Modifying the ICP pulse wave: effects on parenchymal blood flow pulsatility.

Pulsation of the cerebral blood flow (CBF) produces intercranial pressure (ICP) waves. The aim of this study is to determine whether externally modifying ICP pulsatility alters parenchymal blood flow pulsatility. A cardiac-gated inflatable device was inserted in the lateral epidural space of 12 anesthetized canines (canis familiaris) and used to cause reduction, inversion, and augmentation of the ICP pulse.

"Living Well with Chronic Pain": Integrative Pain Management via Shared Medical Appointments.

Objective: To evaluate the effectiveness of a multidisciplinary, nonpharmacological, integrative approach that uses shared medical appointments to improve health-related quality of life and reduce opioid medication use in patients with chronic pain.

Design: This is a retrospective, pre-post review of "Living Well with Chronic Pain" shared medical appointments (August 2016 through May 2018).

Setting: The appointments included eight 3-hour-long visits held once per week at an outpatient wellness facility.

Epidural Oscillating Cardiac-Gated Intracranial Implant Modulates Cerebral Blood Flow.

Background: We have previously reported a method and device capable of manipulating ICP pulsatility while minimally effecting mean ICP.

Objective: To test the hypothesis that different modulations of the intracranial pressure (ICP) pulse waveform will have a differential effect on cerebral blood flow (CBF).

Methods: Using an epidural balloon catheter attached to a cardiac-gated oscillating pump, 13 canine subjects underwent ICP waveform manipulation comparing different sequences of oscillation in successive animals.

Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression.

Glioblastoma is the most lethal primary brain tumor; however, the crosstalk between glioblastoma stem cells (GSCs) and their supportive niche is not well understood. Here, we interrogated reciprocal signaling between GSCs and their differentiated glioblastoma cell (DGC) progeny. We found that DGCs accelerated GSC tumor growth.

Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies.

Novel method for dynamic control of intracranial pressure.

OBJECT Intracranial pressure (ICP) pulsations are generally considered a passive result of the pulsatility of blood flow. Active experimental modification of ICP pulsations would allow investigation of potential active effects on blood and CSF flow and potentially create a new platform for the treatment of acute and chronic low blood flow states as well as a method of CSF substance clearance and delivery. This study presents a novel method and device for altering the ICP waveform via cardiac-gated volume changes.

Mitochondrial control by DRP1 in brain tumor initiating cells.

Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission.

Biocompatibility evaluation of a thermoplastic rubber for wireless telemetric intracranial pressure sensor coating.

This study investigated the biocompatibility of the experimental thermoplastic rubber Arbomatrix(™) that will be used as the protective coating on a novel intracranial pressure (ICP) sensor silicon chip. Arbomatrix(™) was benchmarked against biocompatible commercial silicone rubber shunt tubing in the brain via a rat model with 60-day implant duration. A bare silicon chip was also implanted.

Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression.

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect.

Vascular endothelial growth factor in the CSF of elderly patients with ventriculomegaly: variability, periodicity and levels in drainage responders and non-responders.

Objectives: The aim of this study was to examine lumbar CSF-VEGF levels from elderly patients with ventriculomegaly to evaluate the possible circadian or periodic concentration profile and relevance to the prediction of drainage response.

Methods: Lumbar CSF samples were collected in 1-h interval over 35 h from 22 patients with ventriculomegaly. CSF-VEGF levels were measured to elucidate the possible circadian or periodic concentration profiles.

Hydrodynamics of the Certas™ programmable valve for the treatment of hydrocephalus.

Background: The new Certas™ shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH2O, and an additional "Virtual Off" setting with an opening pressure >400 mmH2O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the "Virtual Off" setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the Certas™ shunt.

Stability analysis of vascular endothelial growth factor in cerebrospinal fluid.

Vascular endothelial growth factor (VEGF) is a promising biological marker and prognostic indicator in many neurological diseases. Although VEGF concentrations in plasma and cerebrospinal fluid (CSF) are increasingly reported, CSF-VEGF stability pre- and during-assay procedures is seldom evaluated. In the current study, we investigated VEGF variability and stability in CSF related to sample preparation, storage, and routine experimental procedures.

VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus.

Chronic hydrocephalus (CH) is often associated with decreased cerebral blood flow (CBF) and oxygen levels. While the exact pathophysiology is not clear, vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) may be involved. Because the choroid plexus (CP) is involved in cerebrospinal fluid (CSF) production and secretes numerous growth factors including VEGF, it is important to understand VEGF/VEGFR-2 levels in the CP-CSF circulatory system.

Dissociation between vascular endothelial growth factor receptor-2 and blood vessel density in the caudate nucleus after chronic hydrocephalus.

Chronic hydrocephalus (CH) is characterized by the presence of ventricular enlargement, decreased cerebral blood flow (CBF), and brain tissue oxygen delivery. Although the underlying pathophysiological role of vascular endothelial growth factor (VEGF) is not clear, ischemic-hypoxic events in CH are known to trigger its release. Previously, we have shown increased VEGF receptor-2 (VEGFR-2) and blood vessel density (BVd) in the hippocampus after CH.

An experimental in-vivo canine model for adult shunt infection.

Background: Detailed human studies of the mechanisms and development of shunt infection in real time are not possible, and we have developed a canine hydrocephalus model to overcome this. The intention of this pilot study was to show that the canine hydrocephalus model could be shunted using conventional "human" shunts, and that a shunt infection could be established so that further studies could then be planned.

Methods: Hydrocephalus was induced in seven dogs (Canis familiaris) by fourth ventricle obstruction.

Chronic hydrocephalus-induced changes in cerebral blood flow: mediation through cardiac effects.

Decreased cerebral blood flow (CBF) in hydrocephalus is believed to be related to increased intracranial pressure (ICP), vascular compression as the result of enlarged ventricles, or impaired metabolic activity. Little attention has been given to the relationship between cardiac function and systemic blood flow in chronic hydrocephalus (CH). Using an experimental model of chronic obstructive hydrocephalus developed in our laboratory, we investigated the relationship between the duration and severity of hydrocephalus and cardiac output (CO), CBF, myocardial tissue perfusion (MTP), and peripheral blood flow (PBF).

Chronic hydrocephalus in adults.

Chronic hydrocephalus is a complex condition, the incidence of which increases with increasing age. It is characterised by the presence of ventricular enlargement in the absence of significant elevations of intracranial pressure. The clinical syndrome may develop either as a result of decompensation of a "compensated" congenital hydrocephalus, or it may arise de novo in adult life secondary to a known acquired disturbance of normal CSF dynamics.

Drug resistance in epilepsy: the role of the blood-brain barrier.

The blood-brain barrier (BBB) is formed by the endothelial cells lining the brain microvessels. Complex tight junctions linking adjacent endothelial cells make brain capillaries around 100 times tighter than peripheral capillaries to small hydrophilic molecules. As a result, drugs required to act in the brain, including anti-epileptic drugs (AEDs), have generally been made lipophilic, and are thus able to cross the brain endothelium via the lipid membranes.