Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function.

A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein-coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age-related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes.

Safety of stereotactic laser ablations performed as treatment for glioblastomas in a conventional magnetic resonance imaging suite.

OBJECTIVE Stereotactic laser ablation (SLA) is typically performed in the setting of intraoperative MRI or in a staged manner in which probe insertion is performed in the operating room and thermal ablation takes place in an MRI suite. METHODS The authors describe their experience, in which SLA for glioblastoma (GBM) treatment was performed entirely within a conventional MRI suite using the SmartFrame stereotactic device. RESULTS All 10 patients with GBM (2 with isocitrate dehydrogenase 1 mutation [mIDH1] and 8 with wild-type IDH1 [wtIDH1]) were followed for > 6 months. One of these patients underwent 2 independent SLAs approximately 12 months apart. Biopsies were performed prior to SLA for all patients. There were no perioperative morbidities, wound infections, or unplanned 30-day readmissions. The average time for a 3-trajectory SLA (n = 3) was 436 ± 102 minutes; for a 2-trajectory SLA (n = 4) was 321 ± 85 minutes; and for a single-trajectory SLA (n = 4) was 254 ± 28 minutes. No tumor recurrence occurred within the blue isotherm line ablation zone, although 2 patients experienced recurrence immediately adjacent to the blue isotherm ablation line. Overall survival for the patient cohort averaged 356 days, with the 2 patients who had mIDH1 GBMs exhibiting the longest survival (811 and 654 days). CONCLUSIONS Multitrajectory SLA for treatment of GBM can be safely performed using the SmartFrame stereotactic device in a conventional MRI suite.

Stereotactic laser ablation as treatment for brain metastases that recur after stereotactic radiosurgery: a multiinstitutional experience.

OBJECTIVE Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited. METHODS The authors provide the collective experience of 4 institutions where treatment of BMs that recurred after SRS was performed with stereotactic laser ablation (SLA). RESULTS Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (2 patients each underwent 2 SLAs for separate lesions, and a third underwent 2 serial SLAs for discrete BMs). Histological findings in the BMs treated included the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2); ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1). With a median follow-up duration of 141 days (range 64-794 days), 9 of the SLA-treated BMs progressed despite treatment (35%). All cases of progression occurred in BMs in which < 80% ablation was achieved, whereas no disease progression was observed in BMs in which ≥ 80% ablation was achieved. Five BMs were treated with SLA, followed 1 month later by adjuvant SRS (5 Gy daily × 5 days). No disease progression was observed in these patients despite ablation efficiency of < 80%, suggesting that adjuvant hypofractionated SRS enhances the efficacy of SLA. Of the 23 SLA-treated patients, 3 suffered transient hemiparesis (13%), 1 developed hydrocephalus requiring temporary ventricular drainage (4%), and 1 patient who underwent SLA of a 28.9-cm3 lesion suffered a neurological deficit requiring an emergency hemicraniectomy (4%). Although there is significant heterogeneity in corticosteroid treatment post-SLA, most patients underwent a 2-week taper. CONCLUSIONS Stereotactic laser ablation is an effective treatment option for BMs in which SRS fails. Ablation of ≥ 80% of BMs is associated with decreased risk of disease progression. The efficacy of SLA in this setting may be augmented by adjuvant hypofractionated SRS.

Association of amisulpride and recovery room length of stay among patients with postoperative nausea and vomiting following outpatient surgery.

STUDY OBJECTIVE: Postoperative nausea and vomiting (PONV) is a common sequela of surgery in patients undergoing general anesthesia. Amisulpride has shown promise in its ability to treat PONV. The objective of this study was to determine if amisulpride is associated with significant changes in PACU efficiency within a fast-paced ambulatory surgery center. METHODS: This was a retrospective cohort study of 816 patients at a single ambulatory surgery center who experienced PONV between 2018 and 2023. The two cohorts analyzed were patients who did or did not have amisulpride among their anti-emetic regimens in the PACU during two distinct time periods (before and after amisulpride was introduced). The primary outcome of the study was PACU length of stay. Both unmatched analysis and a linear multivariable mixed-effects model fit by restricted maximum likelihood (random effect being surgical procedure) were used to analyze the association between amisulpride and PACU length of stay. We performed segmented regression to account for cohorts occurring during two time periods. RESULTS: Unmatched univariate analysis revealed no significant difference in PACU length of stay (minutes) between the amisulpride and no amisulpride cohorts (115 min vs 119 min, respectively; P = 0.07). However, when addressing confounders by means of the mixed-effects multivariable segmented regression, the amisulpride cohort was associated with a statistically significant reduction in PACU length of stay by 26.1 min (P < 0.001). CONCLUSIONS: This study demonstrated that amisulpride was associated with a significant decrease in PACU length of stay among patients with PONV in a single outpatient surgery center. The downstream cost-savings and operational efficiency gained from this drug's implementation may serve as a useful lens through which this drug's widespread implementation may further be rationalized.

Isoflurane neurotoxicity is mediated by p75NTR-RhoA activation and actin depolymerization.

BACKGROUND: The mechanisms by which isoflurane injured the developing brain are not clear. Recent work has demonstrated that it is mediated in part by activation of p75 neurotrophin receptor. This receptor activates RhoA, a small guanosine triphosphatase that can depolymerize actin. It is therefore conceivable that inhibition of RhoA or prevention of cytoskeletal depolymerization might attenuate isoflurane neurotoxicity. This study was conducted to test these hypotheses using primary cultured neurons and hippocampal slice cultures from neonatal mouse pups. METHODS: Primary neuron cultures (days in vitro, 4-7) and hippocampal slice cultures from postnatal day 4-7 mice were exposed to 1.4% isoflurane (4 h). Neurons were pretreated with TAT-Pep5, an intracellular inhibitor of p75 neurotrophin receptor, the cytoskeletal stabilizer jasplakinolide, or their corresponding vehicles. Hippocampal slice cultures were pretreated with TAT-Pep5 before isoflurane exposure. RhoA activation was evaluated by immunoblot. Cytoskeletal depolymerization and apoptosis were evaluated with immunofluorescence microscopy using drebrin and cleaved caspase-3 staining, respectively. RESULTS: RhoA activation was increased after 30 and 120 min of isoflurane exposure in neurons; TAT-Pep5 (10 µm) decreased isoflurane-mediated RhoA activation at both time intervals. Isoflurane decreased drebrin immunofluorescence and enhanced cleaved caspase-3 in neurons, effects that were attenuated by pretreatment with either jasplakinolide (1 µm) or TAT-Pep5. TAT-Pep5 attenuated the isoflurane-mediated decrease in phalloidin immunofluorescence. TAT-Pep5 significantly attenuated isoflurane-mediated loss of drebrin immunofluorescence in hippocampal slices. CONCLUSIONS: Isoflurane results in RhoA activation, cytoskeletal depolymerization, and apoptosis. Inhibition of RhoA activation or prevention of downstream actin depolymerization significantly attenuated isoflurane-mediated neurotoxicity in developing neurons.

Acute Ischemic Stroke.

Anesthesiologists provide care to acute and subacute ischemic stroke (IS) patients and stroke survivors in interventional radiology, intensive care, and operating rooms. These encounters will become more frequent following studies that have extended the treatment window from last known well time for fibrinolytic and endovascular thrombectomy (EVT). The number of stroke centers certified to quickly and effectively initiate treatment of IS patients and the number of patients connected to them by telehealth continue to grow. This article reviews IS pathophysiology, assessment, treatment, pathology, and complications; anesthetic management during EVT; perioperative stroke management; and how anesthesia has an impact on patients with prior stroke.

Real-time Magnetic Resonance Imaging-Guided Biopsy Using SmartFrame® Stereotaxis in the Setting of a Conventional Diagnostic Magnetic Resonance Imaging Suite.

BACKGROUND: Real-time magnetic resonance imaging (MRI) visualization during stereotactic needle biopsies affords several valuable benefits to the neurosurgeon, including the opportunity to visually confirm the biopsy site at the time of surgery. Until now, reported experiences with this technique have been limited to the setting of intraoperative MRI or dedicated procedural MRI suites with modified ventilation systems. OBJECTIVE: To describe our experience with 11 consecutive patients who underwent real-time MRI-guided biopsy performed using SmartFrame® stereotaxis (MRI Interventions, Irvine, California) in the setting of a conventional diagnostic MRI suite. METHODS: This is a case series of patients that underwent real-time MRI-guided biopsy at a single institution. RESULTS: Four of the 11 lesions were previously biopsied by experienced neurosurgeons, yielding tissues that were nondiagnostic. Six of these lesions were sub-cubic centimeter in volume. One lesion was associated with aberrant venous anatomy. Two patients underwent laser thermal ablation in the same setting. There were no perioperative complications or unplanned 30-day readmission. All patients were discharged on postoperative day 1 to home. The operative time for the biopsy averaged 165 ± 24 min. Illustrative examples are reviewed. CONCLUSION: Real-time MRI-guided needle biopsy can be safely performed in the setting of a conventional diagnostic MRI suite. This technique provides neurosurgeons with the opportunity to visualize and confirm the biopsy site and allows for real-time adjustments in surgical maneuvers.

The Effect of Clevidipine on Cerebral Blood Flow Velocity and Carbon Dioxide Reactivity in Human Volunteers.

BACKGROUND: Clevidipine is a short acting, esterase metabolized, calcium channel antagonist administered as a continuous infusion for control of hypertension. Its profile allows for rapid titration and may be uniquely suited to achieving tight hemodynamic targets in neurosurgical and neurocritical care patients. The present study was designed to investigate the effect of clevidipine infusion on cerebral blood flow and cerebral CO2 responsiveness as measured by cerebral blood flow velocity (CBFV) using transcranial Doppler. MATERIALS AND METHODS: CBFV was continuously recorded in 5 healthy subjects during the following conditions: baseline 1 (BL1); baseline with hyperventilation (HV1); baseline 2 (BL2); clevidipine infusion to achieve 15% mean arterial pressure (MAP) reduction (C15); clevidipine infusion to achieve 30% MAP reduction (C30); clevidipine infusion to 30% MAP reduction with hyperventilation (HV2). RESULTS: The mean CBFV during intermediate (C15) or maximum (C30) dose clevidipine infusion was unchanged compared with baseline (BL2) (F2,8=0.66; P=0.54). Cerebral CO2 reactivity, expressed as %[INCREMENT]CBFV/[INCREMENT]mm Hg CO2, was not significantly different in the presence of maximal-dose clevidipine (HV2) as compared with baseline (HV1) (1.6±0.4 vs. 1.6±0.3%[INCREMENT]CBFV/[INCREMENT]mm Hg CO2, P=0.73). CONCLUSIONS: Clevidipine infusion did not significantly increase CBFV nor was cerebral CO2 reactivity reduced during maximal-dose clevidipine infusion. Further systematic investigation of clevidipine in patients with central nervous system pathology seems justified.