Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models.

PURPOSE: Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux. METHODS: Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell(®) models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure. RESULTS: AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs. CONCLUSIONS: Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.

Vagal nerve stimulation: overview and implications for anesthesiologists.

Vagal nerve stimulation is an important adjunctive therapy for medically refractory epilepsy and major depression. Additionally, it may prove effective in treating obesity, Alzheimer's disease, and some neuropsychiatic disorders. As the number of approved indications increases, more patients are becoming eligible for surgical placement of a commercial vagal nerve stimulator (VNS). Initial VNS placement typically requires general anesthesia, and patients with previously implanted devices may present for other surgical procedures requiring anesthetic management. In this review, we will focus on the indications for vagal nerve stimulation (both approved and experimental), proposed therapeutic mechanisms for vagal nerve stimulation, and potential perioperative complications during initial VNS placement. Anesthetic considerations during initial device placement, as well as anesthetic management issues for patients with a preexisting VNS, are reviewed.