Nanoparticles have been emerged as a promising platform to treat different types of tumors due to their ability to transport drugs to target sites while minimizing adverse effects.
Hyaluronan (HA)-grafted lipid-based nanoparticles (LNPs). These LNPs having an ionized lipid were previously shown to be highly effective in delivering small interfering RNAs (siRNAs) into various cell types. LNP’s surface was functionalized with hyaluronan (HA), a naturally occurring glycosaminoglycan that specifically binds the CD44 receptor expressed on GBM cells.
Cohen et al. found that HA-LNPs can successfully bind to glioblastoma GBM cell lines and primary neurosphers of GBM patients. HA-LNPs loaded with Polo-Like Kinase 1 (PLK1) siRNAs (siPLK1) dramatically reduced the expression of PLK1 mRNA and cumulated in cell death even under shear flow that simulate the flow of the cerebrospinal fluid compared with control groups. Next, a human GBM U87MG orthotopic xenograft model was established by intracranial injection of U87MG cells into nude mice. Convection of Cy3-siRNA entrapped in HA-LNPs was performed, and specific Cy3 uptake was observed in U87MG cells. Moreover, convection of siPLK1 entrapped in HA-LNPs reduced mRNA levels by more than 80% and significantly prolonged survival of treated mice in the orthotopic model. Taken together, this results suggest that RNAi therapeutics could effectively be delivered in a localized manner with HA-coated LNPs and ultimately may become a therapeutic modality for GBM 1).
Cy5.5 conjugated MnO nanoparticles for magnetic resonance/near-infrared fluorescence dual-modal imaging of brain gliomas 2).
Solid lipid nanoparticles (SLNs) conjugated with tamoxifen (TX) and lactoferrin (Lf) were applied to carry anticancer carmustine (BCNU) across the blood-brain barrier (BBB) for enhanced antiproliferation against glioblastoma multiforme (GBM). BCNU-loaded SLNs with modified TX and Lf (TX-Lf-BCNU-SLNs) were used to penetrate a monolayer of human brain-microvascular endothelial cells (HBMECs) and human astrocytes and to target malignant U87MG cells. The surface TX and Lf on TX-Lf-BCNU-SLNs improved the characteristics of sustained release for BCNU. When compared with BCNU-loaded SLNs, TX-Lf-BCNU-SLNs increased the BBB permeability coefficient for BCNU about ten times. In addition, TX-BCNU-SLNs considerably promoted the fluorescent intensity of intracellular acetomethoxy derivative of calcein (calcein-AM) in HBMECs via endocytosis. However, the conjugated Lf could only slightly increase the fluorescence of calcein-AM. Moreover, the order of formulation in the inhibition to U87MG cells was TX-Lf-BCNU-SLNs>TX-BCNU-SLNs>Lf-BCNU-SLNs>BCNU-SLNs. TX-Lf-BCNU-SLNs can be effective in infiltrating the BBB and delivering BCNU to GBM for future chemotherapy application 3)
Senders et al., systematically review all clinically tested fluorescent agents for application in fluorescence guided surgery (FGS) for glioma and all preclinically tested agents with the potential for FGS for glioma.
They assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.
The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5 aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.
5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives. 4).
Neurotrauma Management for the Severely Injured Polytrauma Patient
List Price : $129.00
This text addresses many of the questions which occur when medical professionals of various disciplines interact and have different plans and interventions, each with its own valid scientific and/or experience-based rationale: Questions involving tourniquet placement, ideal fluids and volumes for resuscitation, VTE prophylaxis and many other management considerations. Straightforward decisions in the patient with a single diagnosis often conflict when applied to the neurologically injured polytrauma patients.
- Published on: 2017-01-13
- Original language: English
- Number of items: 1
- Dimensions: 10.00″ h x .0″ w x 7.00″ l, .0 pounds
- Binding: Hardcover
- 340 pages
Dr. Ecklund’s primary clinical and research interests include complex spine, cerebrovascular disease and neurotrauma with an emphasis on blast and penetrating injury. He directs a neurotrauma laboratory at the Uniformed Services University, has over 100 publications and abstracts, and has lectured throughout the world. He also has served on multiple oversight and advisory boards for the Veterans Administration, Department of Defense, National Institutes of Health, NATO, Neurotrauma Foundation, and Brain Trauma Foundation.
In a systematic review of stereoelectroencephalography complications, thirty-five major complications (including 4 fatalities) were reported among 4,000 patients (0.8%) implanted with 33,000 electrodes 1).
SEEG has low associated complications, particularly regarding hemorrhage and infection 2).
Serletis et al., published wound infection (0.08%), hemorrhagic complications (0.08%), and a transient neurological deficit (0.04%) in a total of 5 patients (2.5%). One patient (0.5%) ultimately died due to intracerebral hematoma directly ensuing from SEEG electrode placement 3).
In the Cardinale et al., published series the major complication rate was 12 of 500 (2.4%), including 1 death for indirect morbidity. Median entry point localization error was 1.43 mm (interquartile range, 0.91-2.21 mm) with the traditional workflow and 0.78 mm (interquartile range, 0.49-1.08 mm) with the new one (P < 2.2 × 10). Median target point localization errors were 2.69 mm (interquartile range, 1.89-3.67 mm) and 1.77 mm (interquartile range, 1.25-2.51 mm; P < 2.2 × 10), respectively. 4).
Guénot et al had no general or neurologic complication occurred during the procedures. Two transient postprocedure side effects, consisting of paresthetic sensations in the mouth and mild apraxia of the hand, were observed 5).
In 10 patients that underwent this procedure, there were no derived complications 6).
The total complication rate was 4% in One hundred patients that underwent 101 robot-assisted SEEG procedures 7).
In the series of De Almeida et al., bilateral exploration of the temporal lobes has a morbidity rate of approximately 1%. A higher risk of hematomas occurs with the implantation of four or more electrodes in the frontal lobes 8).
Grupo de Trabajo “Neurocirugía y Deporte” de la Sociedad Española de Neurocirugía
II REUNIÓN MEDICINA Y DEPORTE en Almería los días 12 y 13 de enero de 2017.
The traditional way to reach a deep-seated lesion within the brain is through an open craniotomy. While this route is effective at accomplishing the primary goal of accessing the tumor, it’s littered with collateral damage, says Johns Hopkins Hospital neurosurgeon Kaisorn Chaichana.
Assistant Professor of Neurosurgery, Oncology, and Otolaryngology
“It usually requires a big incision, a big opening in the skull, a big opening in the dura,” he says. “As we dissect downward, we’re compromising the white matter the whole time.” The end result, he adds, is substantial blood loss, long hospital stays, long recovery times and an increased risk of damage to brain structures, which can cause neurological deficits.
Enter the minimally invasive tubular retractor, a device that Chaichana has recently incorporated into many of the procedures he’s performed to help mitigate these issues. With a tubular diameter slightly less than a nickel, this retractor allows for less invasive brain surgery by using an obturator with an atraumatic tip to push white matter away instead of cutting it.
During procedures that use this device, Chaichana and his colleagues typically rely on MRI with diffusion tensor imaging data gathered before surgery to guide an interoperative navigation system. Using these data to pinpoint the location of a lesion, the surgeons make a small opening about the size of a silver dollar through the scalp, skull and dura. They then insert the tubular retractor between white matter tracts directly over the tumor.
Once the obdurator is in place, the surgeons can remove an inner metal insert, leaving behind an inner clear sheath. The surgery is performed with an exoscope—a small camera that hovers over the surgical field—and tools to go within the device. Using this protocol, Chaichana and his colleagues can resect entire tumors with minimal disruption to the surrounding brain structures.
This approach is particularly valuable for tumors in eloquent locations, Chaichana says. Treating these tumors using traditional surgical methods would increase the result in motor, language or visual field deficits because of the large dissection of the critical brain matter. However, in the 30 cases he’s already treated using this device over the past year, these functions have been largely preserved. These patients have also had shorter surgeries, significantly less blood loss, shorter hospital stays and quicker recoveries, he adds.
Because of its host of benefits, Chaichana says, he expects that use of this device will grow throughout this field over time.
“With this approach, we can offer patients the same great results as an open resection,” he says, “while also giving them a much greater chance of preserving their neurological function and quality of life.”
At present, Spinal cord injury stem cell therapy is a therapeutic promise in this field of research 1) 2) 3) 4) 5) 6) 7) 8) 9) but still subject to many uncertainties, with significant confusion due to the disparity of protocols, selection of subjects, cell type, dose and routes of administration used. In experimental studies, it is noteworthy that the functional recovery of paraplegic animals after mesenchymal stem cell (MSC) transplantation starts before tissue regeneration occurs to allow the passage of ascending and descending axons. Therefore, it is obvious that after MSC transplantation into injured central nervous system (CNS) must exist various repair processes, including the release of neurotrophic factors by the transplanted stem cells, or the activation of endogenous processes, including the release of neurotrophic factors by the transplanted stem cells, or the activation of endogenous mechanisms of the spinal cord, able to partially restore neurological functions previously abolished 10) 11) 12) 13) 14)15) 16) 17) 18).
Unflammation and toxins released by damaged cells at the site of a spinal injury often cause further harm to surrounding cells. Researchers are developing treatments that reduce inflammation and soak up toxins and free radicals to minimise additional damage.
Spinal cord injuries often damage neurons and the supporting cells that wrap & insulate neurons. Damaging the supporting cells can cause otherwise functional neurons to die. Researchers are studying how stem cells might be used to replace neurons and their supporting cells to greatly improve a patient’s chances for recovering function.
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural stem cells to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NSCs before transplantation are top priorities to overcome.
Liu et al., developed a safe and cost-effective pipeline to generate clinically relevant NSCs. They first isolated cells from patients’ urine and reprogrammed them into iPSCs by non-integrating Sendai virus vectors, and carried out experiments on neural differentiation. NSCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NSCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NSCs, they grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia.
The specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is Liu et al., belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings 19).