Cerebral arterial spasm

1974 ◽  
Vol 40 (4) ◽  
pp. 451-458 ◽  
Author(s):  
George S. Allen ◽  
Lawrence H. A. Gold ◽  
Shelley N. Chou ◽  
Lyle A. French
Keyword(s):  
Experimental Results ◽  
Arterial Spasm ◽  
Entire Study ◽  
Content Type ◽  
Fine Print

✓ In vivo experiments in dogs demonstrated that physiological concentrations of serotonin, when injected intracisternally, caused cerebral arterial spasm that lasted for at least 3 hours. Comparable spasm was produced by the injection of blood containing approximately the same amount of serotonin. Phenoxybenzamine reversed both the spasm produced by pure serotonin and that produced by blood. A hypothesis of the etiology of cerebral arterial spasm is proposed based on the experimental results of the entire study.

CSF leukotriene C4 following subarachnoid hemorrhage

1988 ◽  
Vol 69 (4) ◽  
pp. 488-493 ◽  
Author(s):  
Pietro Paoletti ◽  
Paolo Gaetani ◽  
Guido Grignani ◽  
Lucia Pacchiarini ◽  
Vittorio Silvani ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Subarachnoid Hemorrhage ◽  
Arterial Spasm ◽  
Lipoxygenase Pathway ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Csf Levels ◽  
Fine Print

✓ Leukotrienes derive from arachidonic acid metabolism via the lipoxygenase pathway and modulate several cellular events. In the central nervous system, leukotrienes are mainly synthesized in the gray matter and in vascular tissues. Their production is enhanced in ischemic conditions and in experimental subarachnoid hemorrhage (SAH). Previous studies have indicated the ability of the leukotrienes C4 and D4 to constrict arterial vessels in vivo and in vitro and have suggested their involvement in the pathogenesis of cerebral arterial spasm. In the present study, the authors measured lumbar and cisternal cerebrospinal fluid (CSF) levels of leukotriene C4 in 48 patients who had suffered aneurysmal SAH. In 12 of the cases, symptomatic and radiological spasm was evident. The mean lumbar CSF level of immunoreactive-like activity of leukotriene C4 (i-LTC4) was significantly higher (p < 0.005) than in control cases, while the cisternal CSF level was higher than the lumbar mean concentration (p < 0.005). Patients presenting with vasospasm had significantly higher levels of i-LTC4 compared to patients without symptomatic vasospasm. This is the first report concerning monitoring of i-LTC4 levels in the CSF after SAH. The results of this study suggest that: 1) metabolism of arachidonic acid via the lipoxygenase pathway is enhanced after SAH; 2) the higher cisternal CSF levels of i-LTC4 may be part of the biological response in the perianeurysmal subarachnoid cisterns after the hemorrhage; and 3) the higher CSF levels of i-LTC4 in patients presenting with vasospasm suggest that a relationship exists between this compound and arterial spasm and/or reflect the development of cerebral ischemic damage.

Invasion of human glioma biopsy specimens in cultures of rodent brain slices: a quantitative analysis

2002 ◽  
Vol 97 (1) ◽  
pp. 169-176 ◽  
Author(s):  
Sophie de Boüard ◽  
Christo Christov ◽  
Jean-Sébastien Guillamo ◽  
Lina Kassar-Duchossoy ◽  
Stéphane Palfi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Brain Slices ◽  
Lower Grade ◽  
Human Glioma ◽  
Newborn Mice ◽  
Content Type ◽  
Biopsy Specimens ◽  
Rodent Brain ◽  
Fine Print

Object. The reliable assessment of the invasiveness of gliomas in vitro has proved elusive, because most invasion assays inadequately model in vivo invasion in its complexity. Recently, organotypical brain cultures were successfully used in short-term invasion studies on glioma cell lines. In this paper the authors report that the invasiveness of human glioma biopsy specimens directly implanted into rodent brain slices by using the intraslice implantation system (ISIS) can be quantified with precision. The model was first validated by the demonstration that, in long-term studies, established glioma cells survive in the ISIS and follow pathways of invasion similar to those in vivo. Methods. Brain slices (400 µm thick) from newborn mice were maintained on millicell membranes for 15 days. Cells from two human and one rodent glioblastoma multiforme (GBM) cell lines injected into the ISIS were detected by immunohistochemistry or after transfection with green fluorescent protein—containing vectors. Preferential migration along blood vessels was identified using confocal and fluorescent microscopy. Freshly isolated (≤ 24 hours after removal) 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate—prelabeled human glioma biopsy specimens were successfully implanted in 19 (83%) of 23 cases, including 12 GBMs and seven lower grade gliomas (LGGs). Morphometric quantification of distance and density of tumor cell invasion showed that the GBMs were two to four times more invasive than the LGGs. Heterogeneity of invasion was also observed among GBMs and LGGs. Directly implanted glioma fragments were more invasive than spheroids derived from the same biopsy specimen. Conclusions. The ISIS combines a high success rate, technical simplicity, and detailed quantitative measurements and may, therefore, be used to study the invasiveness of biopsy specimens of gliomas of different grades.

Administration of interleukin-12 and -18 enhancing the antitumor immunity of genetically modified dendritic cells that had been pulsed with Semliki Forest virus—mediated tumor complementary DNA

2002 ◽  
Vol 97 (5) ◽  
pp. 1184-1190 ◽  
Author(s):  
Ryuya Yamanaka ◽  
Naoki Yajima ◽  
Naoto Tsuchiya ◽  
Junpei Honma ◽  
Ryuichi Tanaka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antitumor Immunity ◽  
Semliki Forest Virus ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Antitumor Effects ◽  
Content Type ◽  
Immunogene Therapy ◽  
Fine Print

Object. Immunogene therapy for malignant gliomas was further investigated in this study to improve its therapeutic efficacy. Methods. Dendritic cells (DCs) were isolated from bone marrow and pulsed with phosphate-buffered saline or Semliki Forest virus (SFV)—mediated 203 glioma complementary (c)DNA with or without systemic administration of interleukin (IL)-12 and IL-18 to treat mice bearing the 203 glioma. To study the immune mechanisms involved in tumor regression, the authors investigated tumor growth of an implanted 203 glioma model in T cell subset—depleted mice and in interferon (IFN) γ—neutralized mice. To examine the protective immunity produced by tumor inoculation, a repeated challenge of 203 glioma cells was given by injecting the cells into the left thighs of surviving mice and the growth of these cells was monitored. The authors demonstrated that the combined administration of SFV-cDNA, IL-12, and IL-18 produced significant antitumor effects against the growth of murine glioma cells in vivo and also can induce specific antitumor immunity. The synergic effects of the combination of SFV-cDNA, IL-12, and IL-18 in vivo were also observed to coincide with markedly augmented IFNγ production. The antitumor effects of this combined therapy are mediated by CD4+ and CD8+ T cells and by NK cells. These results indicate that the use of IL-18 and IL-12 in DC-based immunotherapy for malignant glioma is beneficial. Conclusions. Immunogene therapy combined with DC therapy, IL-12, and IL-18 may be an excellent candidate in the development of a new treatment protocol. The self-replicating SFV system may therefore provide a novel approach for the treatment of malignant gliomas.

Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo

1994 ◽  
Vol 80 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Yasuhiro Matsuda ◽  
Keiichi Kawamoto ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Tumor Volume ◽  
Collagen Gel ◽  
Antitumor Effects ◽  
Histological Changes ◽  
Content Type ◽  
The Relationship ◽  
Fine Print

✓ The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifepristone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.

Intraoperative subcortical stimulation mapping for hemispheric perirolandic gliomas located within or adjacent to the descending motor pathways: evaluation of morbidity and assessment of functional outcome in 294 patients

2004 ◽  
Vol 100 (3) ◽  
pp. 369-375 ◽  
Author(s):  
G. Evren Keles ◽  
David A. Lundin ◽  
Kathleen R. Lamborn ◽  
Edward F. Chang ◽  
George Ojemann ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Motor Deficit ◽  
Motor Deficits ◽  
Tumor Removal ◽  
Entire Study ◽  
Content Type ◽  
Motor Pathways ◽  
Baseline Status ◽  
Subcortical Stimulation ◽  
Fine Print

Object. Intraoperative stimulation mapping of subcortical white matter tracts during the resection of gliomas has become a valuable surgical adjunct that is used to reduce morbidity associated with tumor removal. The purpose of this retrospective analysis was to assess the morbidity and functional outcome associated with this method, thus allowing the surgeon to predict the likelihood of causing a temporary or permanent motor deficit. Methods. In this study, the authors report their experience with intraoperative stimulation mapping to locate subcortical motor pathways in 294 patients who underwent surgery for hemispheric gliomas within or adjacent to the rolandic cortex. Data were collected regarding intraoperative cortical and subcortical stimulation mapping results, along with the patient's neurological status pre- and postoperatively. For patients in whom an additional motor deficit occurred postoperatively, its evolution was examined. Of 294 patients, an additional postoperative motor deficit occurred in 60 (20.4%). Of those 60, 23 (38%) recovered to their preoperative baseline status within the 1st postoperative week. Another 12 (20%) recovered from their postoperative motor deficit by the end of the 4th postoperative week, and 11 more recovered to their baseline status by the end of the 3rd postoperative month. Thus, 46 (76.7%) of 60 patients with postoperative motor deficits regained their baseline function within the first 90 days after surgery. The remaining 14 patients (4.8% of the entire study population of 294) had a persistent motor deficit after 3 months. Patients whose subcortical pathways were identified with stimulation mapping were more prone to develop an additional (temporary or permanent) motor deficit than those in whom subcortical pathways could not be identified (27.5% compared with 13.1%, p = 0.003). This was also true when additional (permanent) motor deficits lasted more than 3 months (7.4% when subcortical pathways were found, compared with 2.1% when they were not found; p = 0.041). Conclusions. In patients with gliomas that are located within or adjacent to the rolandic cortex and, thus, the descending motor tracts, stimulation mapping of subcortical pathways enables the surgeon to identify these descending motor pathways during tumor removal and to achieve an acceptable rate of permanent morbidity in these high-risk functional areas.

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

2000 ◽  
Vol 92 (2) ◽  
pp. 249-254 ◽  
Author(s):  
Roger J. Packer ◽  
Cory Raffel ◽  
Judith G. Villablanca ◽  
Jörg-Christian Tonn ◽  
Stefan E. Burdach ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Herpes Simplex ◽  
Brain Tumors ◽  
Phase I Study ◽  
Retroviral Vector ◽  
Content Type ◽  
Supratentorial Brain Tumors ◽  
Simplex Virus ◽  
Fine Print

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.

Effects of the Ca++-permeable nonselective cation channel blocker LOE 908 on subarachnoid hemorrhage—induced vasospasm in the basilar artery in rabbits

2003 ◽  
Vol 98 (3) ◽  
pp. 561-564 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Tomoh Masaki ◽  
Nobuo Hashimoto
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intravenous Administration ◽  
Basilar Artery ◽  
Channel Blocker ◽  
Autologous Blood ◽  
Content Type ◽  
Dependent Part ◽  
Before And After ◽  
Fine Print

Object. The Ca++ influx into vascular smooth-muscle cells (VSMCs) plays a fundamental role in the development and chronic effects of vasospasm after subarachnoid hemorrhage (SAH). The Ca++-permeable nonselective cation channels (NSCCs) are activated by several endothelium-derived constricting factors such as endothelin 1 (ET-1) and thromboxane A2. Moreover, the receptor-operated Ca++ channel blocker LOE 908 inhibits ET-1—induced extracellular Ca++ influx via NSCCs in the VSMCs of the basilar artery (BA) and the NSCC-dependent part of ET-1—induced vasoconstriction of BA rings. The purpose of the present study was to evaluate the in vivo role of LOE 908 on SAH-induced vasospasm. Methods. Forty-two Japanese white rabbits were assigned to seven groups. Treatment groups consisted of the following: 1) control rabbits without SAH that received a cisternal injection of saline; 2) rabbits with SAH that were subjected to the intravenous administration of saline; 3 through 6) rabbits with SAH that underwent the intravenous administration of 0.01, 0.1, 1, or 10 mg/kg LOE 908, respectively; and 7) rabbits without SAH that underwent the intravenous administration of 10 mg/kg LOE 908. Autologous blood was injected into the cisterna magna. The caliber of the BA was measured on angiographic studies before and after the cisternal injection of autologous blood. The intravenous injection of LOE 908 inhibited the magnitude of an SAH-induced vasosapsm. In addition, the concentration of LOE 908 required to relax vasospasm (1 mg/kg) correlated with that required to block Ca++ influx into VSMCs. Conclusions. The Ca++ channel blocker LOE 908 may inhibit the magnitude of an SAH-induced vasospasm by blocking the influx of Ca++ through NSCCs in rabbit BAs. Blocking the NSCCs may represent a new treatment for cerebral vasospasm after SAH.

Efficacy of LY233053, a competitive glutamate antagonist, in experimental central nervous system ischemia

1992 ◽  
Vol 76 (1) ◽  
pp. 106-110 ◽  
Author(s):  
Kenneth P. Madden ◽  
Wayne M. Clark ◽  
Abha Kochhar ◽  
Justin A. Zivin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Excitatory Amino Acids ◽  
Neurological Damage ◽  
Content Type ◽  
Glutamate Antagonist ◽  
Fine Print

✓ Antagonists of excitatory amino acids appear to serve a neuroprotective role during ischemic conditions in a variety of in vivo and in vitro models. The usefulness of such agents in the clinical setting, however, may be limited by poor central nervous system (CNS) entry and intolerable side effects. The authors report high efficacy in reducing neurological damage and relatively limited side effects of LY233053, a novel competitive glutamate antagonist, in two models of experimental CNS ischemia in the rabbit.

Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer

2005 ◽  
Vol 102 (1) ◽  
pp. 90-97 ◽  
Author(s):  
David Croteau ◽  
Stuart Walbridge ◽  
Paul F. Morrison ◽  
John A. Butman ◽  
Alexander O. Vortmeyer ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Real Time ◽  
Ct Scanning ◽  
Quantitative Autoradiography ◽  
Cerebral White Matter ◽  
Low Molecular Weight ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Fine Print

Object. Convection-enhanced delivery (CED) is increasingly used to distribute therapeutic agents to locations in the central nervous system. The optimal application of convective distribution of various agents requires the development of imaging tracers to monitor CED in vivo in real time. The authors examined the safety and utility of an iodine-based low-molecular-weight surrogate tracer for computerized tomography (CT) scanning during CED. Methods. Various volumes (total volume range 90–150 µ1) of iopamidol (MW 777 D) were delivered to the cerebral white matter of four primates (Macaca mulatta) by using CED. The distribution of this imaging tracer was determined by in vivo real-time and postinfusion CT scanning (≤ 5 days after infusion [one animal]) as well as by quantitative autoradiography (14C-sucrose [all animals] and 14C-dextran [one animal]), and compared with a mathematical model. Clinical observation (≤ 5 months) and histopathological analyses were used to evaluate the safety and toxicity of the tracer delivery. Real-time CT scanning of the tracer during infusion revealed a clearly definable region of perfusion. The volume of distribution (Vd) increased linearly (r2 = 0.97) with an increasing volume of infusion (Vi). The overall Vd/Vi ratio was 4.1 ± 0.7 (mean ± standard deviation) and the distribution of infusate was homogeneous. Quantitative autoradiography confirmed the accuracy of the imaged distribution for a small (sucrose, MW 359 D) and a large (dextran, MW 70 kD) molecule. The distribution of the infusate was identifiable up to 72 hours after infusion. There was no clinical or histopathological evidence of toxicity in any animal. Conclusions. Real-time in vivo CT scanning of CED of iopamidol appears to be safe, feasible, and suitable for monitoring convective delivery of drugs with certain features and low infusion volumes.

The effect of a lipid hydroperoxide of arachidonic acid on the canine basilar artery

1981 ◽  
Vol 54 (3) ◽  
pp. 357-365 ◽  
Author(s):  
Tomio Sasaki ◽  
Susumu Wakai ◽  
Takao Asano ◽  
Takashi Watanabe ◽  
Takaaki Kirino ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Basilar Artery ◽  
Morphological Changes ◽  
Degenerative Change ◽  
Lipid Hydroperoxide ◽  
Second Phase ◽  
Electron Microscopic ◽  
Content Type ◽  
Fine Print

✓ The in vivo spasmogenic capacity of a lipid hydroperoxide (15-hydroperoxy arachidonic acid: 15-HPAA) was studied in a chronic experiment using the dog. The 15-HPAA was injected into the cisterna magna (0.2 or 2 mg emulsified in bovine serum albumin solution). The changes in diameter of the basilar artery were followed by angiography, and the morphological changes were studied by electron microscopy. The cisternal injection of 0.2 mg of 15-HPAA caused a mild constriction of the basilar artery which lasted about 7 hours. The cisternal injection of 2 mg of 15-HPAA caused a biphasic constriction, the initial phase of which was a moderate narrowing lasting about 10 hours. The second phase started on the 2nd or the 3rd day after injection. The intensity of the arterial narrowing was more pronounced in the second phase than in the first. The prolonged secondary constriction of the basilar artery continued until sacrifice on the 7th day after injection. Electron microscopic study revealed a marked degenerative change in the endothelium and myonecrotic changes in the tunica media. The prolonged arterial constriction in the second phase was invariably associated with remarkable degeneration of the endothelium. On the other hand, myonecrotic changes were limited to a small number of smooth-muscle cells. The results of the present study are consonant with the hypothesis that lipid peroxidation associated with lysis of the subarachnoid clot is involved in the genesis of chronic vasospasm in subarachnoid hemorrhage.

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