Effect of the novel high-affinity glycine-site N-methyl-d-aspartate antagonist ACEA-1021 on 125I-MK-801 binding after subdural hematoma in the rat: an in vivo autoradiographic study

1996 ◽  
Vol 85 (4) ◽  
pp. 655-661 ◽  
Author(s):  
Xiao Di ◽  
Ross Bullock
Keyword(s):  
Nmda Receptor ◽  
Ion Channel ◽  
Subdural Hematoma ◽  
Nmda Antagonist ◽  
Channel Activation ◽  
Content Type ◽  
Mk 801 ◽  
High Affinity ◽  
Fine Print

✓ Acute subdural hematoma (SDH) complicates 20% of severe human head injuries and causes death or severe disability in 60% of these cases, due to brain swelling and high intracranial pressure. Although the mechanisms for these phenomena are unknown, previous studies have implicated excitatory amino acid—mediated mechanisms in both humans and animal models. The authors therefore performed in vivo autoradiography using 125I-MK-801, a high-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, as a tracer to evaluate NMDA ion channel activation spatially and temporally as a factor causing cytotoxic swelling. Acute SDH was induced in 16 anesthetized rats using 0.4 ml autologous venous blood. Fifty microcuries of 125I-MK-801 was injected via an aortic arch cannula 30 minutes after onset of SDH. The effect of a new putatively neuroprotective drug, ACEA-1021, a glycine-specific binding site NMDA antagonist, on 125I-MK-801 binding was tested on five animals. “Nonspecific” 125I-MK-801 binding in the rat brain was assessed by pretreatment with “cold” (nonradiolabeled) MK-801 in five more animals. Four hours later the animals were sacrificed and brain sections were apposed to radiation-detecting high-sensitivity photographic film with precalibrated plastic standards for 4 weeks. A striking and highly significant 1.7- to 4.8-fold increase in 125I-MK-801 binding was seen in the penumbra of viable tissue surrounding the ischemic zone beneath the acute SDH, when compared to contralateral hemisphere binding (p < 0.001). The MK-801 pretreatment markedly reduced 125I-MK-801 uptake in this penumbral zone (4.73 ± 0.36 nCi/mg control vs. 2.85 ± 0.08 nCi/mg cold MK-801; p < 0.0001), indicating that the increased binding in the penumbra of the lesion was due to NMDA ion channel activation. Pretreatment with ACEA-1021 reduced 125I-MK-801 uptake by 28% (3.41 ± 0.26 nCi/mg vs. 4.73 ± 0.36 nCi/mg; p < 0.05), indicating that this agent prevents opening of the NMDA ion channel and, thus, exposure of its receptor for MK-801 binding. These studies show intense foci of penumbral NMDA receptor-mediated ion channel activation after onset of SDH, which is markedly reduced by an NMDA antagonist. Such agents are thus likely to reduce cell swelling after SDH occurs.

Apoptosis following spinal cord injury in rats and preventative effect of N-methyl-d-aspartate receptor antagonist

1999 ◽  
Vol 91 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Shoichi Wada ◽  
Kazunori Yone ◽  
Yasuhiro Ishidou ◽  
Tomonori Nagamine ◽  
Shinji Nakahara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Nmda Receptor ◽  
Content Type ◽  
Mk 801 ◽  
Cord Injury ◽  
Number Of Cells ◽  
Fine Print

Object. The aims of this study were to clarify the histological and histochemical changes associated with cell death in the spinal cord after acute traumatic injury and to examine the role of excitatory amino acid release mediated by N-methyl-d- aspartate (NMDA) receptors. Methods. Following laminectomy, the spinal cord in 70 rats was injured at the T-9 level by applying extradural static weight—compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury (SCI) with paralysis of the lower extremities. The injured rats were killed between 30 minutes and 14 days after injury, and the injured cord was removed en bloc. Rats that received NMDA receptor antagonist (MK-801) were killed at the same time points as those that received saline. The specimens were stained with hematoxylin and eosin, Nissl, and Klüver—Barrera Luxol fast blue and subjected to in situ nick-end labeling, a specific in situ method used to allow visualization of apoptosis. Thirty minutes post-SCI, a large hematoma was observed at the compressed segment. Six hours after injury, large numbers of dead cells that were not stained by in situ nick-end labeling were observed. Between 12 hours and 14 days postinjury, nuclei stained by using the in situ nick-end labeling technique were observed not only at the injury site but also in adjoining segments that had not undergone mechanical compression, suggesting that the delayed cell death was due to apoptosis. The number of cells stained by in situ nick-end labeling was maximum at 3 days postinjury. The results of electron microscopic examination were also consistent with apoptosis. In the MK-801—treated rats, the number of cells stained by in situ nick-end labeling was smaller than in nontreated rats at both 24 hours and 7 days after injury. Conclusions. These findings suggest that NMDA-receptor activation promotes delayed neuronal and glial cell death due to apoptosis.

The contrast-enhanced CT scan in the diagnosis of isodense subdural hematoma

1979 ◽  
Vol 50 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Fong Y. Tsai ◽  
James E. Huprich ◽  
Hervey D. Segall ◽  
James S. Teal
Keyword(s):  
Cerebral Cortex ◽  
Ct Scan ◽  
Subdural Hematoma ◽  
Correct Diagnosis ◽  
Content Type ◽  
Subdural Hematomas ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Enhanced Ct ◽  
Fine Print

✓ The authors review 29 cases of surgically-proven isodense subdural hematomas examined by non-contrast and contrast-enhanced computerized tomography scans. Three types of isodense collections were noted: homogeneous isodense collections, mixed-density collections, and gravitational layering within subdural collections. Contrast enhancement within the cerebral cortex, cortical vessels, and subdural membranes led to the correct diagnosis in each case. Contrast-enhanced scans are essential for the evaluation of isodense subdural hematomas.

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.

Acute subdural hematoma

1982 ◽  
Vol 57 (2) ◽  
pp. 254-257 ◽  
Author(s):  
Henry A. Shenkin
Keyword(s):  
Computerized Tomography ◽  
Subdural Hematoma ◽  
Neurological Status ◽  
Neurological Dysfunction ◽  
Acute Subdural Hematoma ◽  
Consecutive Series ◽  
Content Type ◽  
Subdural Hematomas ◽  
Fine Print

✓ In a consecutive series of 39 cases of acute subdural hematoma (SDH), encountered since computerized tomography diagnosis became available, 61.5% were found to be the result of bleeding from a small cortical artery, 25.6% were of venous origin, 7.7% resulted from cerebral contusions, and 5% were acute bleeds into chronic subdural hematomas. Craniotomy was performed promptly on admission, but there was no difference in survival (overall 51.3%) between patients with arterial and venous bleeds. The only apparent factor affecting survival in this series was the preoperative neurological status: 67% of patients who were decerebrate and had fixed pupils prior to operation died. Of patients with less severe neurological dysfunction, only 20% failed to survive.

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.

Middle meningeal artery embolization for refractory chronic subdural hematoma

2000 ◽  
Vol 93 (4) ◽  
pp. 686-688 ◽  
Author(s):  
Shinya Mandai ◽  
Masaru Sakurai ◽  
Yuzo Matsumoto
Keyword(s):  
Liver Cirrhosis ◽  
Subdural Hematoma ◽  
Therapeutic Approach ◽  
Chronic Subdural Hematoma ◽  
Middle Meningeal Artery ◽  
Artery Embolization ◽  
Content Type ◽  
Meningeal Artery ◽  
Fine Print

✓ The authors present a case of refractory chronic subdural hematoma (CSH) in a 59-year-old man with coagulopathy due to liver cirrhosis. The patient was successfully treated by embolization of the middle meningeal artery after several drainage procedures. This new therapeutic approach to recurrent CSH is discussed.

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.

Angiographic extravasation of contrast medium in acute traumatic subdural hematoma from arterial rupture

1972 ◽  
Vol 37 (2) ◽  
pp. 226-228 ◽  
Author(s):  
Jusuke Ito ◽  
Komei Ueki ◽  
Hisayuki Ishikawa
Keyword(s):  
Contrast Medium ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Subdural Hematoma ◽  
Carotid Angiography ◽  
Content Type ◽  
Arterial Rupture ◽  
Visual Evidence ◽  
Subpial Hemorrhage ◽  
Fine Print

✓ Carotid angiography of a patient with suspected subdural hematoma showed extravasation of the contrast medium from an ascending branch of the middle cerebral artery. The leak was verified at operation. There was no visual evidence of an aneurysm, angioma, subarachnoid or subpial hemorrhage.

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.

Chronic subdural hematoma simulating transient cerebral ischemic attacks

1975 ◽  
Vol 42 (1) ◽  
pp. 101-103 ◽  
Author(s):  
Eldad Melamed ◽  
Slvan Law ◽  
Avinoam Reches ◽  
Abraham Sahar
Keyword(s):  
Subdural Hematoma ◽  
Clinical Picture ◽  
Chronic Subdural Hematoma ◽  
Sensory Deficit ◽  
Transient Ischemic Attacks ◽  
Neurological Manifestations ◽  
Content Type ◽  
Pathophysiological Mechanisms ◽  
Cerebral Ischemic ◽  
Fine Print

✓ A patient is presented in whom chronic subdural hematoma simulated transient ischemic attacks. The neurological manifestations were those of recurrent, transient episodes of expressive dysphasia preceded by focal sensory deficit. Various pathophysiological mechanisms which could have caused the unusual clinical picture are briefly considered.

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