bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia
Authors: Huh Pil W. , Belayev Ludmila , Zhao Weizhao , Koch Sebastian , Busto Raul , Ginsberg Myron D. 
Published: May 2009

Object. The purpose of this study was to compare the effects of prolonged hypothermia on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats.Methods. Male Sprague—Dawley rats were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-l-lysine through the external carotid artery into the internal carotid artery and the MCA. Two levels of prolonged postischemic cranial hypothermia (32°C and 27°C) and one level of intraischemic cranial hypothermia (32°C) were compared with the ischemic normothermia (37°C) condition. Target cranial temperatures were maintained for 3 hours and then gradually restored to 35°C over an additional 2-hour period. The animals were evaluated using a quantitative neurobehavioral battery of tests before inducing MCA occlusion, during occlusion (at 60 minutes postonset in all rats except those in the intraischemic hypothermia group), and at 24, 48, and 72 hours after reperfusion. The rat brains were perfusion fixed at 72 hours after ischemia, and infarct volumes and brain edema were determined. Both intraischemic and postischemic cooling to 32°C led to similar significant reductions in cortical infarct volume (by 89% and 88%, respectively) and total infarct volume (by 54% and 69%, respectively), whereas postischemic cooling to 27°C produced lesser reductions (64% and 49%, respectively), which were not statistically significant. All three hypothermic regimens significantly lessened hemispheric swelling and improved the neurological score at 24 hours. The authors' data confirm that a high degree of histological neuroprotection is conferred by postischemic cooling to 32°C, which is virtually equivalent to that observed with intraischemic cooling to the same level.Conclusions. These results may be relevant to the design of future clinical trials of therapeutic hypothermia for acute ischemic stroke.
Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure
Authors: Benveniste Helene , Kim Katie R. , Hedlund Laurence W. , Kim John W. , Friedman Allan H. 
Published: May 2009

Object. It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model.Methods. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons.There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups.Conclusions. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.
Intracerebral administration of interleukin-1β and induction of inflammation, apoptosis, and vasogenic edema
Authors: Holmin Staffan , Mathiesen Tiit 
Published: May 2009

Object. The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor—α (TNFα) are produced intracerebrally in brain disorders such as trauma, ischemia, meningitis, and multiple sclerosis. This investigation was undertaken to analyze the effect of intracerebral administration of IL-1β and TNFα on inflammatory response, cell death, and edema development.Methods. Intracerebral microinjections of these cytokines were administered to rats. The animals were killed 24 or 72 hours after the injections, and their brains were analyzed by using deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) with digoxigenin-labeled deoxyuridine triphosphate, immunohistochemical studies, and brain-specific gravity measurement. The IL-1β induced a transient inflammatory response (p < 0.001) and TUNEL staining (p < 0.001), indicating cell death, in intrinsic central nervous system (CNS) cells and infiltrating inflammatory cells. In 73.8 ± 6.77% of the TUNEL-positive cells, small, fragmented nuclei were found. All TUNEL-positive cells expressed the proapoptotic gene Bax, and 69.6 ± 4.6% of the TUNEL-positive cells expressed the antiapoptotic gene Bcl-2; the Bax expression was stronger than the Bcl-2 expression. Taken together, the data indicate that cell death occurred via the apoptotic pathway. The TNFα did not induce inflammation or DNA fragmentation within the analyzed time period. Both IL-1β (p < 0.001) and TNFα (p < 0.01) caused vasogenic edema, as measured by specific gravity and albumin staining. The edematous effect of TNFα persisted 72 hours after injection (p < 0.01), whereas the IL-1β—treated animals had normalized by that time.Conclusions. Intracerebral inflammation, death of intrinsic CNS cells, and vasogenic edema can be mediated by IL-1β, and TNFα can cause vasogenic edema. Suppression of these cytokines in the clinical setting may improve outcome.
Reduced xenograft rejection in rat striatum after pretransplant photodynamic therapy of murine neural xenografts
Authors: Honey Christopher R. , Obochi Modestus O. K. , Shen Hao , Margaron Philippe , Yip Stephen , Levy Julia G. 
Published: May 2009

Object. The goal of this study was to develop a method of reducing neural xenograft rejection by pretreating the graft with photodynamic therapy (PDT).Methods. Xenograft cell suspensions were prepared from fetal mouse mesencephalon, after which they were incubated for 30 minutes with various concentrations of a photosensitizer, verteporfin for injection, and light exposure. The xenograft cell suspensions were injected into the dopamine-depleted striata of 40 hemiparkinsonian rats assigned to different treatment groups. Four weeks after transplantation, xenograft function (determined by methamphetamine-induced rotation) and survival (determined by immunohistochemical staining for murine neurons) were compared. Group 1 animals (xenografts pretreated with 25 ng/ml verteporfin) and Group 3 animals (no verteporfin pretreatment, but daily administration of cyclosporin A) had significantly better xenograft survival and function compared with control animals (no pretreatment with verteporfin). Group 2 animals (xenografts pretreated with 250 ng/ml verteporfin) had no significant improvement.Conclusions. This work demonstrates improved neural xenograft survival and function when using pretransplant PDT of the graft in a rodent model. The potential benefits of this new therapy are its convenience (one pretransplant treatment) and its compatibility with host immunosuppression.
Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo
Authors: Pu Peiyu , Liu Xuwen , Liu Aixue , Cui Jianling , Zhang Yunting 
Published: May 2009

Object. The goal of this study was to evaluate the effect of antisense epidermal growth factor receptor (EGFR) RNA on the growth of rat glioma cells in vitro and in vivo and to determine the feasibility of targeting the EGFR gene for gene therapy in gliomas.Methods. Antisense EGFR complementary (c)DNA was transfected into C6 glioma cells by using lipofectamine. In vitro studies, Southern and Northern blot analyses, in situ hybridization, and immunohistochemical staining were designed to examine the integration and expression of antisense EGFR constructs. The 3′(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay and the average number of argyrophilic nuclear organizer regions (Ag-NORs) were used to evaluate cell proliferation, whereas the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and microscopy were used to observe cell apoptosis. As part of the in vivo studies, parental C6 cells and C6 cells transfected with EGFR antisense cDNA were implanted stereotactically into the right caudate nucleus of Wistar rats (C6-injected animals and transfected C6-injected animals). Rats with well-established cerebral C6 glioma foci were treated intratumorally with either antisense EGFR cDNA or empty-vector DNA by using lipofectamine (treated-C6 and control treated group). The general behavior and survival of the rats, findings on magnetic resonance images of their brains, histopathological changes, proliferation activity, and apoptosis of the cerebral gliomas in each group of rats were examined.Exogenous antisense EGFR cDNA was integrated into the genome of C6 cells and expressed. In clones with a high expression of the antisense construct, there was a dramatic decrease in endogenous EGFR messenger RNA and protein levels, reduced proliferation activity, and induction of apoptosis in vitro. The mean survival time of rats injected with C6 cells was 17.3 days. The mean survival time of rats injected with C6 cells followed by treatment with empty vector in lipofectamine was 15.4 days. Survival time was significantly prolonged in 100% of the rats injected with antisense-transfected C6 cells and in two thirds of the rats injected with C6 cells followed by antisense EGFR cDNA. Magnetic resonance imaging revealed distinct cerebral tumor foci in C6-injected rats and in control rats of the treated group, but none were found in the rats injected with transfected C6 cells. Furthermore, tumor foci disappeared completely in C6-injected rats treated with antisense EGFR cDNA. The cerebral gliomas of the rats treated by injection of antisense EGFR RNA were characterized by reduced proliferation activity and the induction of apoptosis.Conclusions. The results of this study indicate that EGFR plays an important role in the genesis of malignant gliomas. It may, therefore, be an effective target of antisense gene therapy in patients with gliomas.
New concept for the pressure setting of a programmable pressure valve and measurement of in vivo shunt flow performed using microflow meter
Authors: Miyake Hiroji , Ohta Tomio , Kajimoto Yoshinaga , Nagao Kohji 
Published: May 2009

✓ The aim of this study was to establish a standard method for determining the pressure setting of the Codman Hakim valve (CHV) in patients with hydrocephalus.The authors' investigation was twofold. It focused on: 1) the relationships among CHV setting, intracranial pressure (ICP), intraabdominal pressure (IAP), hydrostatic pressure (HP), and perfusion pressure (PP); and 2) the shunt flow in 18 patients with normal-pressure hydrocephalus.With the patient in a sitting position, the pressure environment around the ventriculoperitoneal shunt stabilized when PP became equal to the CHV setting. The lower the CHV setting, the lower the ICP obtained in patients in a sitting position (ICPsit) settled. This indicated the possibility of calculating the CHV setting by the equation CHV setting = HP + ideal ICPsit − IAP, where the ideal ICPsit was estimated to be between −70 and −140 mm H2O. The CHV setting was individually determined for 18 patients by using this method. The ICPsit was controlled at a level equal to the estimated ICPsit in most cases, which supported the rationality of our concept. Shunt flow was intermittent or very low when the patient assumed a supine position and between 200 and 600 µl/minute when the patient was seated.Determining the CHV setting by using the equation CHV setting = HP + ideal ICPsit − IAP was found to be useful when directly measuring HP and IAP in patients and estimating the ideal ICPsit to be between −70 and −140 mm H2O. Postoperative shunt control performed using this method was satisfactory, and shunt complications and the number of CHV resettings were lower than in those published in previous reports.Shunt-flow measurement performed in vivo and in real time by using a microflowmeter should be useful not only in testing the functioning of shunt systems, but also in clarifying the pathophysiology of hydrocephalus.
Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector—producer cells followed by intravenous ganciclovir administration
Authors: Packer Roger J. , Raffel Cory , Villablanca Judith G. , Tonn Jörg-Christian , Burdach Stefan E. , Burger Klaus , LaFond Deborah , McComb J. Gordon , Cogen Philip H. , Vezina Gilbert , Kapcala Leonard P. 
Published: May 2009

Object. The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors.Methods. After optimal repeated tumor resection, multiple injections of murine vector—producing cells shedding murine replication—defective retroviral vectors coding the herpes simplex virus thymidine kinase type 1 (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector-producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSV-Tk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2–15 years). Treated brain tumors included seven malignant gliomas, two ependymomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings.Conclusions. This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector—producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.
Efficacy of transluminal angioplasty for the management of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Authors: Polin Richard S. , Coenen Volker A. , Hansen Carolyn Apperson , Shin Peter , Baskaya Mustafa K. , Nanda Anil , Kassell Neal F. 
Published: May 2009

Object. Transluminal angioplasty has become a widely used adjunct therapy to medical management of symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH). Despite anecdotal reports of universal, angiographically confirmed reversal of vasospasm and high rates of clinical improvement, no rigorous examination of the efficacy of this procedure has been conducted. In this study the authors assess the efficacy of the aforementioned procedure.Methods. Thirty-eight patients enrolled as part of the North American trial of tirilazad in aneurysmal SAH underwent transluminal angioplasty for symptomatic cerebral vasospasm. Fifty-three percent of these patients showed good recovery or moderate disability based on their 3-month Glasgow Outcome Scale score.Among the 38 patients who underwent angioplasty, the severity and type of vasospasm, use of papaverine in addition to balloon angioplasty, timing of treatment, and dose of study drug did not have an effect on the outcome. The results of their neurological examinations improved in only four of the 38 patients immediately after the procedure. A conditional logistic regression analysis was performed in which these patients were compared with individuals matched for age, sex, dose of study drug, admission neurological grade, and modified Glasgow Coma Scale score at the time of angioplasty. No effect on favorable outcomes was found for this procedure.Conclusions. Transluminal cerebral angioplasty is very effective in reversing angiographically confirmed vasospasm, and anecdotal reports of its clinical utility are numerous. However, in this report the authors conclude that its superiority to medical management for symptomatic cerebral vasospasm is questionable.
Clinical outcomes after carotid endarterectomy: comparison of the use of regional and general anesthetics
Authors: Papavasiliou Achilles K. , Magnadottir Hulda B. , Gonda Tamas , Franz Douglas , Harbaugh Robert E. 
Published: May 2009

Object. The authors analyzed their series of carotid endarterectomies (CEAs), which were performed after administration of either a general or regional anesthetic, to determine whether the choice of anesthetic affected patients' clinical outcomes and length of hospital stay.Methods. A series of 803 consecutive CEAs performed between July 1990 and February 1999 was reviewed. Cases were analyzed for patient demographics, comorbid medical states, and perioperative complications. Contingency-table statistical analysis was used to compare the incidence of comorbid medical states and perioperative complications between patients who underwent CEA in which either a regional or general anesthetic was used. Student's t-test was used to compare the length of hospital stay and mean patient age.A regional anesthetic was used for 632 CEAs, and a general anesthetic was used for 171 operations. There were no statistically significant intergroup differences in demographics or comorbid medical states. The incidence of perioperative stroke and death did not differ significantly between the regional (2.7%) and the general anesthetic groups (2.3%). However, the incidence of nonneurological, nonfatal complications was significantly less in the regional anesthetic (1.6%) than in the general anesthetic group (14 .6%, p < 0.0001). Patients undergoing CEA in which a regional anesthetic was used had a significantly lower incidence of cardiopulmonary complications (myocardial infarction and postoperative intubation), cervical complications (neck hematomas and cranial nerve injuries), and urological complications (urinary retention) than patients who underwent surgery after receiving a general anesthetic.Conclusions. Patients undergoing CEA in which a regional anesthetic was used had significantly fewer nonneurological, nonfatal complications, particularly cardiopulmonary complications, than similar patients surgically treated after induction of general anesthesia.
Marked inhibition of glioblastoma target cell tumorigenicity in vitro by retrovirus-mediated transfer of a hairpin ribozyme against deletion-mutant epidermal growth factor messenger RNA
Authors: Halatsch Marc-Eric , Schmidt Ursula , Bötefür Ingolf C. , Holland James F. , Ohnuma Takao 
Published: May 2009

Object. The goal of this study was to evaluate the activity of certain hairpin ribozymes against deletion-mutant epidermal growth factor receptor (ΔEGFR) messenger (m)RNA in glioblastomas multiforme (GBMs). A distinct 801-bp deletion mutation associated with amplification of the EGFR gene is present in a large subgroup of primary GBMs and confers enhanced tumorigenicity in vivo. As a result of the deletion mutation, the fusion junction of the gene is created directly upstream of a GTA triplet, which is subsequently transcribed into a ribozyme target codon (GUA).Methods. In attempts to intercept ΔEGFR gene expression at the mRNA level, the authors designed three different hairpin ribozymes derived from the negative strands of satellite RNAs in tobacco ringspot virus, chicory yellow mottle virus (sCYMV1), and arabis mosaic virus against this target and evaluated their efficiency and specificity in a cell-free system. The sCYMV1, identified as the most active anti-ΔEGFR hairpin ribozyme motif, was cloned into the retroviral plasmid N2A+tRNAimet. High-titer recombinant retrovirus-containing supernatants (> 105 colony-forming units/ml) derived from an amphotropic GP+envAM 12 packaging cell line transfected with the N2A+tRNAimet-anti-ΔEGFR-sCYMV1 construct were used to introduce the sCYMV1 hairpin ribozyme into U-87MG.ΔEGFR glioblastoma cells, which overexpress exogenous ΔEGFR. Using a virus/target cell ratio of 40:1 in the absence of drug selection, the ribozyme transfer resulted in a greater than 90% reduction of ΔEGFR mRNA levels, a 69% inhibition of ΔEGFR-mediated proliferation advantage, and a greater than 95% decrease of colony formation in soft agar under relative serum starvation conditions in vitro; transfer of a control mutant ribozyme that was rendered incapable of cleaving its target yielded none of these effects.Conclusions. These findings indicate that the anti-ΔEGFR-sCYMV1 hairpin ribozyme is capable of specifically inhibiting the expression of ΔEGFR and reversing the ΔEGFR-associated malignant phenotype of GBM cells. This strategy may constitute a promising gene therapy approach for a molecularly defined subgroup of GBMs.