bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombus organization and healing in the swine experimental aneurysm model. Part I. A histological and molecular analysis
Authors: Lee Daniel , Yuki Ichiro , Murayama Yuichi , Chiang Alexander , Nishimura Ichiro , Vinters Harry V. , Wang Chiachien J. , Nien Yih-Lin , Ishii Akira , WU Benjamin M. , Viñuela Fernando 
Published: January 2008

Object
The authors describe the process of thrombus organization in the swine surgical aneurysm model.

Methods
Lateral carotid artery aneurysms with immediately induced thrombosis were created in 31 swine for a time-course study. Aneurysms were evaluated at 1, 3, 7, 14, 30, and 90 days after they were created. Histological analyses included quantitative immunohistochemical studies and evaluation of collagen deposition. Complementary DNA microarray analysis was performed for gene expression profiling. The lists of up- and downregulated genes were cross-matched with lists of genes known to be associated with cytokines or the extracellular matrix. The expression of selected genes was quantified using real-time polymerase chain reaction. Functional clustering was performed with the Expression Analysis Systematic Explorer (EASE) bioinformatics package.

Results
Histological analysis demonstrated leukocyte and macrophage infiltration in the thrombus at Day 3, myofibroblast infiltration at Days 7 to 14, and progressive collagen deposition and contraction thereafter. Tissue organization occurred in a centripetal fashion. A previously undescribed reticular network of connective tissue was observed at the periphery of the aneurysm at Day 3. Macrophages appeared critical to this thrombus organization. A total of 1109 genes were significantly changed from reference time zero during the time course: CXCL14, which produces a monocyte-specific chemokine, was upregulated over 100-fold throughout the time course; IGF1 was upregulated fourfold at Day 7, whereas IGFBP2 was downregulated approximately 50% at Days 7 and 14. Osteopontin (SPP1) upregulation increased from 30-fold at Day 30 to 45-fold at Day 14. The EASE analysis yielded eight functional classes of gene expression.

Conclusions
This investigation provides a detailed histological and molecular analysis of thrombus organization in the swine aneurysm model. The companion study will describe the effect of embolic bioabsorbable polymers on this process.
Efficacy of nonviral gene transfer in the canine brain
Authors: Oh Seunguk , Pluhar G. Elizabeth , McNeil Elizabeth A. , Kroeger Kurt M. , Liu Chunyan , Castro Maria G. , Lowenstein Pedro R. , Freese Andrew , Ohlfest John R. 
Published: January 2008

Object
The purpose of this study was to evaluate the gene transfer capability and tolerability of plasmid DNA/poly-ethylenimine (PEI) complexes in comparison with adenovirus and naked plasmid DNA in the canine brain.

Methods
Plasmid or adenoviral vectors encoding firefly luciferase were injected directly into the cerebral parenchyma of five adult dogs at varying doses and volumes. Serial physical and neurological examinations, as well as blood and cerebrospinal fluid (CSF) analyses, were conducted before and after the surgery for 3 days. Three days after gene delivery, a luciferase activity assay and immunofluorescence analysis were used to test the brain tissue for gene expression.

Results
Injection into the brain parenchyma resulted in gene transfer throughout the cerebrum with every vector tested. Luciferase expression was highest when adenovirus vectors were used. Injection of plasmid DNA/PEI complexes and naked DNA resulted in similar levels of luciferase expression, which were on average 0.5 to 1.5% of the expression achieved with adenovirus vectors. Immunofluorescent microscopy analysis revealed that plasmid DNA/PEI complexes transduced mainly neurons, whereas adenovirus transduced mainly astrocytes. No significant acute side effects or neurological complications were observed in any of the dogs. Mononuclear cell counts significantly increased in the CSF after adenovirus injection and modestly increased after injection of plasmid DNA/PEI complexes, suggesting that a mild, acute inflammatory response occurred in the central nervous system (CNS).

Conclusions
Compared with rodent models that are limited by very small brains, the dog is an excellent preclinical model in which to assess the distribution and safety of emerging gene transfer technologies. In this study, short-term gene transfer was evaluated as a prelude to long-term expression and safety studies. The authors conclude that the viral and nonviral vectors tested were well tolerated and effective at mediating gene transfer throughout a large portion of the canine brain. The nonviral plasmid vectors were less effective than adenovirus, yet they still achieved appreciable gene expression levels. Due to reduced gene transfer efficiency relative to viral vectors, nonviral vectors may be most useful when the expressed protein is secreted or exerts a bystander effect. Nonviral vectors offer an alternative means to genetically modify cells within the CNS of large mammals.
Intraoperative transaneurysmal coil-assisted clip occlusion of a complex anterior communicating artery aneurysm
Authors: Krayenbühl Niklaus , Krisht Ali F. 
Published: January 2008

✓The combination of surgical and endovascular treatment for complex intracranial aneurysms has previously been used in a staged fashion. To perfect the clipping process of a complex anterior communicating artery aneurysm and to avoid a second staged procedure, the authors used a method of direct intraoperative transaneurysmal coil-assisted clip occlusion of the aneurysm.
To the authors' knowledge this is the first time direct intraoperative transaneurysmal coil-assisted clip occlusion has been reported. It should be kept in mind as one of the options to help in complete obliteration of complex intracranial aneurysms.
Intracerebral Hematoma Lysis
Authors: Rohde Veit , Samadani Uzma 
Published: January 2008

Object
Currently no adequate surgical treatment exists for spontaneous intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to deliver therapeutic agents to the local site of the pathological process, thus reducing adverse systemic effects. The authors report the use of stereotactically implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis of ICH in a rabbit model.

Methods
Ethylene vinyl acetate (EVAc) polymers were loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame, and 0.2 ml of clotted autologous blood was injected into the right frontal lobe parenchyma. After 20 minutes, control BSA polymers were stereotactically implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA polymers were implanted in six rabbits. Animals were killed at 3 days, and blood clot volume was assessed.
The pharmacokinetic study showed release of 146 ng of tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the in vivo study, the six animals treated with tPA polymers had a mean (±standard error of the mean [SEM]) thrombus volume of 1.43 ±0.29 mm3 at 3 days, whereas the six animals treated with blank (BSA-only) polymers had a mean (±SEM) thrombus volume of 19.99 ±3.74 mm3 (p <0.001).

Conclusions
Ethylene vinyl acetate polymers release tPA over the course of 3 days. Stereotactic implantation of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded with tPA may be useful clinically for lysis of ICH without the side effects of systemic administration of tPA.
Brachial plexus injuries: outcome following neurotization with intercostal nerve
Authors: Moiyadi Aliasgar Vajihuddin , Devi Bhagavatula Indira , Sivaraman Nair K. P. 
Published: January 2008

Object
Brachial plexus root avulsion injuries, which are devastating, usually result from high-speed accidents. Nerve transfer provides hope for successful treatment of this difficult set of injuries. Nevertheless, the controversies regarding indications, techniques, and outcome of the various available surgical procedures continue.

Methods
A retrospective analysis was performed in 51 patients (43 male and eight female patients) with brachial plexus injuries who underwent neurotization at the authors' institute between 1997 and 2003. Clinical, electrophysiological, and imaging data were used to identify the type and pattern of involvement of the various elements of the plexus. The mean duration of denervation was 6.4 months (range 2–24 months). Outcome was computed in terms of the overall improvement in power of the target muscle as well as the functional usefulness of such recovery.

Results
There were 50 supraclavicular injuries (25 preganglionic, eight postganglionic, and 17 mixed). One patient had an infraclavicular (posterior spinal cord) injury. Pan–brachial plexus injury with a flail upper limb was the most common pattern. Overall, 55 nerves were neurotized—33 musculocutaneous, 18 axillary, and two each for ulnar and radial nerves (47 single and four double neurotizations—by using intercostal nerve donors in the majority of cases. Adequate follow-up data were available in 36 patients (38 nerves) and these were used for the analysis of outcome. Overall, 58.3% of patients had improvement, and of these 62% achieved useful recovery. This accounted for 36% of overall useful recovery. Multiple logistic regression analysis revealed that regardless of age, sex, mode and pattern of injury, and recipient nerve, the duration of denervation showed a trend toward significance that correlated with overall (but not useful) improvement. The critical duration of denervation was 5.5 months.

Conclusions
Neurotization for brachial plexus root avulsion injuries is a viable option. Early detection and intervention (within 5.5 months) leads to a better overall recovery.
Patient outcome after common peroneal nerve decompression
Authors: Humphreys Douglas B. , Novak Christine B. , Mackinnon Susan E. 
Published: January 2008

Object
This study examines common peroneal nerve decompression and its effect on nerve function.

Methods
Fifty-one peroneal nerve decompressions were retrospectively reviewed. All patients were evaluated preoperatively and postoperatively for motor and sensory function of the peroneal nerve as well as for pain.

Results
Postoperatively, 40 (83%) of 48 patients who had preoperative motor weakness had improvement in motor function. Likewise, 23 (49%) of 47 patients who had sensory disturbances and 26 (84%) of 31 patients who had preoperative pain improved after surgical decompression of the peroneal nerve.

Conclusions
Common peroneal nerve decompression is a useful procedure to improve sensation and strength as well as to decrease pain.
Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin
Authors: Mahmood Asim , Lu Dunyue , Qu Changsheng , Goussev Anton , Zhang Zheng Gang , Lu Chang , Chopp Michael 
Published: January 2008

Object
This study was designed to investigate the neuroprotective properties of recombinant erythropoietin (EPO) and carbamylated erythropoietin (CEPO) administered following traumatic brain injury (TBI) in rats.

Methods
Sixty adult male Wistar rats were injured with controlled cortical impact, and then EPO, CEPO, or a placebo (phosphate-buffered saline) was injected intraperitoneally. These injections were performed either 6 or 24 hours after TBI. To label newly regenerating cells, bromodeoxyuridine was injected intraperitoneally for 14 days after TBI. Blood samples were obtained on Days 1, 2, 3, 7, 14, and 35 to measure hematocrit. Spatial learning was tested using the Morris water maze. All rats were killed 35 days after TBI. Brain sections were immunostained as well as processed for the enzyme-linked immunosorbent assay to measure brain-derived neurotrophic factor (BDNF).

Results
A statistically significant improvement in spatial learning was seen in rats treated with either EPO or CEPO 6 or 24 hours after TBI (p < 0.05); there was no difference in the effects of EPO and CEPO. Also, these drugs were equally effective in increasing the number of newly proliferating cells within the dentate gyrus at both time points. A statistically significant increase in BDNF expression was seen in animals treated with both EPO derivatives at 6 or 24 hours after TBI. Systemic hematocrit was significantly increased at 48 hours and 1 and 2 weeks after treatment with EPO but not with CEPO.

Conclusions
These data demonstrate that at the doses used, EPO and CEPO are equally effective in enhancing spatial learning and promoting neural plasticity after TBI.
Endoscopic stent placement for treatment of secondary bilateral occlusion of the Monro foramina following endoscopic third ventriculostomy in a patient with aqueductal stenosis
Authors: Mori Hiroshi , Koike Toshiro , Fujimoto Tsuyoshi , Nishiyama Kenichi , Yoshimura Junichi , Tanaka Ryuichi 
Published: January 2008

✓ Nontumoral bilateral occlusion of the Monro foramina is a rare clinical condition. Treatment includes shunt placement, endoscopic procedures, or both. The authors describe the case of a 22-year-old woman who had previously undergone placement of a ventriculoperitoneal shunt via a right frontal approach for management of triventricular dilation due to aqueductal stenosis. Six years postoperatively she presented with right-sided slit-ventricle syndrome and stenosis of the right Monro foramen, which was treated with an endoscopic third ventriculostomy and fenestration of the septum pellucidum. Two years later she presented with bilateral lateral ventricular dilation. Inspection of the right lateral ventricle with a fiberscope revealed occlusion of the septum pellucidum fenestration; on observation, the right Monro foramen was covered by thick, tough granulation tissue and the left was occluded by thin membranous tissue. Repeated fenestration of the septum pellucidum and left Monro foraminoplasty were therefore performed by perforating this thin tissue. A stent was then introduced into the third ventricle via the right lateral ventricle, the fenestration in the septum pellucidum, and the left Monro foramen.
The authors note that fiberscopes are in general more maneuverable than rigid endoscopes and conclude that they are particularly useful for the treatment of this type of hydrocephalus.
Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging–based finite element analysis
Authors: Trivedi Rikin A. , Li Zhi-Yong , U-King-Im Jean , Graves Martin J. , Kirkpatrick Peter J. , Gillard Jonathan H. 
Published: January 2008

Object
Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses.

Methods
Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted.

Results
There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition.

Conclusions
Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging–based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.
Characteristics and distribution of somatosensory evoked potentials in the subthalamic region
Authors: Kitagawa Mayumi , Murata Jun-Ichi , Uesugi Haruo , Hanajima Ritsuko , Ugawa Yoshikazu , Saito Hisatoshi 
Published: January 2008

Object
The aim of the present study is to evaluate the topographical distribution of somatosensory evoked potentials (SSEPs) in the subthalamic area, including the zona incerta (ZI). Determination of this distribution may help in the correct placement of deep brain stimulation (DBS) leads.

Methods
Intraoperative SSEPs were recorded from contacts of DBS electrodes at 221 sites in 41 patients: three patients with essential tremor and 38 with Parkinson disease who underwent implantation of DBS electrodes for the relief of severe tremor or parkinsonism.

Results
Two distinct SSEPs were recorded in the subthalamic area. One was a monophasic positive wave with a mean latency of 15.8 ± 0.9 msec, which the authors designated subthalamic P16. Using both cephalic and noncephalic references, subthalamic P16 was only recorded in the ventral part of the ZI (mean 6.6 ± 1. 3 mm posterior to the midcommissure point, 4.8 ± 1.2 mm inferior to the anterior commissure–posterior commissure line, and 9.7 ± 0.6 mm lateral to the midline). When bipolar recordings were made, the traces showed a phase reversal at the caudal part of the ZI. The second potential is a positive–negative SSEP recorded throughout the entire subthalamic area. The mean latencies of the initial positive peak and the major negative peak were 13.6 ± 1.1 msec and 16.4 ± 1.1 msec, respectively. Several small notches were superimposed on the peaks, and their amplitudes were largest at the contact close to the medial lemniscus.

Conclusions
The results indicate that intraoperative SSEPs from DBS electrodes are helpful in refining stereotactic targets in the thalamus and subthalamic areas.
Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles
Authors: Szerlip Nicholas J. , Walbridge Stuart , Yang Linda , Morrison Paul F. , Degen Jeffrey W. , Jarrell S. Taylor , Kouri Joshua , Kerr P. Benjamin , Kotin Robert , Oldfield Edward H. , Lonser Russell R. 
Published: January 2008

Object
Despite recent evidence showing that convection-enhanced delivery (CED) of viruses and virus-sized particles to the central nervous system (CNS) is possible, little is known about the factors influencing distribution of these vectors with convection. To better define the delivery of viruses and virus-sized particles in the CNS, and to determine optimal parameters for infusion, the authors coinfused adeno-associated virus ([AAV], 24-nm diameter) and/or feru-moxtran-10 (24 nm) by using CED during real-time magnetic resonance (MR) imaging.

Methods
Sixteen rats underwent intrastriatal convective coinfusion with 4 μl of 35S-AAV capsids (0.5–1.0 × 1014 viral particles/ml) and increasing concentrations (0.1, 0.5, 1, and 5 mg/ml) of a similar sized iron oxide MR imaging agent (ferumoxtran-10). Five nonhuman primates underwent either convective coinfusion of 35S-AAV capsids and 1 mg/ml ferumoxtran-10 (striatum, one animal) or infusion of 1 mg/ml ferumoxtran-10 alone (striatum in two animals; frontal white matter in two). Clinical effects, MR imaging studies, quantitative autoradiography, and histological data were analyzed.

Results
Real-time, T2-weighted MR imaging of ferumoxtran-10 during infusion revealed a clearly defined hypo-intense region of perfusion. Quantitative autoradiography confirmed that MR imaging of ferumoxtran-10 at a concentration of 1 mg/ml accurately tracked viral capsid distribution in the rat and primate brain (the mean difference in volume of distribution [Vd] was 7 and 15% in rats and primates, respectively). The Vd increased linearly with increasing volume of infusion (Vi) (R2 = 0.98). The mean Vd/Vi ratio was 4.1 ± 0.2 (mean ± standard error of the mean) in gray and 2.3 ± 0.1 in white matter (p < 0.01). The distribution of infusate was homogeneous. Postinfusion MR imaging revealed leakback along the cannula track at infusion rates greater than 1.5 μl/minute in primate gray and white matter. No animal had clinical or histological evidence of toxicity.

Conclusions
The CED method can be used to deliver AAV capsids and similar sized particles to the CNS safely and effectively over clinically relevant volumes. Moreover, real-time MR imaging of ferumoxtran-10 during infusion reveals that AAV capsids and similar sized particles have different convective delivery properties than smaller proteins and other compounds.
Neurogenesis in the postnatal human epileptic brain
Authors: González-Martínez Jorge A. , Bingaman William E. , Toms Steven A. , Najm Imad M. 
Published: January 2008

Object
The normal adult human telencephalon does not reveal evidence of spontaneous neuronal migration and differentiation despite the robust germinal capacity of the subventricular zone (SVZ) astrocyte ribbon that contains neural stem cells. This might be because it is averse to accepting new neurons into an established neuronal network, probably representing an evolutionary acquisition to prevent the formation of anomalous neuronal circuits. Some forms of epilepsy, such as malformations of cortical development, are thought to be due to abnormal corticogenesis during the embryonic and early postnatal periods. The role of postnatal architectural reorganization and possibly postnatal neurogenesis in some forms of epilepsy in humans remains unknown. In this study the authors used resected specimens of epileptic brain to determine whether neurogenesis could occur in the diseased tissue.

Methods
The authors studied freshly resected brain tissue obtained in 47 patients who underwent neurosurgical procedures and four autopsies. Forty-four samples were harvested in patients who underwent resection for the treatment of pharmacoresistant epilepsy.

Results
Using organotypic brain slice preparations cultured with 5-bromodeoxyuridine (a marker for cell proliferation), immunohistochemistry, and cell trackers, the authors demonstrate the presence of spontaneous cell proliferation, migration, and neuronal differentiation in the adult human telencephalon that starts in the SVZ and progresses to the adjacent white matter and neocortex in human neocortical pathological structures associated with epilepsy. No cell migration or neuronal differentiation was found in the control group.

Conclusions
The presence of spontaneous neurogenesis associated with some forms of human neocortical epilepsy may represent an erroneous and maladaptive mechanism for neuronal circuitry repair, or it may be an intrinsic part of the pathogenic process.