Acta neurochirurgica. Supplement
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Acta Neurochir. Suppl. · Jan 2015
ReviewIntrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.
The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. ⋯ Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release nimOdipine MIcro particles after Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal EG-1962 administration. The NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing EG-1962 and nimodipine in patients with aneurysmal SAH.
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Acta Neurochir. Suppl. · Jan 2015
Multicenter StudyCharacteristics of patients without neuropsychological deficits following aneurysmal subarachnoid haemorrhage.
Previous studies have shown that the incidence of neuropsychological deficits (NPD) after aneurysmal subarachnoid haemorrhage (aSAH) is high despite excellent outcome evaluated by traditional neurological grading scales. The aim of this study was to elucidate the clinical characteristics in patients presenting with aSAH who had a good clinical outcome without NPD. ⋯ Patients without NPD after aSAH are likely to present with mild admission scores, develop neither chronic hydrocephalus nor DCI. In this series the aneurysm occlusion modality did not influence the cognitive outcome.
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Acta Neurochir. Suppl. · Jan 2015
Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
Tenascin-C (TNC), a matricellular protein, exerts diverse functions, including tissue remodeling and apoptosis, and is induced in cerebrospinal fluid (CSF) after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationships among CSF TNC levels, initial brain injury, delayed cerebral ischemia (DCI), and vasospasm after SAH. ⋯ SAH (initial brain injury) that is more severe induces more TNC, which may cause the subsequent development of both vasospasm and vasospasm-unrelated secondary brain injury, leading to DCI.
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Acta Neurochir. Suppl. · Jan 2015
Effects of tenascin-C on early brain injury after subarachnoid hemorrhage in rats.
We previously reported that tenascin-C (TNC), a matricellular protein, was involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the role of TNC in early brain injury (EBI) is unknown. This study assessed whether inhibition of TNC upregulation in brain by imatinib mesylate (imatinib), an inhibitor of the tyrosine kinases of platelet-derived growth factor receptors, prevents EBI after experimental SAH. ⋯ TNC may be involved in the pathogenesis of EBI after SAH.
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Acta Neurochir. Suppl. · Jan 2015
ReviewNeurovascular events after subarachnoid hemorrhage: focusing on subcellular organelles.
Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Early brain injury (EBI) and cerebral vasospasm (CVS) are the two most important pathophysiological mechanisms for brain injury and poor outcomes for patients with SAH. CVS has traditionally been considered the sole cause of delayed ischemic neurological deficits after SAH. ⋯ The dysfunction of subcellular organelles, such as endoplasmic reticulum stress, mitochondrial failure, and autophagy-lysosomal system activation, has developed during EBI and delayed brain injury after SAH. To our knowledge, there is a lack of review articles addressing the direction of organelle dysfunction after SAH. In this review, we discuss the roles of organelle dysfunction in the pathogenesis of SAH and present the opportunity to develop novel therapeutic strategies of SAH via modulating the functions of organelles.