bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth
Authors: McCutcheon Ian E. , Friend Keith E. , Gerdes Tammy M. , Zhang Bing-Mei , Wildrick David M. , Fuller Gregory N. 
Published: May 2009

Object. Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice.Methods. Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (106/10 µl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth.Conclusions. The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.
Modification of a nasal speculum for transsphenoidal surgery
Authors: Miyake Hiroji , Ohta Tomio 
Published: May 2009

✓ The authors modified a Hardy nasal speculum to improve the access to surgical fields and the handling of various instruments during transsphenoidal surgery. A section of the inferior edge of the speculum was cut out 2 cm from its orifice on both sides. The thickness of the tip of the speculum was also reduced. The authors are prepared to operate using a variety of speculum lengths (the distance between the tip and the cutting level), and this length is selected depending on the distance between the anterior wall of the sphenoid sinus and the surface of the gingiva in the individual patient.A modified nasal speculum was used in transsphenoidal surgery for a pituitary adenoma. With use of this device, the protrusion of the speculum above the gingiva was markedly decreased. Because most instruments are inserted into the inferior portion of the speculum orifice, this approach facilitated the handling of all surgical instruments through the modified nasal speculum. The actual surgical field became shallow and wide, and the long surgical instruments that are generally used for transsphenoidal surgery were unnecessary in most cases.
Cognitive outcome following pallidotomy: the influence of side of surgery and age of patient at disease onset
Authors: Kubu Cynthia S. , Grace Gloria M. , Parrent Andrew G. 
Published: May 2009

Object. The authors studied the neuropsychological correlates of stereotactically guided lesioning of the right and left posteroventral globus pallidus internus (GPi) in a prospective series of patients suffering from Parkinson's disease (PD).Methods. Eighteen patients with PD who underwent stereotactically guided lesioning of the GPi (left side in 10 patients and right side in eight) completed neuropsychological evaluations before and after surgery. Patients served as their own controls. Multiple two-by-two repeated-measures analyses of variance were used to assess neuropsychological changes as a function of the side in which lesioning was performed (lesioning on the left side compared with that on the right) and surgery (presurgery compared with postsurgery). Relationships between cognitive variables and patient age at disease onset, age at surgery, and disease duration were examined using a linear regression model.The most striking findings were evident from results of a phonemic word fluency test in which patients in whom a left-sided pallidotomy had been performed achieved a mean performance score that was lower than the score of patients in whom a right-sided pallidotomy had been performed; this score declined even more as a result of surgery. Change in performance on the word fluency test across pre- and postoperative assessments was also related to patient age at onset of PD in those who had undergone left-sided pallidotomy, with patients of an older age at disease onset showing the greatest decline in performance.Conclusions. These preliminary findings indicate that the side on which surgery was performed and patient age at onset of PD are important in the prediction of postoperative cognitive outcome. The findings also indicate that stereotactically guided lesioning of the GPi presents a relatively mild cognitive risk.
Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage
Authors: Juvela Seppo 
Published: May 2009

Object. The pathogenesis of cerebral vasospasm and delayed ischemia after subarachnoid hemorrhage (SAH) seems to be complex. An important mediator of chronic vasospasm may be endothelin (ET), with its powerful and long-lasting vasoconstricting activity. In this study the author investigated the correlation between serial plasma concentrations of ET and ischemic symptoms, angiographically demonstrated evidence of vasospasm, and computerized tomography (CT) findings after aneurysmal SAH.Methods. Endothelin-1 immunoreactivity in plasma was studied in 70 patients with aneurysmal SAH and in 25 healthy volunteers by using a double-antibody sandwich-enzyme immunoassay (immunometric) technique.On the whole, mean plasma ET concentrations in patients with SAH (mean ± standard error of mean, 2.1 ± 0.1 pg/ml) did not differ from those of healthy volunteers (1.9 ± 0.2 pg/ml). Endothelin concentrations were significantly higher (p < 0.05) in patients who experienced delayed cerebral ischemia with fixed neurological deficits compared with those in other patients (post-SAH Days 0–5, 3.1 ± 0.8 pg/ml compared with 2.1 ± 0.2 pg/ml; post-SAH Days 6–14, 2.5 ± 0.4 pg/ml compared with 1.9 ± 0.2 pg/ml). Patients with angiographic evidence of severe vasospasm also had significantly (p < 0.05) elevated ET concentrations (post-SAH Days 0–5, 3.2 ± 0.8 pg/ml; post-SAH Days 6–14, 2.7 ± 0.5 pg/ml) as did those with a cerebral infarction larger than a lacuna on the follow-up CT scan (post-SAH Days 0–5, 3.1 ± 0.8 pg/ml; post-SAH Days 6–14, 2.5 ± 0.4 pg/ml) compared with other patients. Patients in whom angiography revealed diffuse moderate-to-severe vasospasm had significantly (p < 0.05) higher ET levels than other patients within 24 hours before or after angiography (2.6 ± 0.3 compared with 1.9 ± 0.2 pg/ml). In addition, patients with a history of hypertension or cigarette smoking experienced cerebral infarctions significantly more often than other patients, although angiography did not demonstrate severe or diffuse vasospasm more often in these patients than in others.Conclusions. Endothelin concentrations seem to correlate with delayed cerebral ischemia and vasospasm after SAH. The highest levels of ET are predictive of the symptoms of cerebral ischemia and vasospasm, and ET may also worsen ischemia in patients with a history of hypertension. Thus, ET may be an important causal or contributing factor to vasospasm, but its significance in the pathogenesis of vasospasm remains unknown.
Neurosurgical implications of Carney complex
Authors: Watson Joe C. , Stratakis Constantine A. , Bryant-Greenwood Peter K. , Koch Christian A. , Kirschner Lawrence S. , Nguyen Tung , Carney J. Aidan , Oldfield Edward H. 
Published: May 2009

Object. The authors present their neurosurgical experience with Carney complex. Carney complex, characterized by spotty skin pigmentation, cardiac myxomas, primary pigmented nodular adrenocortical disease, pituitary tumors, and nerve sheath tumors (NSTs), is a recently described, rare, autosomal-dominant familial syndrome that is relatively unknown to neurosurgeons. Neurosurgery is required to treat pituitary adenomas and a rare NST, the psammomatous melanotic schwannoma (PMS), in patients with Carney complex. Cushing's syndrome, a common component of the complex, is caused by primary pigmented nodular adrenocortical disease and is not secondary to an adrenocorticotropic hormone-secreting pituitary adenoma.Methods. The authors reviewed 14 cases of Carney complex, five from the literature and nine from their own experience. Of the 14 pituitary adenomas recognized in association with Carney complex, 12 developed growth hormone (GH) hypersecretion (producing gigantism in two patients and acromegaly in 10), and results of immunohistochemical studies in one of the other two were positive for GH. The association of PMSs with Carney complex was established in 1990. Of the reported tumors, 28% were associated with spinal nerve sheaths. The spinal tumors occurred in adults (mean age 32 years, range 18–49 years) who presented with pain and radiculopathy. These NSTs may be malignant (10%) and, as with the cardiac myxomas, are associated with significant rates of morbidity and mortality.Conclusions. Because of the surgical comorbidity associated with cardiac myxoma and/or Cushing's syndrome, recognition of Carney complex has important implications for perisurgical patient management and family screening. Study of the genetics of Carney complex and of the biological abnormalities associated with the tumors may provide insight into the general pathobiological abnormalities associated with the tumors may provide insight into the general pathobiological features of pituitary adenomas and NSTs.
Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats
Authors: Dimeco Francesco , Rhines Laurence D. , Hanes Justin , Tyler Betty M. , Brat Daniel , Torchiana Elena , Guarnieri Michael , Colombo Mario P. , Pardoll Drew M. , Finocchiaro Gaetano , Brem Henry , Olivi Alessandro 
Published: May 2009

Object. Interleukin-12 (IL-12) has potential for the treatment of tumors because it can stimulate an antitumor immune response and possesses antiangiogenic properties. In the study reported here, the authors investigated the therapeutic role of locally delivered IL-12 in a malignant brain tumor model.Methods. After genetically engineering 9L gliosarcoma cells to express IL-12 (9L-IL12 cells), the authors used these cells as a source of locally delivered cytokine. First, they investigated the behavior of these cells, which were implanted with the aid of stereotactic guidance into the rat brain, by using serial magnetic resonance imaging and histopathological examination. Second, they assessed the antitumor efficacy of proliferating, as well as nonproliferating (irradiated), 9L-IL12 cells by implanting these cells in animals challenged by wild-type 9L gliosarcoma (9Lwt) cells. The IL-12 expression in brain regions injected with 9L-IL12 was confirmed by reverse transcription—polymerase chain reaction. Last, the authors explored whether animals treated with 9L-IL12 cells developed an antitumor immunological memory by rechallenging the survivors with a second injection of 9Lwt cells.The authors demonstrated that local delivery of IL-12 into the rat brain by genetically engineered cells significantly prolongs survival time in animals challenged intracranially with a malignant glioma.Conclusions. These findings support continued efforts to refine local delivery systems of IL-12 in an attempt to bring this therapy to clinical trials.
Induction of tolerance against ischemia/reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A
Authors: Toyoda Tomikatsu , Kassell Neal F. , Lee Kevin S. 
Published: May 2009

Object. Inflammatory responses and oxygen free radicals have increasingly been implicated in the development of ischemic brain injury. In some cases, an attenuation of inflammation or free-radical injury can provide tissue protection. Diphosphoryl lipid A (DPL) is a detoxified derivative of a lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595, which is capable of stimulating the immune system without eliciting direct toxic effects. In this study the authors examined the influence of preconditioning with DPL on ischemia/reperfusion injury in rats.Methods. Sprague—Dawley rats were injected intravenously with either DPL or vehicle. Twenty-four hours later, some animals were tested for superoxide dismutase (SOD) activity. Others were subjected to a 3-hour period of focal cerebral ischemia and, after a reperfusion period of 24 hours, were killed. Infarction volume, SOD activity, and myeloperoxidase (MPO) activity were assayed in the postischemic animals.Pretreatment with DPL produced significant reductions in cerebral infarction and MPO activity in the ischemic penumbra. A significant enhancement of basal SOD activity was observed 24 hours after DPL treatment (that is, before ischemia), and a further enhancement of SOD activity was seen in the ischemic penumbra 24 hours after reperfusion.Conclusions. These data provide the first evidence of a neuroprotective effect of preconditioning with DPL in an in vivo model of cerebral ischemia. Although the precise mechanisms through which DPL exerts its neuroprotective influence remain to be established, an inhibition of the complex inflammatory response to ischemia and an enhancement of endogenous antioxidant activity are leading candidates.
Altered diffusion and perfusion in hydrocephalic rat brain: a magnetic resonance imaging analysis
Authors: Massicotte Eric M. , Buist Richard , Del Bigio Marc R. 
Published: May 2009

Object. It can be inferred from data published in the literature that brain compression occurs in the early stages of acute hydrocephalus and that drainage of extracellular waste products is impaired. The authors hypothesized that compression of the cortex would alter water distribution and retard the diffusion of fluid in the hydrocephalic brain.Methods. Proton diffusion, blood perfusion, and T1 and T2 relaxation times were determined in adult rat brain by using magnetic resonance imaging prior to, and 1 and 8 days after induction of hydrocephalus by kaolin injection. Five anatomical regions of interest were studied. The striatum, dorsal cortex, and lateral cortex exhibited decreased T2 and apparent diffusion coefficient (ADC) values but no change in perfusion. Examination of white matter revealed an initial decrease in ADC followed by a significant increase. The T2 relaxation times increased and perfusion decreased progressively between 1 and 8 days after induction of hydrocephalus.Conclusions. Acute experimental hydrocephalus causes compression of gray matter, perhaps associated with reduction in total water, which impairs diffusion of water in the tissue. White matter compression and hypoperfusion precede the development of edema. These findings have importance for understanding the neurochemical changes that occur in hydrocephalic brains.
Neuroprotective effects of citicoline on brain edema and blood—brain barrier breakdown after traumatic brain injury
Authors: Başkaya Mustafa K. , Doğan Aclan , Rao A. Muralikrishna , Dempsey Robert J. 
Published: May 2009

Object. Cytidine 5′-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI.Methods. After anesthesia had been induced in Sprague—Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet—dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight–10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5′-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/kg of CDPC significantly decreased brain edema and BBB breakdown.Conclusions. This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.
Patient presentation, angiographic features, and treatment of strangulation-induced dissection of the internal carotid artery
Authors: Malek Adel M. , Higashida Randall T. , Halbach Van V. , Dowd Christopher F. , Phatouros Constantine C. , Lempert Todd E. , Meyers Philip M. , Smith Wade S. , Stoney Ronald 
Published: May 2009

✓ Domestic violence leading to strangulation by an abusive spouse can cause carotid artery dissection. This phenomenon is rare and has been described in only three previous instances. The authors present their management strategies in three additional cases.Three young women aged 24 to 43 years were victims of manual strangulation committed by their spouses 3 months to 1 year before presentation. Two of the patients suffered delayed cerebral infarctions before presentation and angiography demonstrated focal, mirror-image severe residual stenoses in the high-cervical internal carotid artery (ICA), which were characteristic of a healed chronic dissection; there was no evidence of fibromuscular dysplasia. One of these patients underwent unilateral percutaneous angioplasty with stent placement, and the other underwent bilateral percutaneous angioplasty. Both patients have recovered from their strokes and remain clinically stable at 8 and 20 months posttreatment, respectively. The third patient presented with bilateral ischemic frontal watershed infarctions resulting from an occluded left ICA and a severely narrowed right ICA. Given the extent of the established infarctions, this case was managed with a long-term regimen of anticoagulation medications, and the patient remains neurologically impaired.These cases illustrate the susceptibility of the manually compressed ICA to traumatic injury as a result of domestic violence. They identify bilateral symmetrical ICA dissection as a consistent finding and the real danger of delayed stroke as a consequence of strangulation. Endovascular therapy in which percutaneous angioplasty and/or stent placement are used can be useful in treating residual focal stenoses to improve cerebral perfusion and to lower the risk of embolic or ischemic stroke.
Neural transplantation cannula and microinjector system: experimental and clinical experience
Authors: Mendez Ivar , Hong Murray , Smith Stephen , Dagher Alain , Desrosiers Jacques 
Published: May 2009

✓ The authors present a simple, reliable, and safe system for performing neural transplantation in the human brain. The device consists of a transplantation cannula and microinjector system that has been specifically designed to reduce implantation-related trauma and to maximize the number of graft deposits per injection. The system was evaluated first in an experimental rat model of Parkinson's disease (PD). Animals in which transplantation with this system had been performed showed excellent graft survival with minimal trauma to the brain. Following this experimental stage, the cannula and microinjector system were used in eight patients with PD enrolled in the Halifax Neural Transplantation Program who received bilateral putaminal transplants of fetal ventral mesencephalic tissue. A total of 16 transplantation operations and 64 trajectories were performed in the eight patients, and there were no intraoperative or perioperative complications. Magnetic resonance imaging studies obtained 24 hours after surgery revealed no evidence of tissue damage or hemorrhage. Transplant survival was confirmed by fluorodopa positron emission tomography scans obtained 6 and 12 months after surgery.As neural transplantation procedures for the treatment of neurological conditions evolve, the ability to deliver viable grafts safely will become critically important. The device presented here has proved to be of value in maximizing the number of graft deposits while minimizing implantation-related trauma to the host brain.
Extradural neural axis compartment
Authors: Parkinson Dwight 
Published: May 2009

✓ The lengthy, continuous, slender extradural neural axis compartment (EDNAC), which extends from the coccyx to the orbit, has been not so much discovered as recognized. Through this compartment run arteries, myelinated and unmyelinated nerves, and valveless veins. Adipose tissue is abundant in the orbital and spinal segments, possibly due to movement requirements, although it is very sparse in the skull base segment, the last segment to be recognized as a continuation of the EDNAC, which connects Breschet's veins to the orbit. The lateral sellar compartment (in older terminology, the cavernous sinus) is an enlarged segment of this EDNAC along the skull base connecting the orbit with the extradural space through the superior orbital fissure and down the dorsum to Breschet's veins of the basilar process of the occipital bone. Understanding the continuity of the EDNAC should help the student understand any segment, particularly the skull base.As Batson noted, “Living anatomy is slowly editing and replacing the anatomy of the dead room.”