bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addition of intravenous N-methyl-D-aspartate receptor antagonists to local fibrinolytic therapy for the optimal treatment of experimental intracerebral hemorrhages
Authors: Thiex Ruth , Weis Joachim , Krings Timo , Barreiro Sonia , Yakisikli-Alemi Funda , Gilsbach Joachim M. , Rohde Veit 
Published: January 2008

Object
Fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) is considered a treatment option in patients with deep-seated intracerebral hemorrhage (ICH). Nevertheless, the results of animal experiments have shown that tPA exerts pleiotropic actions in the brain, including regulation of vasoactivity, amplification of calcium conductance by cleavage of the N-methyl-D-aspartate (NMDA) receptor subunit, and activation of metalloproteinases, which increase excitotoxicity, damage the blood–brain barrier, and worsen edema. The authors investigated whether the noncompetitive NMDA receptor antagonist MK801 can be used as an adjuvant therapy in combination with rtPA to attenuate the unfavorable delayed edema formation and inflammation observed following rtPA therapy in an experimental porcine model of ICH.

Methods
Twenty pigs were used in this study; MK801 (0.3 mg/kg) was administered to each pig intravenously immediately after hematoma induction and on the 1st and 3rd day after hematoma induction. Ten of the 20 pigs were randomly assigned to fibrinolytic therapy with rtPA (MK801–tPA group), whereas in the remaining 10 control animals (MK801 group) the hematomas were allowed to follow their natural courses of resorption. The extent of edema formation was evaluated using magnetic resonance (MR) imaging volumetry on Days 0, 4, and 10 after hematoma induction and was compared with histopathological changes found at necropsy. The mean edema volumes in these two groups were also compared with that in the group of nine pigs examined in a preceding experimental series, in which the animals’ hematomas were only treated with rtPA (tPA group).
In the 10 animals in the MK801–tPA group, the mean perihematoma edema volume on MR images had not significantly increased by Day 4 (p < 0.08) or Day 10 (p < 0.35) after hematoma induction. In the 10 animals in the MK801 group, the increase in mean perifocal edema size was significant after 4 days (p < 0.001) and nonsignificant after 10 days (p < 0.09). In the nine animals in the tPA group, the mean edema volume significantly increased by Days 4 (p < 0.002) and 10 (p < 0.03).

Conclusions
As suggested by the reduction in delayed edema volume and the inflammatory response, MK801 modifies the neurotoxic properties of rtPA but not those of blood degradation products. Possibly, fibrinolytic therapy of ICH is more beneficial if combined with agents such as MK801.
Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor
Authors: Sehba Fatima A. , Friedrich Victor , Makonnen Girma , Bederson Joshua B. 
Published: January 2008

Object
Structural changes in brain parenchymal vessels occur within minutes after subarachnoid hemorrhage (SAH). These changes include platelet aggregation, activation of vascular collagenases, and destruction of perivascular collagen IV. Because collagen IV is an important component of the basal lamina, the authors attempted to further define changes in vascular structure (length and luminal diameter) and their relationship to vascular permeability immediately after SAH. In addition, the authors explored whether such alterations were attenuated by administration of a nitric oxide (NO) donor.

Methods
Endovascular perforation was used to induce SAH in rats. Two sets of experiments were performed. The first established changes in vascular structure and permeability (collagen IV and endothelial barrier antigen [EBA] dual immunofluorescence) during the first 24 hours after SAH. In the second, the investigators examined the effects of an NO donor on vascular structure, permeability, and collagenase activity (in situ zymography). In this second study, animals received intravenous infusion of the NO donor S-nitrosoglutathione (GSNO, 1 μM/8 μl/min) 15 minutes after induction of SAH and were killed 3 hours after SAH onset. Controls were naive unoperated animals for the first study and saline-infused SAH animals for the second.
The authors found a time-dependent decrease in area fraction, length, and luminal diameter of collagen IV– and EBA-immunofluorescent vessels after SAH. The greatest change occurred at 3 hours after onset of SAH. Administration of GSNO was associated with striking preservation of collagen IV and EBA immunofluorescence compared with saline treatment. Zymography indicated decreased collagenase activity in GSNO-treated SAH animals compared with saline-treated SAH animals.

Conclusions
These results demonstrate changes in the structure and permeability of brain parenchymal microvessels after SAH and their reversal by treatment with an NO donor.
Survival and invasiveness of astrocytomas promoted by erythropoietin
Authors: Mohyeldin Ahmed , Dalgard Clifton L. , Lu Huasheng , Mcfate Thomas , Tait A. Sasha , Patel Viral C. , Wong Kondi , Rushing Elizabeth , Roy Subhojit , Acs Geza , Verma Ajay 
Published: January 2008

Object
The hypoxia-inducible pleiotropic hormone, erythropoietin (EPO), has recently been found to promote the development and survival of neurons and astrocytes. Since hypoxia has been implicated in the malignant progression of some human cancers, the authors investigated whether EPO signaling influenced the malignant properties of human astrocytoma cells.

Methods
Reverse transcriptase–polymerase chain reaction, Western blot analysis, and immunohistochemical studies were used to measure EPO and its receptor (EPOR). Cell viability, Matrigel invasion assays, metalloprotease assays, EPO neutralizing antibodies, and EPOR overexpression were used to study the biological actions of EPO.
Expression of both EPO and EPOR was observed in the hypoxic regions and invasive margins of glioma specimens obtained at biopsy, and expression of EPOR correlated with the stage of the tumor. The EPOR was also functionally upregulated by hypoxia in cultured glioblastoma multiforme (GBM) cells. Both hypoxia and EPO protected cultured GBM cells from cisplatin cytotoxicity and promoted the invasiveness of GBM cells through Matrigel by potentiating metalloprotease activity. Hypoxia-enhanced cell invasion was attenuated in cells that overexpressed a nonfunctional EPOR.

Conclusions
Hypoxia-inducible autocrine and paracrine EPO signaling participates in the malignant progression of GBMs.
Image-guided convection-enhanced delivery of gemcitabine to the brainstem
Authors: Murad Gregory J. A. , Walbridge Stuart , Morrison Paul F. , Szerlip Nicholas , Butman John A. , Oldfield Edward H. , Lonser Russell R. 
Published: January 2008

Object
To determine if the potent antiglioma chemotherapeutic agent gemcitabine could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution using a surrogate magnetic resonance (MR) imaging tracer, the authors used convection-enhanced delivery to perfuse the primate brainstem with gemcitabine and Gd–diethylenetriamine pentaacetic acid (DTPA).

Methods
Six primates underwent convective brainstem perfusion with gemcitabine (0.4 mg/ml; two animals), Gd-DTPA (5 mM; two animals), or a coinfusion of gemcitabine (0.4 mg/ml) and Gd-DTPA (5 mM; two animals), and were killed 28 days afterward. These primates were observed over time clinically (six animals), and with MR imaging (five animals), quantitative autoradiography (one animal), and histological analysis (all animals). In an additional primate, 3H-gemcitabine and Gd-DTPA were coinfused and the animal was killed immediately afterward.
In the primates there was no histological evidence of infusate-related tissue toxicity. Magnetic resonance images obtained during infusate delivery demonstrated that the anatomical region infused with Gd-DTPA was clearly distinguishable from surrounding noninfused tissue. Quantitative autoradiography confirmed that Gd-DTPA tracked the distribution of 3H-gemcitabine and closely approximated its volume of distribution (mean volume of distribution difference 13.5%).

Conclusions
Gemcitabine can be delivered safely and effectively to the primate brainstem at therapeutic concentrations and at volumes that are higher than those considered clinically relevant. Moreover, MR imaging can be used to track the distribution of gemcitabine by adding Gd-DTPA to the infusate. This delivery paradigm should allow for direct therapeutic application of gemcitabine to brainstem gliomas while monitoring its distribution to ensure effective tumor coverage and to maximize safety.
Subtotal obliteration of cerebral arteriovenous malformations after Gamma Knife surgery
Authors: Yen Chun Po , Varady Peter , Sheehan Jason , Steiner Melita , Steiner Ladislau 
Published: January 2008

Object
Subtotal obliteration of cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS) implies a complete angiographic disappearance of the AVM nidus but persistence of an early filling draining vein, indicating that residual shunting is still present; hence, per definition there is still a patent AVM and the risk of bleeding is not eliminated. The aim of this study was to determine the risk of hemorrhage for patients with subtotal obliteration of AVMs.

Methods
After GKS for cerebral AVMs, follow-up angiography demonstrated a subtotally obliterated lesion in 159 patients. Of these, in 16 patients a subtotally obliterated AVM developed after a second GKS was performed for the partially obliterated lesion. The mean age of these patients was 35.2 years at the time of the diagnosis of subtotally obliterated AVMs. The lesion volumes at the time of initial GKS treatment ranged from 0.1 to 11.5 cm3 (mean 2.5 cm3). The mean peripheral dose used in the 175 GKS treatments was 22.5 Gy (median 23 Gy, range 15–31 Gy). To achieve total obliteration of the AVM, 23 patients underwent a new GKS targeting the proximal end of the early filling vein. The mean peripheral dose given in these cases was 23 Gy (median 24, range 18–25 Gy).
The incidence of subtotally obliterated AVMs was 7.6% from a total of 2093 AVMs treated and in which follow-up imaging was available. The diagnosis of subtotally obliterated AVMs was made a mean of 29.4 months (range 4–178 months) after GKS. The number of patient-years at risk (from the time of the diagnosis of subtotally obliterated AVMs until either the confirmation of a total obliteration of the lesion on angiography or the time of the latest follow-up angio-graphic study that still visualized the early filling vein) was a mean of 3.9 years, ranging from 0.5 to 13.5 years, and a total of 601 patient-years. There was no case of bleeding after the diagnosis of subtotally obliterated AVMs. Of 90 patients who did not undergo further treatment and in whom follow-up angiography studies were available, the same early filling veins still filled in 24 (26.7%), and the subtotally obliterated AVMs were subsequently obliterated in 66 patients (73.3%). In 19 patients who underwent repeated GKS for subtotally obliterated AVMs and in whom follow-up angiography studies were available, the AVMs were obliterated in 15 (78.9%) and remained patent in four (21.1%).

Conclusions
The fact that none of the patients with subtotally obliterated AVMs suffered a rupture is not compatible with the assumption of an unchanged risk of hemorrhage for these lesions, and implies that the protection from re-bleeding in patients with subtotal obliteration is significant. Subtotal obliteration does not necessarily seem to be a stage of an ongoing obliteration. At least in some cases it represents an end point of this process, with no subsequent obliteration occurring. This observation requires further confirmation by open-ended follow-up imaging.
External ventricular drain infections are independent of drain duration: an argument against elective revision
Authors: Lo Cheng H. , Spelman Denis , Bailey Michael , Cooper D. James , Rosenfeld Jeffrey V. , Brecknell John E. 
Published: January 2008

Object
The authors explored the relationship among the duration of external ventricular drainage, revision of external ventricular drains (EVDs), and cerebrospinal fluid (CSF) infection to shed light on the practice of electively revising these drains.

Methods
In a retrospective study of 199 patients with 269 EVDs in the intensive care unit at a major trauma center in Australasia, the authors found 21 CSF infections. Acinetobacter accounted for 10 (48%) of these infections. Whereas the duration of drainage was not an independent predictor of infection, multiple insertions of EVDs was a significant risk factor. Second and third EVDs in previously uninfected patients were more likely to become infected than first EVDs. An EVD infection was initially identified a mean of 5.5 ± 0.7 days postinsertion (standard error of the mean); these data—that is, the number of days—were normally distributed.

Conclusions
This pattern of infection is best explained by EVD-associated CSF infections being acquired by the introduction of bacteria on insertion of the drain rather than by subsequent retrograde colonization. Elective EVD revision would be expected to increase infection rates in light of these results, and thus the practice has been abandoned by the authors' institution.
Prognostic value of the lateral spread response for intraoperative electromyography monitoring of the facial musculature during microvascular decompression for hemifacial spasm
Authors: Kong Doo-Sik , Park Kwan , Shin Byoung-gook , Lee Jeong Ah , Eum Dong-Ok 
Published: January 2008

Object
The authors conducted a large retrospective study in which they evaluated the efficacy of intraoperative electromyography (EMG) monitoring of facial musculature during microvascular decompression (MVD) and assessed the predictive value of the lateral spread response (LSR) as a prognostic indicator for the treatment outcome of hemifacial spasm (HFS).

Methods
The authors undertook intraoperative monitoring during MVD in 300 consecutive patients with HFS. The patients were divided into two groups based on whether the LSR disappeared or persisted following decompression. The mean follow-up period was 35.8 months (range 12–55 months). In 263 (87.7%) of the 300 patients, the LSR was observed during intraoperative facial EMG monitoring. In 230 (87.4%) of these 263 patients, the LSR disappeared following decompression (Group I), and in the remaining 33 patients (12.5%) the LSR persisted despite decompression (Group II). At the postoperative 1-year follow-up visit, there was a significant difference in clinical outcomes between both groups (p < 0.05).

Conclusions
Facial EMG monitoring of the LSR is an effective tool to use when performing complete decompression, and it may be helpful in predicting outcomes.
Endoscopic, endonasal extended transsphenoidal, transplanum transtuberculum approach for resection of suprasellar lesions
Authors: Laufer Ilya , Anand Vijay K. , Schwartz Theodore H. 
Published: January 2008

Object
The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision and a microscope and have reported a significant risk of cerebrospinal fluid (CSF) leakage. The authors report on a series of purely endoscopic endonasal surgeries for resection of suprasellar supradiaphragmatic lesions above a normal-sized sella turcica with a low risk of CSF leakage.

Methods
A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (three tuberculum sellae and two planum sphenoidale meningiomas) and five were post-chiasmal (four craniopharyngiomas and one Rathke cleft cyst). The floor of the planum sphenoidale and the sella turcica was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was performed in only five cases. Complete resection of the lesions was achieved in all but one patient. The pituitary stalk was preserved in all but one patient, whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus (DI). Vision improved postoperatively in all patients with preoperative impairment. Six patients had temporary DI; in five, the DI became permanent. Four patients with craniopharyngiomas required cortisone and thyroid replacement. After a mean follow up of 10 months, there was only one transient CSF leak when a lumbar drain was clamped prematurely on postoperative Day 5.

Conclusions
A purely endoscopic endonasal approach to suprasellar supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leakage is low and lumbar drainage can be avoided. A larger series will be required to validate this approach.
Contribution of Notch signaling activation to human glioblastoma multiforme
Authors: Kanamori Masayuki , Kawaguchi Tomohiro , Nigro Janice M. , Feuerstein Burt G. , Berger Mitchel S. , Miele Lucio , Pieper Russell O. 
Published: January 2008

Object
Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth.

Methods
Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation.

Conclusions
Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy.
Attenuation of experimental subarachnoid hemorrhage–induced cerebral vasospasm by the adenosine A2A receptor agonist CGS 21680
Authors: Lin Chih-Lung , Shih Huei-Chuan , Lieu Ann-Shung , Lee Kung-Shing , Dumont Aaron S. , Kassell Neal F. , Howng Shen-Long , Kwan Aij-Lie 
Published: January 2008

Object
Impaired endothelium-dependent relaxation is present in vasospastic cerebral vessels after subarachnoid hemorrhage (SAH) and may result from deficient production of endothelial nitric oxide synthase (eNOS) or increased production and/or activity of inducible NOS (iNOS). Accumulating evidence demonstrates that adenosine A2A receptors increase the production of NO by human and porcine arterial endothelial cells, which in turn leads to vasodilation. This study was designed to examine the effects of an adenosine A2A receptor agonist, (2(4-[2-carboxyethyl]phenyl)ethylamino)-5′-N-ethylcarboxamidoadenosine (CGS 21680), in the prevention of SAH-induced vasospasm.

Methods
Experimental SAH was induced in Sprague–Dawley rats by injecting 0.3 ml of autologous blood into the cisterna magna of each animal. Intraperitoneal injections of CGS 21680 or vehicle were administered 5 minutes and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging measurements of cross-sectional areas of the basilar artery (BA) 48 hours after SAH. Expression of eNOS and iNOS in the BA was also evaluated.
Prior to perfusion–fixation, there were no significant differences among animals in the control and treated groups in any physiological parameter that was recorded. The CGS 21680 treatment significantly attenuated SAH-induced vasospasm. Induction of iNOS mRNA and protein in the BA by the SAH was significantly diminished by administration of CGS 21680. The SAH-induced suppression of eNOS mRNA and protein was also relieved by the CGS 21680 treatment.

Conclusions
This is the first evidence that adenosine A2A receptor agonism is effective in preventing SAH-induced vasospasm without significant complications. The beneficial effect of adenosine A2A receptor agonists may be, at least in part, related to the prevention of augmented expression of iNOS and the preservation of normal eNOS expression following SAH. Adenosine A2A receptor agonism holds promise in the treatment of cerebral vasospasm following SAH and merits further investigation.
Attenuation of experimental subarachnoid hemorrhage–induced increases in circulating intercellular adhesion molecule–1 and cerebral vasospasm by the endothelin-converting enzyme inhibitor CGS 26303
Authors: Lin Chih-Lung , Kwan Aij-Lie , Dumont Aaron S. , Su Yu-Feng , Kassell Neal F. , Wang Chih-Jen , Wu Shu-Chuan , Kuo Ching-Ling , Huang Ching-Shan , Jeng Arco Y. , Liu Chin-San 
Published: January 2008

Object
Adhesion molecules, including intercellular adhesion molecule–1 (ICAM-1), vascular cell adhesion molecule–1 (VCAM-1), and E-selectin, are important mediators of inflammation, and their levels are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The investigators previously found that CGS 26303 is effective in preventing and reversing arterial narrowing in a rabbit model of SAH. The purpose of the present study was to examine whether levels of adhesion molecules are altered after treatment with CGS 26303 in this animal model.

Methods
New Zealand White rabbits were each injected with 3 ml of autologous blood in the cisterna magna, and intravenous treatment with CGS 26303 (30 mg/kg) was initiated 1 hour later. The compound was subsequently administered at 12, 24, and 36 hours post-SAH. Blood samples were collected at 48 hours post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. After the rabbits had been killed by perfusion–fixation, the basilar arteries (BAs) were removed and sliced, and their cross-sectional areas were measured.
Treatment with CGS 26303 attenuated arterial narrowing after SAH. Morphologically, corrugation of the internal elastic lamina of BAs was prominently observed in the SAH only and vehicle-treated SAH groups, but not in the CGS 26303–treated SAH group or in healthy controls. There were no significant differences in the levels of VCAM-1 among the four groups. The levels of E-selectin were increased in all animals subjected to SAH (those in the SAH only, SAH plus vehicle, and SAH plus CGS 26303 groups) compared with healthy controls (no SAH); however, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and treatment with CGS 26303 reduced ICAM-1 to control levels following SAH.

Conclusions
These results show that ICAM-1 may play a role in mediating SAH-induced vasospasm and that a reduction of ICAM-1 levels after SAH may partly contribute to the antispastic effect of CGS 26303.