and damage are not known, as to the best of our knowledge in all studies, animals were terminated within a couple of days to maximum of a week, except for 3 studies in which the animals survived for 14 or 28 days post-SAH [12]–[14].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Functional Consequences and Ongoing Cerebral Inflammation after Subarachnoid Hemorrhage in the Rat

et al. 2014

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Subarachnoid hemorrhage (SAH) represents a considerable health problem with an incidence of 6–7 per 100.000 individuals per year in Western society. We investigated the long-term consequences of SAH on behavior, neuroinflammation and gray- and white-matter damage using an endovascular puncture model in Wistar rats. Rats were divided into a mild or severe SAH group based on their acute neurological score at 24 h post-SAH. The degree of hemorrhage determined in post-mortem brains at 48 h strongly correlated with the acute neurological score. Severe SAH induced increased TNF-α, IL-1β, IL-10, MCP-1, MIP2, CINC-1 mRNA expression and cortical neutrophil influx at 48 h post-insult. Neuroinflammation after SAH was very long-lasting and still present at day 21 as determined by Iba-1 staining (microglia/macrophages) and GFAP (astrocytes). Long-term neuroinflammation was strongly associated with the degree of severity of SAH. Cerebral damage to gray- and white-matter was visualized by immunohistochemistry for MAP2 and MBP at 21 days after SAH. Severe SAH induced significant gray- and white-matter damage. MAP2 loss at day 21 correlated significantly with the acute neurological score determined at 24 h post-SAH. Sensorimotor behavior, determined by the adhesive removal task and von Frey test, was affected after severe SAH at day 21. In conclusion, we are the first to show that SAH induces ongoing cortical inflammation. Moreover, SAH induces mainly cortical long-term brain damage, which is associated with long-term sensorimotor damage.

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“…Tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) have been shown to exert a pro-apoptotic effect on cultured cerebral microvascular endothelial cells [52]. In the experimental settings, caspase inhibitors have been shown to attenuate CVS after SAH and to reduce levels of inflammatory mediators including IL-1β [53]. Other studies further corroborated these results by showing that treatment with a broad caspase inhibitor decreased TNF-α expression in arterial wall and attenuated CVS [50].…”

Section: Pathophysiology Of Cerebral Vasospasmmentioning

confidence: 99%

Cerebral vasospasm: a review of current developments in drug therapy and research

Archavlis¹,

Nievas²

2013

J Pharm Technol Drug Res

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In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vasospasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Curent research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.

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Antivasospastic and antiinflammatory effects of caspase inhibitor in experimental subarachnoid hemorrhage

Abstract: These results indicate that caspase activation may be involved in the development of SAH-induced vasospasm through inflammatory reaction.

Cited by 35 publications

References 32 publications

Hyperbaric Oxygen for Cerebral Vasospasm and Brain Injury Following Subarachnoid Hemorrhage

Hyperbaric Oxygen for Cerebral Vasospasm and Brain Injury Following Subarachnoid Hemorrhage

Long-Term Functional Consequences and Ongoing Cerebral Inflammation after Subarachnoid Hemorrhage in the Rat

Cerebral vasospasm: a review of current developments in drug therapy and research

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