Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established. Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6′dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining. TNF-α knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-α protein and mRNA expression was not significantly different in TNF-α knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture. These data suggest a critical role of TNF-α in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-α could be beneficial in preventing aneurysmal progression and rupture.

Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored. In vitro neuronal culture with oxygen-glucose deprivation and rats with middle cerebral artery occlusion were subjected to DMF/MMF treatment. Live/dead cell counting and LDH assay, as well as behavioral deficits, plasma cytokine assay, western blots, real-time PCR (Q-PCR) and immunofluorescence staining, were used to evaluate the mechanisms and neurological outcomes. We found that MMF significantly rescued cortical neurons from oxygen-glucose deprivation (OGD) in culture and suppressed pro-inflammatory cytokines produced by primary mixed neuron/glia cultures subjected to OGD. In rats, DMF treatment significantly decreased infarction volume by nearly 40 % and significantly improved neurobehavioral deficits after middle cerebral artery occlusion (MCAO). In the acute early phase (72 h after MCAO), DMF induced the expression of transcription factor Nrf2 and its downstream mediator HO-1, important for the protection of infarcted cells against oxidative stress. In addition to its antioxidant role, DMF also acted as a potent immunomodulator, reducing the infiltration of neutrophils and T cells and the number of activated microglia/macrophages in the infarct region by more than 50 % by 7–14 days after MCAO. Concomitantly, the levels of potentially harmful pro-inflammatory cytokines were greatly reduced in the plasma and brain and in OGD neuron/glia cultures. We conclude that DMF is neuroprotective in experimental stroke because of its potent immunomodulatory and antioxidant effects and thus may be useful as a novel therapeutic agent to treat stroke in patients.

Traumatic intracranial pseudoaneurysms remain one of the most difficult vascular lesions to treat. In the case of traumatic pseudoaneurysms that may not be treated with parent vessel sacrifice, some flow diversion strategy such as stent-assistance or use of a flow diversion device is usually necessary. In this study we describe endovascular parent vessel wall-remodeling/endoluminal reconstruction and traumatic pseudoaneurysm thrombosis through the use of the Pipeline stent and review recent reports concerning indications, safety, and efficacy for alternative pathology. Although currently not routinely employed in the treatment of traumatic pseudoaneurysms, the Pipeline stent may represent a safe and effective treatment alternative achieving complete endoluminal reconstruction of the damaged vessel wall.

BACKGROUND AND PURPOSE: The use of the Pipeline Embolization Device in the management of recurrent previously stented cerebral aneurysms is controversial. The aim of this study was to evaluate the efficacy and safety of the Pipeline Embolization Device in the treatment of recurrent, previously stented aneurysms. MATERIALS AND METHODS: Twenty-one patients with previously stented recurrent aneurysms who later underwent Pipeline Embolization Device placement (group 1) were retrospectively identified and compared with 63 patients who had treatment with the Pipeline Embolization Device with no prior stent placement (group 2). Occlusion at the latest follow-up angiogram, recurrence and retreatment rates, clinical outcome, complications, and morbidity and mortality observed after treatment with the Pipeline Embolization Device were analyzed. RESULTS: Patient characteristics were similar between the 2 groups. The mean time from stent placement to recurrence was 25 months. Pipeline Embolization Device treatment resulted in complete aneurysm occlusion in 55.6% of patients in group 1 versus 80.4% of patients in group 2 (P = .036). The retreatment rate in group 1 was 11.1% versus 7.1% in group 2 (P = .62). The rate of good clinical outcome at the latest follow-up in group 1 was 81% versus 93.2% in group 2 (P = .1). Complications were observed in 14.3% of patients in group 1 and 9.5% of patients in group 2 (P = .684). CONCLUSIONS: The use of the Pipeline Embolization Device in the management of previously stented aneurysms is less effective than the use of this device in nonstented aneurysms. Prior stent placement can worsen the safety and efficacy profile of this device.

Endovascular therapy is now the treatment of choice for intracranial aneurysms (IAs) for its efficacy and safety profile. The use of flow diversion (FD) has recently expanded to cover many types of IAs in various locations. Some institutions even attempt FD as first line treatment for unruptured IAs. The most widely used devices are the pipeline embolization device (PED), the SILK flow diverter (SFD), the flow redirection endoluminal device (FRED), and Surpass. Many questions were raised regarding the long-term complications, the optimal regimen of dual antiplatelet therapy, and the durability of treatment effect. We reviewed the literature to address these questions as well as other concerns on FD when treating IAs.