John Bringas - Academia.edu (original) (raw)

Papers by John Bringas

Neuroscience Letters, May 1, 1993

Neurosurgery, Dec 1, 1993

Brain retraction is required for adequate exposure during many intracranial procedures. The incid... more Brain retraction is required for adequate exposure during many intracranial procedures. The incidence of contusion or infarction from overzealous brain retraction is probably 10% in cranial base procedures and 5% in intracranial aneurysm procedures. The literature on brain retraction injury is reviewed, with particular attention to the use of intermittent retraction. Intraoperative monitoring techniques--brain electrical activity, cerebral blood flow, and brain retraction pressure--are evaluated. Various intraoperative interventions--anesthetic agents, positioning, cerebrospinal fluid drainage, operative approaches involving bone resection or osteotomy, hyperventilation, induced hypotension, induced hypertension, mannitol, and nimodipine--are assessed with regard to their effects on brain retraction. Because brain retraction injury, like other forms of focal cerebral ischemia, is multifactorial in its origins, a multifaceted approach probably will be most advantageous in minimizing retraction injury. Recommendations for operative management of cases involving significant brain retraction are made. These recommendations optimize the following goals: anesthesia and metabolic depression, improvement in cerebral blood flow and calcium channel blockade, intraoperative monitoring, and operative exposure and retraction efficacy. Through a combination of judicious retraction, appropriate anesthetic and pharmacological management, and aggressive intraoperative monitoring, brain retraction should become a much less common source of morbidity in the future.

Neurosurgery, Mar 1, 1994

Magnetic Resonance in Medicine, Nov 11, 2013

Molecular Therapy, Dec 1, 2003

Experimental Neurology, Oct 1, 2000

Japanese Journal of Neurosurgery, 2007

Alzheimers & Dementia, Jul 1, 2014

Neuro-oncology, Nov 1, 2019

Journal of Neurosurgery, Sep 1, 2020

Journal of Magnetic Resonance Imaging, Aug 7, 2012

Methods in molecular biology, 2016

Gene therapy has emerged as a potential avenue of treatment for many neurological disorders. Tech... more Gene therapy has emerged as a potential avenue of treatment for many neurological disorders. Technological advances in imaging techniques allow for the monitoring of real-time infusions into the brain of rodents, nonhuman primates, and humans. Here, we discuss the use of magnetic resonance imaging (MRI) as a tool in the delivery of adeno-associated viral (AAV) particles into brain of nonhuman primates.

Neurosurgery, Jul 1, 2011

Real-time convection-enhanced delivery (RCD) of adeno-associated viral vectors by co-infusion of ... more Real-time convection-enhanced delivery (RCD) of adeno-associated viral vectors by co-infusion of gadoteridol allows T1 magnetic resonance imaging (T1 MRI) prediction of areas of subsequent gene expression. The use of T2 MRI in RCD is less developed. In addition, the effect of flushing a dead-space volume on subsequent distribution of a therapeutic agent is not known. The value of T2 MRI in RCD was investigated by comparing distribution volumes of saline with immediately after T1 RCD of gadoteridol and by comparing T2, T1, and transgene distribution patterns after viral vector RCD. Adult nonhuman primates underwent saline infusion/T2 acquisition, immediately followed by gadoteridol infusion/T1 acquisition in the putamen and brainstem. Distribution volumes and spatial patterns were analyzed. Gadoteridol and adeno-associated virus encoding human aromatic l-amino acid decarboxylase (AAV2-hAADC) were co-infused under alternating T2/T1 acquisition in the thalamus, and hyperintense areas were compared with areas of subsequent transgene expression. Ratios of distribution volume to infusion volume were similar between saline and gadoteridol RCD. Spatial overlap correlated well between T2 and T1 images. The second infusate followed a spatiotemporal pattern similar to that of the first, filling the target area before developing extra-target distribution. Areas of human L-amino acid decarboxylase expression correlated well with areas of both T1 and T2 hyperintensity observed during RCD. Accuracy of cannula placement and initial infusate distribution may be safely determined by saline infusion without significantly altering the subsequent distribution of the tracer agent. T2 RCD provides detection of intraparenchymal convection- enhanced delivery in the uninjured brain and may predict subsequent distribution of a transgene after viral vector infusion.

Journal of Neuro-oncology, Nov 1, 2009

Journal of Neurosurgery, May 1, 2008

Object Many factors relating to the safety and efficacy of convection-enhanced delivery (CED) int... more Object Many factors relating to the safety and efficacy of convection-enhanced delivery (CED) into intracranial tumors are poorly understood. To investigate these factors further and establish a more clinically relevant large animal model, with the potential to investigate CED in large, spontaneous tumors, the authors developed a magnetic resonance (MR) imaging–compatible system for CED of liposomal nanoparticles into the canine brain, incorporating real-time MR imaging. Additionally any possible toxicity of liposomes containing Gd and the chemotherapeutic agent irinotecan (CPT-11) was assessed following direct intraparenchymal delivery. Methods Four healthy laboratory dogs were infused with liposomes containing Gd, rhodamine, or CPT-11. Convection-enhanced delivery was monitored in real time by sequential MR imaging, and the volumes of distribution were calculated from MR images and histological sections. Assessment of any toxicity was based on clinical and histopathological evaluation. Convection-enhanced delivery resulted in robust volumes of distribution in both gray and white matter, and real-time MR imaging allowed accurate calculation of volumes and pathways of distribution. Results Infusion variability was greatest in the gray matter, and was associated with leakage into ventricular or subarachnoid spaces. Complications were minimal and included mild transient proprioceptive deficits, focal hemorrhage in 1 dog, and focal, mild perivascular, nonsuppurative encephalitis in 1 dog. Conclusions Convection-enhanced delivery of liposomal Gd/CPT-11 is associated with minimal adverse effects in a large animal model, and further assessment for use in clinical patients is warranted. Future studies investigating real-time monitored CED in spontaneous gliomas in canines are feasible and will provide a unique, clinically relevant large animal translational model for testing this and other therapeutic strategies.

Stereotactic and Functional Neurosurgery, 2011

Cancer Research, Oct 1, 2004

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent activator of... more Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent activator of cell death, preferentially killing neoplastic cells over normal cells, the efficacy of TRAIL for the treatment of glioma might be limited due to cellular resistance and, importantly, poor distribution after systemic administration. TRAIL and temozolomide (TMZ) were recently shown to have a synergistic antitumor effect against U87MG glioma cells in vitro. Convection-enhanced delivery (CED) can effectively distribute TRAIL protein throughout a brain tumor mass. In this study, we evaluated CED of TRAIL, alone and in conjunction with systemic TMZ administration, for antitumor efficacy. CED of TRAIL demonstrated safe and effective distribution in both normal brain and a U87MG intracranial xenograft model. Individually, both CED of TRAIL and systemic TMZ administration prolonged survival in tumor-bearing rats. However, the combination of these two treatments was significantly more effective than either treatment alone. CED of TRAIL in conjunction with systemic TMZ treatment is a promising strategy for the treatment of malignant gliomas.

Journal of Neurosurgery, Nov 1, 2005

Object-Clinical application of the convection-enhanced delivery (CED) technique is currently limi... more Object-Clinical application of the convection-enhanced delivery (CED) technique is currently limited by low infusion speed and reflux of the delivered agent. The authors developed and evaluated a new step-design cannula to overcome present limitations and to introduce a rapid, reflux-free CED method for future clinical trials. Methods-The CED of 0.4% trypan blue dye was performed in agarose gel to test cannula needles for distribution and reflux. Infusion rates ranging from 0.5 to 50 l/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macaca fascicularis) by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Results of agarose gel studies showed reflux-free infusion with high flow rates using the stepdesign cannula. Data from the study in rats confirmed the agarose gel findings and also revealed increasing tissue damage at a flow rate above 5-l/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. Conclusions-The authors developed a new step-design cannula for CED that effectively prevents reflux in vivo and maximizes the distribution of agents delivered in the brain. Data in the present study show reflux-free infusion with a constant volume of distribution in the rat brain over a broad range of flow rates. Reflux-free delivery of liposomes into nonhuman primate brain was also established using the cannula. This step-design cannula may allow reflux-free distribution and shorten the duration of infusion in future clinical applications of CED in humans.

Archives of Toxicology, 2018