摘要:

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

In an attempt to improve and expedite the care of head-injured children, data have been published recommending burr hole exploration in lieu of computed tomography for children with signs of brain stem compression or with a Glasgow Coma Scale score of 3. Exploratory burr holes revealed a high incidence of subdural hematomas, and removal of the hematomas improved survival. We are reporting 19 consecutive children with Glasgow Coma Scale scores of 3. Coma score evaluation was confounded by intubation, sedation, pharmacological paralysis, and posttraumatic seizures. We found no radiographical or postmortem pathological evidence of intracranial hemorrhage, which would warrant operative intervention. A high incidence of multisystem injuries and high cervical spine injuries would have made early intervention both dangerous and inappropriate. Although there is a definite role for emergency trephination, routine exploratory burr holes for children with a Coma score of 3 is not justified.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The cerebellomedullary fissure, the only entrance or exit to the fourth ventricle, is surrounded rostrally by the cerebellar tonsils and the biventral lobules and caudally by the medulla oblongata, the tela choroidea, and the lateral recesses. This fissure is an important route in operations on the fourth ventricle. We studied the microsurgical and magnetic resonance imaging (MRI) anatomy of the fissure by using autopsied normal cerebellum. MRI revealed that the fissure is visible as a slit and is indicated by the enhanced choroid plexus and the flocculus. Oriented by the anatomical information thus obtained, we have surgically treated nine patients with a tumor either in or around the fourth ventricle. Preoperative MRI clearly demonstrated the tumors in relation to the cerebellomedullary fissure. It revealed the precise anatomical location and extension of the tumor, not only its inferior extension but also its lateral one. The MRI findings and microsurgical anatomy of the cerebellomedullary fissure were quite useful for the removal of the tumors in the fourth ventricle.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The influence of vasospasm on the permeability of the major cerebral arteries was studied using horseradish peroxidase (HRP). Experimental vasospasm was produced in canine basilar arteries by successive injections, 2 days apart, of autologous blood into the cisterna magna. HRP was injected intravenously or intracisternally 48 hours after the second injection of autologous blood, and all animals were killed by perfusion fixation 60 minutes after the injection of HRP. The distribution of HRP was observed by transmission electron microscopy. In 10 dogs injected intracisternally with HRP, 5 control dogs demonstrated a moderate amount of HRP in the intermuscular space through the adventitia. Five dogs with subarachnoid hemorrhages (SAHs) showed a moderate amount of HRP in the intermuscular space. In 11 dogs injected intravenously with HRP, 5 control dogs showed no leakage of HRP into vessel walls. Six dogs with SAHs showed HRP in the interendothelial space. These findings suggest that, despite SAHs, HRP seems to be able to circulate in the cerebrospinal fluid and makes contact with the cerebral vessels. This study suggests the possibility that spasmogenic substances may penetrate the vessel wall from the extraluminal side more easily than from the intraluminal side.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Cell culture lines from human cerebral arteries showing vasospasm after subarachnoid hemorrhage were established from three autopsy cases. Each culture line showed the ultrastructural characteristics of myofibroblasts. Decreased α-actin antigenicity, demonstrated using the anti-smooth muscle cell α-actin antibody, was observed in cultured cells possessing abundant F-actin. When incorporated into the three-dimensional collagen matrix in vitro, the cultured cells compacted the collagen lattice at a rate equivalent to that of human dermal fibroblasts. Lattice compaction was significantly accelerated by cerebrospinal fluid taken from patients with symptomatic vasospasm. Compaction was completely inhibited by the addition of 10−6mol/L verapamil or 100 U/mL heparin. Neither nimodipine (10−5mol/L) nor nicardipine (10−5mol/L) inhibited compaction, and endothelin (10−6mol/L) and potassium chloride (40 mmol/L) had no effect. The morphological change of cells in the collagen lattice suggests that both verapamil and heparin affect cellular motility, filopodial protrusion, and cell attachment. These data suggest that myofibroblasts in human cerebral arteries differ from medial smooth muscle cells and can generate a force rearranging the proliferated collagen matrix present after subarachnoid hemorrhage. This reorganization can contribute to, or be responsible for, sustained vasoconstriction. Consequently, current treatment for vasospasm may need to be reevaluated to include the nonmuscle components in the vessel wall.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A culture of smooth muscle cells obtained from monkey middle cerebral arteries was developed to allow quantitative assessment of intracellular calcium and immunofluorescence analysis after various periods of exposure to oxyhemoglobin. Intracellular calcium concentration was examined for up to 7 days after a single exposure to oxyhemoglobin. Intracellular calcium concentrations were measured with the fluorescent dye fura-2 and were significantly elevated for 7 days after exposure to oxyhemoglobin (P< 0.01). Less than 2 minutes after application of oxyhemoglobin, there was marked elevation of intracellular calcium from the control value of 75 ± 2 nmol/L to 240 ± 28 nmol/L (P< 0.01 by analysis of variance). Intracellular calcium concentration of cells exposed for 24 hours to oxyhemoglobin and then grown in normal oxyhemoglobin-free medium fell close to normal levels on Days 3 and 7. On Day 3, the increase in intracellular calcium that followed repeated daily exposure to oxyhemoglobin was greater than that resulting from a single application of oxyhemoglobin (P< 0.01 by Student'sttest), but by Day 7 the elevation produced by these different approaches was similar. Smooth muscle cells exposed to oxyhemoglobin showed a reduction in immunoreactivity to α-actin. These data support the hypothesis that disruption of intracellular calcium regulation and calcium overloading may be important in the process of cell injury, which results in vasoconstriction and sometimes cell death, after exposure to oxyhemoglobin.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effect of the synthetic multiserine protease inhibitor FUT-175 on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. The SAH in rabbits was simulated by a single injection of autologous arterial blood into the cisterna magna, and, for 7 days, the caliber of each basilar artery was examined several times via angiogram. In 10 SAH rabbits, the peak of the arterial narrowing was observed on Day 2. In this model, the effect of intravenous administrations of FUT-175 was examined. Twenty-seven SAH rabbits were randomly divided into three groups, and 3 doses of 1, 2, or 3 mg of FUT-175 were administered intravenously. Angiographic arterial narrowing on Day 2 in nontreated SAH rabbits (Control) was 35% compared with 21, 5, and 14% in rabbits treated with a total of 3 (Group A; n = 9), 6 (Group B; n = 13), and 9 mg (Group C; n = 5) of FUT-175, respectively. There were statistically significant differences in the arterial calibers between Group A and the Control on Days 1 and 2, between Group B and the Control from days 1 to 4, and between Group C and the Control from days 1 to 4. In three other rabbits, after vasospasm reached its maximum on Day 2, no vasodilatory effect was observed when a total of 6 mg of FUT-175 was administered intravenously. The results indicate that the inhibition of the plasma serine protease cascades at an early stage of SAH prevents the development of cerebral vasospasm. The possibility that the delayed pathological arterial narrowing is a result of the inflammation caused by the activation of plasma protease cascades at an early stage of SAH is discussed.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The therapeutic effect of the synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. Twenty-three patients with severe SAH who were admitted between February and July 1990 and who underwent surgery within 48 hours of the initial aneurysmal rupture were treated with an intravenous administration of FUT-175 soon after the operation. The patients were divided randomly into three groups, each receiving a different dose of FUT-175 (Group A, 20 mg every 12 hours for 4 days; Group B, 20 mg every 6 hours for 4 days, Group C, 40 mg every 6 hours for 4 days). The results were compared with another group of twenty-two patients with severe SAH who were admitted before February 1990 and received equivalent treatment, except they were not treated with FUT-175. In 64% of all the patients treated with FUT-175 (Groups A, B, C), and in 85% of those treated with higher doses of FUT-175 (Groups B and C), there was no spasm or only mild vasospasm on the angiogram. The incidence of a delayed ischemic neurological deficit significantly decreased from 55% in the control group to 13% in all patients treated with FUT-175 and to 7% in the patients treated with higher doses (P< 0.05). The incidence of cerebral infarction resulting from vasospasm significantly decreased from 43% in the control group to 9% in patients treated with FUT-175. In the patients treated with higher doses of FUT-175 (Groups B and C), none developed cerebral infarction. The outcome 1 month after SAH also significantly improved in patients treated with FUT-175. The patients with a good outcome accounted for 67% of the patients treated with FUT-175, as compared with 35% in the control group. The patients with a poor outcome accounted for only 9% of patients treated with FUT-175, as compared with 36% in the control group. These figures were much more satisfactory in the patients treated with higher doses of FUT-175, i.e., 71% of the patients had a good outcome and none had a poor outcome. FUT-175 is a promising drug for preventing cerebral vasospasm and delayed ischemic neurological deficit after SAH. Additional controlled studies with larger numbers of patients are necessary.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

It is well known that after reconstruction of sectioned peripheral nerves in adult mammals, denervated muscles are reinnervated by the axotomized motoneurons lying in the original motonucleus. It is less well known that these muscles can also be reinnervated by uninjured motoneurons lying in the homologous contralateral motonucleus. Therefore, after nerve reconstruction, bilateral motoneuron reinnervation of muscles can occur. Contralateral motoneurons sprout axons that cross the midline, grow in the reconstructed nerve, and reach muscle targets. This phenomenon was observed after reconstruction of several different peripheral nerves in adult mammals, including the oculomotor nerve in guinea pigs and the facial and sciatic nerves in rats. The retrograde axonal transport of horseradish peroxidase was used for the study of the organization of the brainstem and spinal cord motonuclei. Horseradish peroxidase was injected into the medial rectus muscle, the stylohyoid muscle, and the trunk of the sciatic nerve. The distance between the homologous motonuclei of both sides influenced the occurrence of this phenomenon. In fact, bilateral reinnervation of muscles after nerve reconstruction was found in 36% (sciatic nerve), 50% (facial nerve), and 100% (oculomotor nerve) of the operated animals. The total number of contralateral motoneurons found were 14% (oculomotor nerve), 8% (facial nerve), and 5% (sciatic nerve). Bilateral reinnervation of muscles was evoked by both immediate and delayed peripheral nerve repair and was a stable phenomenon, seen between 3 and 21 months after facial nerve reconstruction.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To elucidate the pathophysiology of mental disturbances associated with chronic subdural hematoma, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced computed tomographic scans in 12 patients who had chronic subdural hematomas and manifested mental disturbances. In 2 patients who had no headache or hemiparesis, minimal mass effect, and severe multiple infarctions on computed tomographic scan, mentation did not improve after surgery. The CBF reduction was severe, and it further deteriorated after surgery. On the other hand, mentation improved to a varied extent in the other 10 patients, who had headache and/or hemiparesis and minimal, moderate, or severe mass effect and minimal or moderate multiple infarctions on computed tomographic scan. The CBF reduction was diffuse on both sides, but was more marked in the thalamus and putamen than it was in the cortex and subcortex. It was restored after surgery, but insufficiently. The restoration rate was statistically significant only in the thalamus, on both sides (with and without hematoma) (P< 0.05). Dementia scores and CBF values after surgery were correlated on the side with the hematoma in the frontal cortex and thalamus (P< 0.01) and in the hemisphere and temporoparietal cortex (P< 0.05). There was no correlation on the side with the hematoma in the occipital cortex, putamen, and frontal and temporoparieto-occipital subcortices or on the side without the hematoma. The thalamus undergoes displacement and distortion by the hematoma, which in turn leads to changes in consciousness. Postoperative residual mental deficits consist primarily of dementia related to preexisting multiple infarctions. Surgical benefits tend to be limited to disturbance of consciousness and not to other categories of mental function.

ISSN:0148-396X    

出版商:OVID    

年代:1992

数据来源: OVID