Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat.

We have recently demonstrated that following a moderate contusion spinal cord injury (SCI) to rats, subsequent administration of basic fibroblast growth factor (bFGF) significantly enhances functional recovery and tissue sparing. To further characterize the effects of bFGF, we evaluated its efficacy after a more severe contusion injury at T(10) using the NYU impactor. Immediately after SCI, osmotic minipumps were implanted into the lateral ventricle and lumbar thecal sac to deliver bFGF at 3 or 6 microg per day versus control vehicle for 1 week. Animals were behaviorally tested for 6 weeks before histological assessment of tissue sparing through the injured segment and glial reactivity distal to the lesion. Compared to moderate SCI, all rats had more prolonged and sustained functional deficits 6 weeks after severe contusion. Subjects treated with bFGF had pronounced recovery of hindlimb movements from 2 to 6 weeks compared to controls, manifested in significantly higher behavioral scores. Only marginal tissue sparing was seen rostral to the injury in bFGF-treated spinal cords versus controls. Optical density measurements of astrocyte and microglial cell immunoreactivity in bFGF-treated spinal cords showed that after 6 weeks they approximated controls, although astrocyte immunoreactivity remained higher in controls rostrally. In summary, intrathecal infusion of bFGF following severe SCI significantly restores gross hindlimb motor function that is not correlated with significant tissue sparing. In light of previous evidence that pharmacological intervention with bFGF after moderate SCI enhances tissue preservation, the current findings indicate that yet undefined mechanisms contribute to the enhanced functional recovery following bFGF treatment.

Basic fibroblast growth factor (bFGF) enhances tissue sparing and functional recovery following moderate spinal cord injury.

The rapid increase in basic fibroblast growth factor (bFGF) production following spinal cord injury (SCI) in rats is thought to serve a role in the cellular processes responsible for the functional recovery often observed. In this study, bFGF was intrathecally administered continuously for 1 week beginning 30 min after a moderate (12.5 mm) spinal cord contusion in adult rats using the New York University impactor device. Osmotic minipumps were implanted into the lateral ventricle and lumbar thecal sac to deliver bFGF at a rate of 3 microg or 6 microg per day versus control vehicle. Animals were behaviorally tested for 6 weeks using the Basso, Beattie, Bresnahan locomotor rating scale and histologically assessed for both tissue sparing and glial reactivity rostral and caudal to the lesion. Rats treated with bFGF regained coordinated hindlimb movements earlier than controls and demonstrated consistent coordination from 4 to 6 weeks. Vehicle-treated rats showed only modest improvements in hindlimb function. The amount of spared tissue was significantly higher in bFGF-treated rats than in controls. Astrocyte and microglial reactivity was more pronounced in bFGF-treated animals versus controls. In summary, intrathecal infusion of exogenous bFGF following SCI significantly reduces tissue damage and enhances functional recovery. Early pharmacological intervention with bFGF following SCI may serve a neuroprotective role and/or create a proregenerative environment, possibly by modulating the neuroglial response.

The presence of 4-hydroxynonenal/protein complex as an indicator of oxidative stress after experimental spinal cord contusion in a rat model.

OBJECT: The authors tested the hypothesis that breach of the blood-spinal cord barrier (BSCB) will produce evidence of oxidative stress and that a similar staining pattern will be seen between 4-hydroxynonenal (HNE)/protein complexes and extravasated immunoglobulin G (IgG). METHODS: Adult female Fischer 344 rats, each weighing 200 to 225 g, were subjected to a spinal cord contusion at T-10 by means of a weight-drop device. Spinal cord tissue was assessed for oxidative stress by localizing extravasated plasma contents with a monoclonal antibody for rat IgG and protein conjugation with HNE, which is an aldehyde byproduct of lipid peroxidation. The animals were killed at 1 and 6 hours, and 1, 2, and 7 days after surgery. Maximum HNE/protein staining was observed at 2 days postinjury, and HNE/protein and IgG manifested similar staining patterns. Analysis revealed a graduated but asymmetrical rostral-caudal response relative to the T-10 injury site. Both HNE/protein complex and IgG staining revealed that the caudal levels T-11 and T-12 stained significantly more intensely than the rostral levels T-9 and T-8, respectively. A higher percentage of neurons positive for HNE/protein immunostaining was observed in spinal cord levels caudal to the injury site compared with equidistant rostral regions. Protein dot-blot assays also revealed a similar asymmetrical rostral-caudal HNE/protein content. To analyze the timing of the BSCB breach, another group of animals received identical contusions, and horseradish peroxidase (HRP) was injected 10 minutes before or at various times after injury (1, 3, and 6 hours, and 1, 2, and 7 days). Maximum HRP permeability was seen immediately after injury, with a significant decrease occurring by 1 hour and a return to control levels by 2 days posttrauma. CONCLUSIONS: Data from this study indicate possible compromise of neuronal, axonal, glial, and synaptic function after trauma, which may be a factor in motor deficits seen in animals after spinal cord contusion. The colocalization of the IgG stain with the HNE/protein stain is consistent with the hypothesis of a mutual cause-effect relationship between BSCB and oxidative stress in central nervous system trauma.

Alterations in temporal/spatial distribution of GFAP- and vimentin-positive astrocytes after spinal cord contusion with the New York University spinal cord injury device.

Astrocytes become reactive as a result of various types of lesions and upregulate 2 intermediate filaments, glial fibrillary acidic protein (GFAP), and the developmentally regulated protein vimentin. Young female Sprague-Dawley rats were subjected to a spinal cord contusion at segment T10 using the New York University injury device. Animals were killed at 1, 2, 7, 14, and 30 days postinjury. Horizontal spinal cord sections spanning segments T7-T13 were assessed with antibodies to both intermediate filament proteins. The number of gray matter GFAP-positive astrocytes increased by 2 days postinjury, with segments adjacent (proximal) to the injury site showing greater responses than areas several segments away (distal). By 30 days following injury, astroglial cell numbers returned to normal levels. Vimentin-positive astrocytes also showed a graded proximal/distal response by 2 days following injury. Proximal regions remained significantly higher at 30 days following injury than control animals. Rostral/caudal changes were also evident, with regions caudal to the injury showing significantly higher numbers of vimentin positive astrocytes than those rostral, indicating that gray matter areas caudal to spinal cord injury may undergo more stress following spinal cord injury.

Evaluation of the temporal evolution of acute spinal cord injury.

RATIONALE AND OBJECTIVES: After receiving a controlled injury to the thoracic cord, five rats were examined on a 1.5-T magnetic resonance (MR) imaging system at regular intervals over 1 month to assess evolution of the injury. METHODS: After the rats received pentobarbital anesthesia, a T10 laminectomy was performed on them, which exposed the dura over the dorsal surface of the spinal cord. With the animal placed in a New York University weight-drop device, a 10-g rod with a flat brass tip was dropped (free-fall) from a height of 50 mm to impact the cord. After injury, the incision was closed with suture material. Each animal was imaged on the day of injury, and at 7, 14, and 28 days after injury. Before contrast injection was administered, sagittal sections were obtained with T2 fast-spin echo and T1-spin echo technique. Each rat then received 0.3-mmol/kg gadoteridol (Gd HP-DO3A or ProHance) intravenously, with the T1 scan repeated. At 28 days, the animals were killed, and the cord was fixed and embedded in paraffin for histologic evaluation. RESULTS: The intensity of cord enhancement in the region of injury, after intravenous (i.v.) contrast injection, was at a maximum on the day of injury, and it decreased in a steady fashion thereafter. The intensity was 11.7 +/- 0.6 on the day of injury, 9.7 +/- 2.6 on day 7, 6.3 +/- 5.3 on day 14, and 0.0 +/- 2.3 on day 28. The results on day 0 and 7 were statistically significant in terms of a difference from that on day 28, with a P value < 0.001. The length of cord injury, assessed postcontrast, also decreased in a steady fashion from the day of injury. The length of injury (in cm) was 1.1 +/- 0.1 on the day of injury, 0.5 +/- 0.2 on day 7, 0.3 +/- 0.1 on day 14, and 0.1 +/- 0.1 on day 28. The results on day 0 and 14 were statistically significant in terms of a difference from those at the next time point, with P values from < 0.01 to < 0.001. Visually, on T2 images, substantial edema was noted on day 0, with progression to focal cord atrophy and gliosis by day 28. CONCLUSIONS: Acute spinal cord injury in a rat model is well visualized on pre- and postcontrast MR scans at 1.5 T. Observation of T2 changes and disruption of the blood-spinal cord barrier provide markers for temporal assessment of spinal cord injury in the rat model.

Cervical paraganglioma with subsequent intracranial and intraspinal metastases. Case report.

Paragangliomas, tumors derived from the extra-adrenal paraganglion system, have commonly been found in the retroperitoneum, abdomen, mediastinum, skull base, and neck. Rare intraspinal cases have included involvement of the cauda equina and filum terminale, and a recent case has been reported of thoracic cord paraganglioma with metastasis to the cauda equina. The authors present the case of a patient with a cervical paraganglioma who underwent subtotal resection followed by postoperative irradiation; she subsequently developed multiple intracranial and intraspinal metastases 7 months following the first decompression procedure.