Trauma-induced tumorigenesis of cells implanted into the rat spinal cord

2003 ◽  
Vol 98 (5) ◽  
pp. 1065-1071 ◽  
Author(s):  
Koichi Hasegawa ◽  
Martin Grumet
Keyword(s):  
Spinal Cord ◽  
Fluorescent Protein ◽  
Tumor Formation ◽  
Hygromycin Resistance ◽  
Rat Spinal Cord ◽  
Gfp Expression ◽  
Content Type ◽  
The Central Nervous System ◽  
Green Fluorescent ◽  
Fine Print

Object. Findings in several clinical cases have suggested a correlation between tumor formation and previous injury to the central nervous system (CNS); however, the relationship between trauma and tumorigenesis has not been investigated well experimentally. In this study the authors provide evidence correlating tumorigenesis with trauma in the rat spinal cord. Methods. A glial cell line, C6R-G/H, which expresses green fluorescent protein (GFP) and hygromycin phosphotransferase (HPT), was implanted into normal and injured rat spinal cords. In all rats in which the cells were implanted into an injured site, locomotor function deteriorated and histological analysis demonstrated glioblastoma multiforme by 6 weeks; tumorigenesis was correlated with a loss of both GFP expression and resistance to hygromycin treatment. In contrast, no evidence of tumor formation was found at 6 weeks in rats in which the cells were implanted into healthy tissue. When C6R-G/H cells were treated with contused spinal cord extract in culture before implantation, they lost GFP expression and hygromycin resistance, and later formed tumors after implantation into normal spinal cord. Conclusions. The findings of this study indicate that trauma can induce tumorigenesis. Implantation of C6R-G/H cells into traumatized spinal cords resulted in their transformation, which was signaled by loss of GFP expression and hygromycin resistance accompanied by tumor formation. Exposure to extracts derived from injured spinal cord produced similar transformation and gene expression changes, as well as tumor formation after such cells were implanted into normal cords. Care, therefore, should be taken when cells are implanted into an injured CNS because of potential mutagenesis due to trauma-induced factors.

The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats

1994 ◽  
Vol 80 (1) ◽  
pp. 97-111 ◽  
Author(s):  
Shlomo Constantini ◽  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Weight Loss ◽  
Ganglioside Gm1 ◽  
Rat Spinal Cord ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Fine Print

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

The natural history of hemangioblastomas of the central nervous system in patients with von Hippel—Lindau disease

2003 ◽  
Vol 98 (1) ◽  
pp. 82-94 ◽  
Author(s):  
John E. Wanebo ◽  
Russell R. Lonser ◽  
Gladys M. Glenn ◽  
Edward H. Oldfield
Keyword(s):  
Spinal Cord ◽  
Natural History ◽  
Mass Effect ◽  
Content Type ◽  
Von Hippel Lindau ◽  
History Of ◽  
The Central Nervous System ◽  
Brainstem Tumors ◽  
Vhl Disease ◽  
Fine Print

Object. The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel—Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. Methods. The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts. Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. Conclusions. In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect—producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.

Capillary hemangioma of the central nervous system

2004 ◽  
Vol 101 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Masamitsu Abe ◽  
Kazuo Tabuchi ◽  
Shin Tanaka ◽  
Akira Hodozuka ◽  
Katsuzo Kunishio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Capillary Hemangioma ◽  
Benign Tumors ◽  
Content Type ◽  
Perifocal Edema ◽  
The Central Nervous System ◽  
The Brain ◽  
Fine Print

Object. Capillary hemangiomas are benign tumors or tumorlike lesions that originate from blood vessels and have rarely been reported to develop in the brain or spinal cord. The authors summarize the clinical and histological features of capillary hemangiomas of the central nervous system (CNS). Methods. The clinical features, imaging characteristics, and outcomes in 10 patients with CNS capillary hemangiomas were reviewed. Histological studies included immunostaining with CD31, α-smooth muscle actin, vascular endothelial growth factor, and Ki-67 antigen. Three patients with lesions in the brain presented with symptoms of increased intracranial pressure or seizures. Seven patients with lesions in the spinal cord presented with progressive sensorimotor disturbances of the lower limbs. Computerized tomography and magnetic resonance imaging demonstrated well-defined, enhancing lesions associated with marked perifocal edema. Angiography demonstrated hypervascular lesions, which have not recurred after resection. In two cases, multiple satellite lesions resolved after the systemic administration of steroid drugs or interferon-α. Histologically, all lesions were consistent with findings of capillary hemangioma of the skin or soft tissues. The CNS lesions differed significantly from other vascular neoplasms, such as hemangioendotheliomas, hemangiopericytomas, and hemangioblastomas. Conclusions. Capillary hemangiomas of the CNS are benign lesions that can be surgically removed and cured without adjuvant therapy.

scholarly journals Malignant lymphoma of the central nervous system presenting with central neurogenic hyperventilation

1992 ◽  
Vol 76 (4) ◽  
pp. 696-700 ◽  
Author(s):  
Yasushi Shibata ◽  
Kotoo Meguro ◽  
Kiyoshi Narushima ◽  
Fumiho Shibuya ◽  
Mikio Doi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Malignant Lymphoma ◽  
Diffuse Infiltration ◽  
Content Type ◽  
The Central Nervous System ◽  
Entire Central Nervous System ◽  
Radiological Studies ◽  
Fine Print

✓ The case is described of a 72-year-old woman who presented with a progressive right hemiparesis and central neurogenic hyperventilation. Pathological and radiological studies revealed diffuse infiltration of a malignant lymphoma into the entire central nervous system and the upper spinal cord. The authors review 12 cases of tumor-induced central neurogenic hyperventilation and discuss the pathophysiology of this condition.

Superficial siderosis of the central nervous system: magnetic resonance imaging and pathological correlation

1993 ◽  
Vol 79 (5) ◽  
pp. 756-760 ◽  
Author(s):  
Anna J. Janss ◽  
Steven L. Galetta ◽  
Andrew Freese ◽  
Eric C. Raps ◽  
Mark T. Curtis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Magnetic Resonance ◽  
Brain Stem ◽  
Superficial Siderosis ◽  
Mr Images ◽  
Content Type ◽  
The Central Nervous System ◽  
Fine Print

✓ The authors report a 32-year-old woman who had undergone repair of an occipital encephalocele in infancy and who experienced a 20-year history of progressive hearing loss and intermittent vertigo. After parturition, she developed a rapidly progressive quadriparesis and brain-stem dysfunction associated with persistent intraventricular and subarachnoid hemorrhage. Serial magnetic resonance (MR) images showed progressive deposition of hemosiderin along the surface of the brain, brain stem, and spinal cord, and enhanced thickened membranes at the site of the original encephalocele repair. Posterior fossa exploration disclosed hemorrhagic membranes, which were resected; despite removal of this tissue, the patient deteriorated and died. Postmortem examination confirmed iron-containing pigment along the meninges, cerebral hemispheres, brain stem, spinal cord, and cranial nerves accompanied by atrophy of the superficial cerebellar cortex. It is concluded that superficial siderosis may accompany encephalocele repair. This is believed to be the first report in the literature of superficial siderosis of the central nervous system to correlate in vivo MR images with autopsy results.

Effect of a calcium channel blocker on posttraumatic spinal cord blood flow

1987 ◽  
Vol 66 (3) ◽  
pp. 423-430 ◽  
Author(s):  
Abhijit Guha ◽  
Charles H. Tator ◽  
Ian Piper
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Whole Blood ◽  
Channel Blocker ◽  
Rat Spinal Cord ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Pressor Agent ◽  
Fine Print

✓ The normal rat spinal cord blood flow (SCBF) has been shown to increase after administration of nimodipine, a calcium channel blocker. The present study investigates the capability of nimodipine to improve SCBF, as measured by the hydrogen clearance technique, after a 53.0-gm clip compression injury to the T-1 segment of the rat spinal cord. The profound drop in mean systemic arterial blood pressure (MSAP) after cervical cord injury precluded any improvement in posttraumatic SCBF by nimodipine alone. Hence, in a randomized controlled study with five rats per group, pressor agents (whole blood, angiotensin, or adrenaline) were infused to maintain MSAP between 100 and 120 mm Hg after injury. Control animals received only a saline infusion. Nimodipine at the optimal dose found in normal animals (1.5 µg/kg/min) was added to the pressor agents. The MSAP and other physiological parameters were measured in rats receiving the pressor agents only and in those receiving pressor agents combined with nimodipine. In rats receiving whole blood, angiotensin, or adrenaline the posttraumatic MSAP improved to between 100 and 120 mm Hg, but there was no improvement in SCBF compared to the saline group. The addition of nimodipine decreased MSAP and SCBF in all groups except those animals also receiving adrenaline, where the MSAP was maintained at 109 ± 5 mm Hg. In these animals a significant increase in posttraumatic SCBF from 16.5 ± 2.1 to 20.2 ± 2.3 ml/100 gm/min (mean ± standard error of the mean) occurred at the site of injury with the addition of nimodipine. The maintenance of an adequate MSAP by a pressor agent was crucial for nimodipine to improve posttraumatic SCBF by its ability to dilate the spinal vascular bed. Adrenalin was the only pressor agent that could fulfill the above criteria, although other pressor agents need to be investigated. Experiments are underway with the combination of adrenaline and nimodipine to further verify these encouraging results demonstrating an improvement in posttraumatic ischemia of the spinal cord.

Isolated intramedullary histiocytosis-X of the cervical spinal cord

1995 ◽  
Vol 83 (4) ◽  
pp. 716-718 ◽  
Author(s):  
Bruce Hamilton ◽  
Edward S. Connolly ◽  
William T. Mitchell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Cervical Spinal Cord ◽  
Histiocytosis X ◽  
Content Type ◽  
First Case ◽  
The Central Nervous System ◽  
Fine Print

✓ Histiocytosis-X is known to involve the central nervous system, but rarely does this disease involve the spinal cord. To the authors' knowledge, this is the first case of isolated intramedullary histiocytosis-X of the spinal cord to be reported.

Primary (granulomatous) angiitis of the central nervous system with multiple aneurysms of spinal arteries

1993 ◽  
Vol 79 (4) ◽  
pp. 603-607 ◽  
Author(s):  
Meow F. Yoong ◽  
Peter C. Blumbergs ◽  
J. Brian North
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Lymphoid Tissue ◽  
Tissue Type ◽  
Subdural Hemorrhage ◽  
Granulomatous Angiitis ◽  
Content Type ◽  
The Central Nervous System ◽  
Fine Print

✓ A 55-year-old woman with primary (granulomatous) angiitis of the central nervous system in association with non-Hodgkin's lymphoma (mucosa-associated lymphoid tissue type) presented with an acute spinal subdural hemorrhage secondary to rupture of one of several fusiform inflammatory aneurysms of the spinal cord radicular arteries. The literature on hemorrhagic complications, aneurysms, and spinal cord involvement in granulomatous angiitis is reviewed. Recognition of granulomatous angiitis is important, as the condition may be responsive to immunosuppressive therapy.

scholarly journals Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques

2021 ◽  
Author(s):  
Emily K Meseck ◽  
Ghiabe Guibinga ◽  
Stephen Wang ◽  
Cameron McElroy ◽  
Eloise Hudry ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Fluorescent Protein ◽  
Brain Regions ◽  
Expression Cassette ◽  
Gfp Expression ◽  
Meso Scale Discovery ◽  
Cynomolgus Macaques ◽  
Spinal Cord Dorsal ◽  
Green Fluorescent

Biodistribution of self-complementary adeno-associated virus-9 (scAAV9)-chicken beta-actin promoter-green fluorescent protein (GFP) was assessed in juvenile cynomolgus macaques infused intrathecally via lumbar puncture or the intracisterna magna (1.0x1013 or 3.0x1013 vg/animal), with necropsy 28 days later. Our results characterized central nervous system biodistribution compared with systemic organs/tissues by droplet digital polymerase chain reaction for DNA and in situ hybridization. GFP expression was characterized by Meso Scale Discovery electrochemiluminescence immunosorbent assay and immunohistochemistry (IHC). Biodistribution was widespread but variable, with vector DNA and GFP expression greatest in the spinal cord, dorsal root ganglia (DRG), and certain systemic tissues (e.g., liver), with low concentrations in many brain regions despite direct cerebrospinal fluid administration. Transduction and expression were observed primarily in perivascular astrocytes in the brain, with a paucity in neurons. Greater GFP expression was observed in hepatocytes, striated myocytes, cardiomyocytes, spinal cord lower motor neurons, and DRG sensory neurons by IHC. These results suggest caution for use of scAAV9-based intrathecal delivery with the current expression cassette as a modality for neurologic diseases that require widespread brain neuronal expression. This capsid/expression cassette combination may be better suited for diseases that express a secreted protein and/or do not require widespread brain neuronal transduction.

Primary spinal melanoma

1987 ◽  
Vol 66 (1) ◽  
pp. 47-49 ◽  
Author(s):  
Theodore C. Larson ◽  
O. Wayne Houser ◽  
Burton M. Onofrio ◽  
David G. Piepgras
Keyword(s):  
Spinal Cord ◽  
Average Duration ◽  
Primary Melanoma ◽  
Duration Of Symptoms ◽  
Content Type ◽  
Average Survival ◽  
The Central Nervous System ◽  
Thoracic Cord ◽  
Cord Lesion ◽  
Fine Print

✓ The records of five patients with primary melanoma of the spinal cord were reviewed. The tumor most frequently presented as an intramedullary middle or lower thoracic cord lesion. The average duration of symptoms before pathological diagnosis was 29 months, and the average survival after laminectomy and radiation therapy was 6 years 7 months. The findings in this series, when compared with those in the literature, suggest that primary spinal melanoma is a more indolent malignancy than previously reported or than melanoma metastatic to the central nervous system.

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