Reduced xenograft rejection in rat striatum after pretransplant photodynamic therapy of murine neural xenografts

2000 ◽  
Vol 92 (1) ◽  
pp. 127-131 ◽  
Author(s):  
Christopher R. Honey ◽  
Modestus O. K. Obochi ◽  
Hao Shen ◽  
Philippe Margaron ◽  
Stephen Yip ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Light Exposure ◽  
Cell Suspensions ◽  
Rat Striatum ◽  
Content Type ◽  
Xenograft Rejection ◽  
Treatment Groups ◽  
Group 2 ◽  
And Function ◽  
Fine Print

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.

Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy

2003 ◽  
Vol 98 (5) ◽  
pp. 1040-1044 ◽  
Author(s):  
Bettina Pfausler ◽  
Heinrich Spiss ◽  
Ronny Beer ◽  
Andreas Kampfl ◽  
Klaus Engelhardt ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Trough Level ◽  
Once Daily ◽  
Content Type ◽  
Treatment Groups ◽  
Efficacious Treatment ◽  
Group 2 ◽  
Vancomycin Level ◽  
Fine Print ◽  
Group 1

Object. Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study. Methods. Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five (median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 ± 0.4 µg/ml in Group 1 and 565.58 ± 168.71 µg/ml 1 hour after vancomycin application in Group 2 (mean ± standard deviation). Vancomycin levels above the recommended trough level of 5 µg/ml in CSF were never reached in Group 1, whereas in Group 2 they were below the trough level (3.74 ± 0.66 µg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained. Conclusions. Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

Implantation of xenografts into parkinsonian rat brain after portal venous administration of xenogeneic donor spleen cells

2001 ◽  
Vol 94 (5) ◽  
pp. 775-781 ◽  
Author(s):  
Hiroshi Takeuchi ◽  
Masahide Yoshikawa ◽  
Seiji Kanda ◽  
Masahiro Nonaka ◽  
Fumihiko Nishimura ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Immunological Tolerance ◽  
Ultraviolet B ◽  
Rotational Behavior ◽  
Spleen Cells ◽  
Content Type ◽  
Group 3 ◽  
Group 2 ◽  
And Function ◽  
Fine Print

Object. The purpose of the present study was to examine the effect of pretransplantation portal venous immunization with ultraviolet B (UVB)—treated donor spleen cells on neural xenograft transplantation. Methods. Cells from a murine catecholaminergic cell line derived from the B6/D2 F1 mouse, CATH.a, were used as a xenograft. Thirty hemiparkinsonian rats were divided into three different treatment groups. Group 1 received saline in the dopamine-denervated striatum; Group 2 received xenograft cells; and Group 3 received portal venous administration of UVB-irradiated B6/D2 F1 splenocytes 7 days before receiving xenograft cells. Xenograft function was determined by reviewing apomorphine-induced rotation at 2-week intervals, and xenograft survival was examined at 4 and 12 weeks after transplantation by immunohistochemical staining for murine tyrosine hydroxylase (THase). Rotational behavior was improved in both xenograft-transplanted groups (Groups 2 and 3); however, the animals in Group 3 displayed a significantly reduced rotational behavior compared with Group 2. In Group 2, many inflammatory cells and a few THase-positive cells were found at the graft sites 4 weeks after transplantation. In Group 3, however, a large number of THase-positive cells were found with few inflammatory cells. The THase-positive cells disappeared in the Group 2 rats at 12 weeks, but remained in Group 3 animals. In Group 3 rats proliferation of spleen cells in a mixed lymphocyte reaction was suppressed in a donor-specific fashion. Conclusions. This work demonstrates improved neural xenograft survival and function by pretransplantation portal venous immunization with UVB-irradiated xenogeneic donor splenocytes. On the basis of these findings, the authors suggest the possibility of creating donor-specific immunological tolerance in the brain by administration of xenogeneic donor lymphocytes via the portal vein.

Evaluation of brain-stem dysfunction following severe fluid-percussion head injury to the cat

1991 ◽  
Vol 74 (2) ◽  
pp. 270-277 ◽  
Author(s):  
Katsuji Shima ◽  
Anthony Marmarou
Keyword(s):  
Brain Stem ◽  
Content Type ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Brain Stem Injury ◽  
Group 2 ◽  
High Level ◽  
Subarachnoid Hemorrhages ◽  
Fine Print ◽  
Group 1

✓ The degree of brain-stem dysfunction associated with high-level fluid-percussion injury (3.0 to 3.8 atm) was investigated in anesthetized cats. Measurements were made of the animals' intracranial pressure (ICP), pressure-volume index (PVI), far-field brain-stem auditory evoked responses (BAER's), and cerebral blood flow (CBF). The animals were classified into two groups based on the severity of neuropathological damage to the brain stem after trauma: Group 1 had mild intraparenchymal and subarachnoid hemorrhages and Group 2 had severe intraparenchymal and subarachnoid hemorrhages. The ICP values in Group 1 were insignificantly lower than those in Group 2, while the PVI values in Group 2 were clearly lower (p < 0.05). Immediately after the injury, peaks II, III, and IV of the BAER's demonstrated a transitory and marked suppression. One Group 1 and two Group 2 animals showed the disappearance of peak V. In Group 1, the latencies of peak II, III, and IV gradually increased until 60 to 150 minutes postinjury, then returned to 95% of baseline value at 8 hours; however, the animals in Group 2 showed poor recovery of latencies. Two hours after brain injury, the CBF decreased to 40% of the preinjury measurement in both groups (p < 0.001). In contrast to Group 2, the CBF in Group 1 returned to 86.8% of the preinjury measurement by 8 hours following the injury. Changes in PVI, BAER, and CBF correlated well with the degree of brain-stem injury following severe head injury'- These data indicate that high-level fluid-percussion injury (> 3.0 atm) is predominantly a model of brain-stem injury.

No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia

2000 ◽  
Vol 93 (5) ◽  
pp. 835-844 ◽  
Author(s):  
Thomas Westermaier ◽  
Stefan Zausinger ◽  
Alexander Baethmann ◽  
Hans-Jakob Steiger ◽  
Robert Schmid-Elsaesser
Keyword(s):  
Mild Hypothermia ◽  
Artery Occlusion ◽  
Burst Suppression ◽  
Moderate Hypothermia ◽  
Sprague Dawley ◽  
Doppler Flowmetry ◽  
Content Type ◽  
Treatment Groups ◽  
Cerebral Artery Occlusion ◽  
Fine Print

Object. Mild-to-moderate hypothermia is increasingly used for neuroprotection in humans. However, it is unknown whether administration of barbiturate medications in burst-suppressive doses—the gold standard of neuroprotection during neurovascular procedures—provides an additional protective effect under hypothermic conditions. The authors conducted the present study to answer this question.Methods. Thirty-two Sprague—Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion and randomly assigned to one of four treatment groups: 1) normothermic controls; 2) methohexital treatment (burst suppression); 3) induction of mild hypothermia (33°C); and 4) induction of mild hypothermia plus methohexital treatment (burst suppression). Local cerebral blood flow was continuously monitored using bilateral laser Doppler flowmetry and electroencephalography. Functional deficits were quantified and recorded during daily neurological examinations. Infarct volumes were assessed histologically after 7 days. Methohexital treatment, mild hypothermia, and mild hypothermia plus methohexital treatment reduced infarct volumes by 32%, 71%, and 66%, respectively, compared with normothermic controls. Furthermore, mild hypothermia therapy provided the best functional outcome, which was not improved by additional barbiturate therapy.Conclusions. The results of this study indicate that barbiturate-induced burst suppression is not required to achieve maximum neuroprotection under mild hypothermic conditions. The magnitude of protection afforded by barbiturates alone appears to be modest compared with that provided by mild hypothermia.

Biomechanical properties of expander compared with conventional screws

2002 ◽  
Vol 97 (3) ◽  
pp. 346-349 ◽  
Author(s):  
Aziz Rassi-Neto ◽  
Antonio Shimano
Keyword(s):  
Maximum Load ◽  
Biomechanical Properties ◽  
Biomechanical Study ◽  
Intergroup Difference ◽  
Content Type ◽  
Significant Difference ◽  
Group 2 ◽  
The Comparative Study ◽  
Screw Group ◽  
Fine Print

Object. A pullout strength biomechanical study was performed in 20 fresh swine vertebral bodies in which titanium expander (Group 1) and conventional screws (Group 2) were placed. Methods. The screws were inserted into the anterosuperior portion of the anterior spine, and assessment was performed after application of loads. The expander screw is composed of two parts: 1) a cover with an external portion comprising tight thin threads; and 2) a compact internal screw inserted through the cover that allows expansion. In the comparative study between the screws in Groups 1 and 2 maximum load was assessed, and the intergroup difference was significant (p = 0.00001 [t-test]); regarding load at the elasticity threshold, a significant difference was also observed (p = 0.0063). With regard to rigidity (stiffness), there was a tendency in both groups toward significance (p = 0.069). With regard to absorbed energy in the elastic phase, statistical analysis showed a significant intergroup difference (p = 0.00439). The expander screw showed a greater load-bearing capacity than the conventional screw. Adhesion to bone in relation to the applied load and displacement was greater (significant tendency) in the expander screw group than in the conventional screw group. Conclusions. The expander screws exhibited a greater capacity to absorb energy in the elastic phase. They adhered better to bone, were easy to insert, and, if necessary, were simple to remove.

Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery

2002 ◽  
Vol 97 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Arun P. Amar ◽  
William T. Couldwell ◽  
Joseph C. T. Chen ◽  
Martin H. Weiss
Keyword(s):  
Prolactin Level ◽  
Serum Prolactin ◽  
Surgical Removal ◽  
Consecutive Series ◽  
Cure Rate ◽  
Content Type ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

Object. Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of “recurrent” tumors. Methods. Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (≤ 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome. Conclusions. Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.

A novel rat model for the study of intraosseous metastatic spine cancer

2005 ◽  
Vol 2 (3) ◽  
pp. 303-307 ◽  
Author(s):  
Ajay Mantha ◽  
Federico G. Legnani ◽  
Carlos A. Bagley ◽  
Gary L. Gallia ◽  
Ira Garonzik ◽  
...  
Keyword(s):  
Rat Model ◽  
Breast Adenocarcinoma ◽  
Rank Test ◽  
Functional Score ◽  
Histopathological Analysis ◽  
Sham Operation ◽  
Content Type ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

Object. Although metastatic spinal disease constitutes a significant percentage of all spinal column tumors, an accessible and reproducible animal model has not been reported. In this study the authors describe the technique for creating an intraosseous spinal tumor model in rats and present a functional and histological analysis. Methods. Eighteen female Fischer 344 rats were randomized into two groups. Group 1 animals underwent a transabdominal exposure and implantation of CRL-1666 breast adenocarcinoma into the L-6 vertebral body (VB). Animals in Group 2 underwent a sham operation. Hindlimb function was tested daily by using the Basso-Beattie-Bresnahan scale. Sixteen days after tumor implantation, animals were killed and their spines were removed for histological assessment. Statistical analysis was performed using the Wilcoxon signed-rank test. By Day 15 functional analysis showed a significant decrease in motor function in Group 1 animals (median functional score 2 of 21) compared with Group 2 rats (median functional score 21 of 21) (p = 0.0217). The onset of paraparesis in Group 1 occurred within 14 to 16 days of surgery. Histopathological analysis showed tumor proliferation through the VB and into the spinal canal, with marked osteolytic activity and spinal cord compression. Conclusions. Analysis of these findings demonstrates the consistency of tumor growth in this model and validates the utility of functional testing for onset of paresis. This new rat model allows for the preclinical evaluation of novel therapeutic treatments for patients harboring metastatic spine disease.

Prognostic significance of magnetic resonance imaging in the acute phase of cervical spine injury

1992 ◽  
Vol 76 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Dale M. Schaefer ◽  
Adam E. Flanders ◽  
Jewell L. Osterholm ◽  
Bruce E. Northrup
Keyword(s):  
Cervical Spine ◽  
Mr Imaging ◽  
Prognostic Significance ◽  
Spinal Segment ◽  
Content Type ◽  
Group 3 ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

✓ Fifty-seven patients with acute cervical spine injuries and associated major neurological deficit were examined within 2 weeks of injury by magnetic resonance (MR) imaging. All patients had abnormal scans, indicating intramedullary lesions. This study was undertaken to determine if the early MR imaging pattern had a prognostic relationship to the eventual neurological outcome. Three different MR imaging patterns were observed in these patients: 21 patients had patterns characteristic of intramedullary hematoma (Group 1); 17 had intramedullary edema over more than one spinal segment, but no hemorrhage (Group 2); and 19 had restricted zones of intramedullary edema involving one spinal segment or less (Group 3). The neurological state was determined using standard motor index scores at admission and at follow-up examination. Characteristically, the patients in Group 1 had admission motor scores significantly lower than the other two groups. At follow-up examination, the median percent motor recovery was 9% for Group 1, 41% for Group 2, and 72% for Group 3. These studies suggest that the MR imaging pattern observed in the acutely injured human spinal cord has a prognostic significance in the final outcome of the motor system. It is only when an accurate prognosis can be given at the outset that useful treatment data might be collected for homogeneous injury groups, and accurately based long-term planning made for the best patient care.

Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury

2005 ◽  
Vol 2 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Ahmet Çolak ◽  
Alper Karaoǧlan ◽  
Şeref Barut ◽  
Sibel Köktürk ◽  
Aysşenur Iǧdem Akyildiz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Rat Model ◽  
Caspase 9 ◽  
Content Type ◽  
Cord Injury ◽  
Group 3 ◽  
Group 2 ◽  
Fine Print

Object. Apoptosis is considered one of the most significant mechanisms in the pathogenesis of neuronal damage after spinal cord injury (SCI). This form of cell death occurs via mediators known as caspases. The aim of this study was to evaluate the neuroprotective effect of the caspase-9 inhibitor, z-LEHD-fmk, in a rat model of spinal cord trauma. Methods. Fifty-four Wistar albino rats were studied in the following three groups of 18 animals each: sham-operated controls (Group 1); trauma-only controls (Group 2); and trauma combined with z-LEHD-fmk—treated animals (0.8 µM/kg; Group 3). Spinal cord injury was produced at the thoracic level by using the weight-drop technique. Responses to SCI and the efficacy of z-LEHD-fmk treatment were determined on the basis of terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick—end labeling staining and light and electron microscopy findings in cord tissue at 24 hours and 7 days posttrauma. Six rats from each group were also assessed for functional recovery at 3 and 7 days after SCI. This was conducted using the inclined-plane technique and a modified version of the Tarlov motor grading scale. At 24 hours postinjury, light microscopic examination of Group 2 tissue samples showed hemorrhage, edema, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. Those obtained in Group 3 rats at this stage showed similar features. At 24 hours postinjury, the mean apoptotic cell count in Group 2 was significantly higher than that in Group 3 (90.25 ± 2.6 and 50.5 ± 1.9, respectively; p < 0.05). At 7 days postinjury, the corresponding mean apoptotic cell counts were 49 ± 2.1 and 17.7 ± 2.6, also a significant difference (p < 0.05). Electron microscopy findings confirmed the occurrence of programmed cell death in different cell types in the spinal cord and showed that z-LEHD-fmk treatment protected neurons, glia, myelin, axons, and intracellular organelles. Conclusions. Examination of the findings in this rat model of SCI revealed that apoptosis occurs not only in neurons and astrocytes but also in oligodendrocytes and microglia. Furthermore, immediate treatment with the caspase-9 inhibitor z-LEHD-fmk blocked apoptosis effectively and was associated with better functional outcome. More in-depth research of the role of programmed cell death in spinal cord trauma and further study of the ways in which caspases are involved in this process may lead to new strategies for treating SCI.

Cognitive functioning in long-term survivors of high-grade glioma

1994 ◽  
Vol 80 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Yvonne M. Archibald ◽  
Diane Lunn ◽  
Lesley A. Ruttan ◽  
David R. Macdonald ◽  
Rolando F. Del Maestro ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
High Grade Glioma ◽  
High Grade ◽  
Content Type ◽  
Group 2 ◽  
Long Term Survivors ◽  
Disease Free ◽  
Fine Print ◽  
Group 1

✓ In a pilot study, two groups of patients with malignant glioma underwent sequential neuropsychological evaluations after successful tumor treatment. Group 1 included nine patients treated from 1981 to 1985; all patients received irradiation and eight underwent chemotherapy. The baseline neuropsychological assessment was performed 1 to 63 months after tumor diagnosis, with follow-up evaluations at irregular intervals over the next 3 to 7 years. Six patients in Group 1 exhibited impairment on most measures at baseline; subsequently, two patients developed profound cognitive impairment. Initially, three patients functioned in the average range on most tasks; thereafter, two deteriorated on one measure each. Group 2 was ascertained prospectively and included 16 patients treated from 1985 to 1987, all of whom received irradiation and chemotherapy. The first evaluation was performed 18 months after diagnosis, then every 6 months for 2 years, and then yearly. Compared to a control group, those in Group 2 had significant cognitive impairment at baseline. Cognitive performance did not change over the next 12 months in 10 patients who remained free of tumor, but within 2 years of baseline testing, deterioration on specific tasks was evident in two of seven disease-free survivors. When last tested, five of six disease-free survivors had deteriorated on one or more measures. Unlike Group 1, severe global cognitive impairment was not seen, perhaps because Group 2 was followed for a shorter time. Verbal and nonverbal composite scores derived from intelligence quotient (IQ) tests showed less impairment at baseline than did other measures and were more likely to remain stable subsequently. Verbal memory and sustained attention were the most impaired at baseline, and verbal learning and flexibility in thinking showed the greatest tendency to decline over time. Cognitive functioning in survivors of high-grade glioma is best measured and monitored by tests that probe a broader spectrum of abilities than IQ. Neuropsychological measures used in this analysis lacked sensitivity at the lower end of the impaired range. Future studies should use tests better able to discern cognitive differences at low performance levels. Based on this experience, the authors conclude that most long-term survivors of high-grade glioma will have significant cognitive difficulties, usually evident by the first assessment; some patients will develop profound impairment years later, and few are capable of fully independent living.

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