ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

THE FAILURE OF the adult mammalian central nervous system (CNS) to regenerate after injury has long been viewed as a unique phenomenon resulting from the specific nature of this system. The finding that some CNS axons could be induced to regrow if provided with a permissive environment suggested that this failure is a result, at least in part, of the nature of the postinjury neuronal environment. It was further shown that the involvement of inflammatory cells, particularly macrophages, in postinjury processes in the CNS is limited. We have suggested that, to achieve recovery after injury, the adult mammalian CNS may require the assistance of the same postinjury factors as those involved in the recovery of spontaneously regenerating systems but that its accessibility to such assistance is restricted. Accordingly, we proposed that it might be possible to circumvent the restriction, allowing regeneration to occur. We showed that the implantation of autologous macrophages, which had been prestimulated by exposure to a regenerative (sciatic) nerve, into completely transected spinal cords of adult rats led to partial motor recovery. This treatment intervenes in the postinjury process by simulating in the axotomized CNS the events that occur naturally in spontaneously regenerating systems.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:This laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion to the upper thoracic region.METHODS:The accumulation of LCMs in the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, 3,3′-dioctadecyloxacarbocyanine perchlorate. Indices of glial fibrillary acidic protein were measured concomitantly with 3,3′-dioctadecyloxacarbocyanine perchlorate-labeled LCMs using confocal microscopy.RESULTS:There was no aggregation of LCMs accumulated 1 and 6 hours after injury; however, when given 2, 4, and 7 days after injury, LCMs showed a clear affinity for the injured region. LCM aggregation shifted from the central necrotic area of the injury Day 2 and postinjury Day 4 to the white matter among glial fibrillary acidic protein-positive astrocytes by postinjury Day 7.CONCLUSION:Affinity of LCMs for spinal cord injury sites may be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by glial fibrillary acidic protein-positive astrocytes in adjacent white matter. These findings suggest a potential for using LCMs as a delivery vehicle to concentrate lipid-soluble agents in spinal cord injury sites.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:Elevated intracranial pressure (ICP) is related to mortality after intracerebral hemorrhage (ICH). To develop effective strategies for the medical treatment of ICP in cases of ICH, we evaluated the therapeutic efficacy of mannitol and hypertonic saline in a canine model of ICH.METHODS:We introduced ICH in three groups of anesthetized mongrel dogs, consisting of seven animals each, by autologous blood injection (5.5-7.5 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. We evaluated the effect of iso-osmolar doses (5.5 mOsm/kg) of intravenously administered mannitol (1 gm/kg), 3% NaCl (5.3 ml/kg), or 23.4% NaCl (0.7 ml/kg) administered 2 hours after the introduction of hematoma, on the following: ICP, cerebral perfusion pressure, cerebral oxygen extraction and oxygen consumption, and regional cerebral blood flow in regions around and distant to the hematoma. All measurements were recorded at baseline, before treatment, and 15, 30, 60, and 120 minutes after treatment. We also evaluated the water content (wet/dry weight) and blood-brain barrier permeability (Evans blue method) in pathologically demarcated regions of brain.RESULTS:There was an immediate reduction in ICP (mm Hg ± standard error of the mean) in the 23.4% NaCl (27.6 ± 4 to 11.0 ± 2 mm Hg,P= 0.001), 3% NaCl (23.7 ± 3 to 14.7 ± 2 mm Hg,P= 0.009), and mannitol (25.6 ± 3 to 15.9 ± 4 mm Hg,P= 0.02) groups. Compared with pretreatment values, ICP was significantly lower in both the 23.4% NaCl (12.3 ± 2 mm Hg,P= 0.002) and 3% NaCl (17.6 ± 2 mm Hg,P= 0.008) groups but not in the mannitol group (18.7 ± 4 mm Hg,P= 0.08) 15 minutes after the administration of treatment. There was a gradual rise in ICP observed in the 23.4% NaCl and mannitol groups with time. Only in the 3% NaCl group was the ICP significantly lower than the pretreatment value at 120 minutes (18.0 ± 2 mm Hg,P= 0.02). A significantly higher cerebral perfusion pressure (108.4 ± 4 versus 79.6 ± 10 mm Hg,P= 0.048) and lower water content in the lesioned white matter (65.5 ± 1% versus 67.9 ± 1%,P= 0.07) was observed 2 hours after treatment in animals receiving 3% NaCl compared with animals receiving mannitol. There were no significant differences observed in regional cerebral blood flow, oxygen extraction, or oxygen consumption at any time point among the three groups.CONCLUSION:Hypertonic saline, in both 3 and 23.4% concentrations, is as effective as mannitol in the treatment of intracranial hypertension observed in association with ICH. Hypertonic saline may have a longer duration of action, particularly when used in 3% solution. None of three treatment regimens influence regional cerebral blood flow or cerebral metabolism.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

OBJECTIVE:The source of fluid and the mechanism of cyst enlargement in syringomyelia are unknown. It has been demonstrated that cerebrospinal fluid (CSF) normally flows from the subarachnoid space through perivascular spaces and into the spinal cord central canal. The aim of this study was to investigate whether this flow continues during cyst formation in an animal model of syringomyelia and to determine the role of subarachnoid CSF flow in this model.METHODS:The intraparenchymal kaolin model of noncommunicating syringomyelia was established in 78 Sprague-Dawley rats. Horseradish peroxidase was used as a tracer to study CSF flow at 1 day, 3 days, 1 week, and 6 weeks after kaolin injection. CSF flow was studied at 0, 10, and 30 minutes after horseradish peroxidase injection into the cisterna magna or thoracic subarachnoid space.RESULTS:The central canal became occluded at the level of the kaolin injection and at one or more rostral levels. Segments of the central canal isolated between occlusions gradually dilated, and axonal retraction balls were detected in the surrounding white matter. There was a partial blockage of subarachnoid CSF flow at the site of the kaolin injection, both in a rostral-caudal direction and in a caudal-rostral direction. Horseradish peroxidase was detected at all time points, in a distinctive pattern, in perivascular spaces and the central canal. This pattern was seen even where segments of the central canal were isolated and dilated.CONCLUSION:In this animal model, noncommunicating syringes continue to enlarge even when there is evidence that they are under high pressure. There may be an increase in pulse pressure rostral to the block of subarachnoid CSF flow, causing an increase in perivascular flow and contributing to syrinx formation. The source of fluid in noncommunicating syringomyelia may be arterial pulsation-dependent CSF flow from perivascular spaces into the central canal.

ISSN:0148-396X    

出版商:OVID    

年代:1999

数据来源: OVID