Systemic Administration of Simvastatin after the Onset of Experimental Subarachnoid Hemorrhage Attenuates Cerebral Vasospasm

McGirt, Matthew J.; Pradilla, Gustavo; Legnani, Federico; Thai, Quoc Anh; Recinos, Pablo F.; Tamargo, Rafael J.; Clatterbuck, Richard E.

doi:10.1227/01.neu.0000210262.67628.7e

Cited by 78 publications

(64 citation statements)

References 37 publications

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“…17,18 Furthermore, sepsis and systemic inflammatory response syndromes are known to be associated with the occurrence of vasospasm, and the increased metabolic demand with sepsis potentially aggravates processes of cerebral ischemia. 16 Statin therapy may counteract these events by inhibiting the C-reactive protein and lipopolysaccharideinduced inflammatory cascades.…”

Section: Effects On Rescue Therapymentioning

confidence: 99%

Effects of Acute Pravastatin Treatment on Intensity of Rescue Therapy, Length of Inpatient Stay, and 6-Month Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage

Tseng

Hutchinson

Czosnyka

et al. 2007

Stroke

133

102

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Background and Purpose-We have previously demonstrated that acute pravastatin therapy after aneurysmal subarachnoid hemorrhage ameliorates vasospasm-related delayed ischemic deficits. This study assesses the effects of pravastatin on the frequency and intensity for rescue therapy, length of inpatient stay, and long-term outcome at 6 months. Methods-Eighty aneurysmal subarachnoid hemorrhage patients (age 18 to 84 years, onset 1.8Ϯ1.3 days) were randomized to receive daily oral pravastatin (40 mg) or placebo for up to 14 days. Clinical events were recorded during the trial. Six-month outcome was assessed using the Short Form 36 and the modified Rankin Scale. Results-Although no significant difference in the outcome at discharge was found between the trial groups, multivariate analysis showed pravastatin therapy reduced unfavorable outcome by 73% (Pϭ0.041). The benefit persisted at 6 months (Pϭ0.063) and was notable in the physical (PϽ0.001) and psychosocial (PϽ0.001) aspects measured using Short Form 36. Furthermore, the acute pravastatin therapy reduced the requirement for triple-H therapy (hypertensive, hypervolemic, hemodilution; Pϭ0.045) and mortality related to vasospasm (Pϭ0.02) and sepsis (Pϭ0.001); no significant difference was found in the length of inpatient stay between the trial groups. Conclusions-This trial demonstrates that acute statin treatment reduces traditional rescue therapy for vasospasm after aneurysmal subarachnoid hemorrhage. Improvement in early outcome has proved robust at 6 months, particularly in relation to physical and psychosocial (Short Form 36) outcome.

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Section: Effects On Rescue Therapymentioning

confidence: 99%

Effects of Acute Pravastatin Treatment on Intensity of Rescue Therapy, Length of Inpatient Stay, and 6-Month Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage

Tseng

Hutchinson

Czosnyka

et al. 2007

Stroke

133

102

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show abstract

“…Statins affect the endothelium through increased nitric oxide bioavailability 3 and have been shown to ameliorate SAH-induced vasospasm. 4 Although statins decrease cerebrovascular event rates during use, withdrawal of statins causes a rebound effect leading to increases in vascular event rates beyond that of the absence of prevention alone. 5 This observed rebound effect has been attributed to the inhibition of endothelium NOS (eNOS)-mediated pathways by statins.…”

mentioning

confidence: 99%

Withdrawal of Statins and Risk of Subarachnoid Hemorrhage

Risselada

Straatman

Kooten

et al. 2009

Stroke

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“…Previous evidence revealed that simvastatin exhibits beneficial effects for patients with intracerebral hemorrhage (20). In addition, simvastatin has been demonstrated to attenuate cerebral vasospasm and improve the treatment outcomes by upregulation of various signaling pathways in a rat model of subarachnoid hemorrhage (21).…”

Section: Discussionmentioning

confidence: 99%

Simvastatin improves intracerebral hemorrhage through NF‑κB‑mediated apoptosis via the MyD88/TRIF signaling pathway

Fan

et al. 2017

Exp Ther Med

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Abstract. The aim was to investigate the neuroprotective effects and potential mechanism mediated by simvastatin in a mouse model of intracerebral hemorrhage. CD-1 mice were subjected to infusion of collagenase type IV into the left striatum in order to induce intracerebral hemorrhage. Western blot analysis, the TUNEL assay and the modified neurological severity score were used in the present study to analyze the efficacy of simvastatin for intracerebral hemorrhage. The results demonstrated that simvastatin treatment improved the cerebral water content and blood-brain barrier disruption in the intracerebral hemorrhage animals. Intracerebral hemorrhage-induced neuronal cell death was downregulated by simvastatin treatment compared with the vehicle-treated model group. In addition, the expression levels of aquaporin-4, matrix metallopeptidase 9 and caspase-3 were downregulated and B-cell lymphoma-2 was upregulated by simvastatin treatment compared with the vehicle-treated model. Simvastatin treatment also significantly reduced the Evans blue leakage into the injured hemispheres and improved motor function. Mechanism analysis further indicated that simvastatin treatment downregulated nuclear factor (NF)-κB expression, and upregulated the myeloid differentiation primary response 88 (MyD88) and TIR domain-containing adaptor protein inducing interferon-β (TRIF) expression levels in neuronal cells in experimental mice. Furthermore, the results revealed that NF-κB overexpression abolished the simvastatin-downregulated MyD88 and TRIF expression levels, as well as the apoptosis of neuronal cells. In conclusion, these results indicated that simvastatin was able to attenuate brain edema and reduce cellular apoptosis by suppressing the NF-κB-mediated MyD88/TRIF signaling pathway subsequent to the induction of intracerebral hemorrhage in mice.

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Systemic Administration of Simvastatin after the Onset of Experimental Subarachnoid Hemorrhage Attenuates Cerebral Vasospasm

Cited by 78 publications

References 37 publications

Effects of Acute Pravastatin Treatment on Intensity of Rescue Therapy, Length of Inpatient Stay, and 6-Month Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage

Effects of Acute Pravastatin Treatment on Intensity of Rescue Therapy, Length of Inpatient Stay, and 6-Month Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage

Withdrawal of Statins and Risk of Subarachnoid Hemorrhage

Simvastatin improves intracerebral hemorrhage through NF‑κB‑mediated apoptosis via the MyD88/TRIF signaling pathway

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