Wireless, Battery-Free Implants for Electrochemical Catecholamine Sensing and Optogenetic Stimulation.

Neurotransmitters and neuromodulators mediate communication between neurons and other cell types; knowledge of release dynamics is critical to understanding their physiological role in normal and pathological brain function. Investigation into transient neurotransmitter dynamics has largely been hindered due to electrical and material requirements for electrochemical stimulation and recording. Current systems require complex electronics for biasing and amplification and rely on materials that offer limited sensor selectivity and sensitivity. These restrictions result in bulky, tethered, or battery-powered systems impacting behavior and that require constant care of subjects. To overcome these challenges, we demonstrate a fully implantable, wireless, and battery-free platform that enables optogenetic stimulation and electrochemical recording of catecholamine dynamics in real time. The device is nearly 1/10th the size of previously reported examples and includes a probe that relies on a multilayer electrode architecture featuring a microscale light emitting diode (µ-LED) and a carbon nanotube (CNT)-based sensor with sensitivities among the highest recorded in the literature (1264.1 nA µM-1 cm-2). High sensitivity of the probe combined with a center tapped antenna design enables the realization of miniaturized, low power circuits suitable for subdermal implantation even in small animal models such as mice. A series of in vitro and in vivo experiments highlight the sensitivity and selectivity of the platform and demonstrate its capabilities in freely moving, untethered subjects. Specifically, a demonstration of changes in dopamine concentration after optogenetic stimulation of the nucleus accumbens and real-time readout of dopamine levels after opioid and naloxone exposure in freely behaving subjects highlight the experimental paradigms enabled by the platform.

PHIL and Squid Embolization of Cerebral Arteriovenous Malformation: A Retrospective Case Series of 23 Patients.

Precipitating hydrophobic injectable liquid (PHIL; MicroVention, Aliso Viejo, CA, USA) and Squid (Balt, Irvine, CA, USA) are 2 newer liquid embolic agents used in endovascular embolization of cerebral arteriovenous malformation (AVM). This study aims to investigate and compare the effectiveness and safety profile of the 2 newer liquid embolic agents in the embolization of cerebral AVM. This is a retrospective study on all patients diagnosed with cerebral AVM undergoing endovascular embolization with liquid embolic agents PHIL and Squid admitted to the Division of Neurosurgery, Department of Surgery in Prince of Wales Hospital from January 2014 to June 2021. Twenty-three patients with cerebral AVM were treated with 34 sessions of endovascular embolization with either PHIL or Squid (17 sessions each) liquid embolic agents with a male to female ratio of 2.3:1 (male 16; female 7) and mean age of 44.6 (range, 12 to 67). The mean total nidus obliteration rate per session was 57% (range, 5% to 100%). Twenty-one patients (91.3%) received further embolization, stereotactic radiosurgery, or surgical excision after initial endovascular embolization. There were 2 morbidities (1 neurological and 1 non-neurological, 6%) and no mortalities (0%). All patients had static or improvement in modified Rankin Scale at 3 to 6 months at discharge. PHIL and Squid are effective and safe liquid embolic agents for endovascular embolization of cerebral AVM, achieving satisfactory nidal obliteration rates and patient functional outcomes.

A Giant Tumefactive Perivascular Space: A Rare Cause of Obstructive Hydrocephalus and Monoparesis.

Cerebral perivascular spaces (PVSs), otherwise known as Virchow-Robin spaces, are interstitial fluid-filled channels, <2 mm in diameter that form around arterial perforators as they course from the cortex into the brain parenchyma. In contrast, a giant tumefactive PVS is a rare entity comprising of clusters of such channels larger than 15mm resembling a neoplastic process as the name suggests. We report a 55-year-old male who presented with unsteady gait, cognitive decline, and left lower limb weakness for 6 months. Magnetic resonance imaging revealed a noncontrast enhancing multicystic intraaxial lesion of the right mesencephalon-diencephalon junction extending into the anterior third ventricle causing obstructive hydrocephalus. A ventriculoperitoneal shunt was inserted with a complete reversal of his neurological symptoms. Such PVSs can easily be misidentified for a cystic tumor, and their unique radiological features are discussed to prevent unnecessary surgery. We also demonstrate that when they cause hydrocephalus and midbrain compression symptoms cerebrospinal fluid shunting alone can result in excellent outcomes.

Intraventricular urokinase to treat a blocked ventriculoperitoneal shunt in a glioblastoma patient with leptomeningeal spread.

Leptomeningeal spread and hydrocephalus are increasingly recognized as late disease complications of glioblastoma with almost a quarter of patients requiring early cerebrospinal fluid shunting. The neurosurgeon is challenged with maintaining shunt patency when tumor disease progression is rapid and adjuvant oncologic therapy has yet to be initiated. We describe our experience in treating a young female with diffuse glioblastoma leptomeningeal spread and communicating hydrocephalus who had several episodes of shunt obstruction due to intraluminal tumor cell-fibrin deposits. Regular intraventricular instillations of urokinase fibrinolytic therapy not only re-established shunt patency but also contributed to the resolution of her hydrocephalus.

Co-expression of Cytoskeletal Protein Adducin 3 and CD133 in Neurospheres and a Temozolomide-resistant Subclone of Glioblastoma.

BACKGROUND: Glioma stem cells are associated for temozolomide-resistance in glioblastoma. Adducin 3 (ADD3) is a cytoskeletal protein associated with chemoresistance but its role in glioblastoma has not been investigated. MATERIALS AND METHODS: Using an in vitro model of glioblastoma cells with acquired temozolomide resistance (D54-MG-R), the expressions of ADD3 and cancer stem cell markers were compared to those in temozolomide-sensitive glioblastoma cells (D54-MG-S). Immunofluorescence staining was used to investigate the expression patterns of ADD3 and cancer stem cell markers in temozolomide resistance and neurospheres of glioblastoma. RESULTS: Chemoresistant cells were found to have up-regulation of ADD3 and CD133 expression. A sub-population of D54-MG-R cells and glioma neurospheres exhibited coexpression of ADD3 with CD133. CONCLUSION: To our knowledge, this is the first report of a possible link between cytoskeletal protein expression, cancer stem cell phenotype and temozolomide resistance in human glioblastoma. This report lays the foundation for further investigation for ADD3 as a potential biomarker and therapeutic target in temozolomide-resistant glioma cells.

MicroRNA-21 inhibition enhances in vitro chemosensitivity of temozolomide-resistant glioblastoma cells.

BACKGROUND: Glioblastoma multiforme (GBM) is a form of highly malignant brain tumour. Temozolomide (TMZ) is the standard agent for GBM, but TMZ-resistance is common and accounts for many treatment failures. MicroRNA-21 (miR-21) is a non-coding RNA that plays critical roles in many biological processes in cancer, including chemoresistance. We investigated miR-21 expression and the effect of miR-21 inhibition in GBM with acquired TMZ resistance. MATERIALS AND METHODS: Human GBM cell line D54MG was treated with TMZ chronically to develop a chemoresistant subclone. MiR-21 inhibition was achieved by transfection with anti-mir-21 oligonucleotide. RESULTS: Chronic TMZ exposure resulted in acquired TMZ-resistance and elevated miR-21 expression. Concomitant treatment with miR-21 inhibitor and TMZ resulted in a significantly higher apoptotic rate than TMZ treatment alone. CONCLUSION: MiR-21 may have a potential for use as a biomarker of acquired TMZ resistance. MiR-21 inhibition can be further explored as a potential chemotherapy adjunct in the treatment of TMZ-resistant GBM.