Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor

2002 ◽  
Vol 97 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Francesco Facchiano ◽  
Eduardo Fernandez ◽  
Salvatore Mancarella ◽  
Giulio Maira ◽  
Massimo Miscusi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Growth Factors ◽  
Corticospinal Tract ◽  
Vascular Endothelial ◽  
Adult Rats ◽  
Content Type ◽  
Injured Area ◽  
Cord Injury ◽  
Endothelial Growth Factor ◽  
Fine Print

Object. After spinal cord transection in adult rats, the axons of the corticospinal tract (CST) degenerate retrogradely and do not regenerate. This phenomenon is thought to be related to either secondary ischemia or deficiency of growth factors. To overcome the deficiency of both blood flow and growth factors, the authors added exogenous vascular endothelial growth factor (VEGF165) to the transected spinal cord either as recombinant protein alone or combined with an adenovirus coding for VEGF165. Because most growth factors are rapidly inactivated in the extracellular environment, the authors used an adenovirus coding for VEGF165 to maintain its activity for several days. Methods. In adult rats, the dorsal two thirds of the spinal cord were transected at the T-8 level. In experimental rats, either human recombinant VEGF165 or a combination of this factor and a replication-defective adenovirus coding for VEGF165 (Ad.CMV.VEGF165) was applied at the lesion site. Both recombinant VEGF165 alone and combined with Ad.CMV.VEGF165 were mixed with Matrigel, which is a reconstituted membrane basement protein extract. Control rats received Matrigel alone or Matrigel plus an adenoviral vector containing the LACZ gene (Ad.CMV.LACZ). Thirty days after spinal cord injury, the number of newly formed blood vessels was assessed in the injured area. In addition, the sensorimotor cortex was injected with anterogradely transported horseradish peroxidase (HRP) to label the CST axons in the spinal cord and to evaluate the extent of retrograde axonal degeneration and regeneration. Gene transfer was assessed using semiquantitative reverse transcription—polymerase chain reaction analysis, enzyme-linked immunosorbent assay for human VEGF and β-galactosidase expression in injured rats treated with Matrigel plus Ad.CMV.LACZ, Matrigel plus Ad.CMV.VEGF165, and untreated injured rats. A strong gene transfer in the spinal cord tissue of adenovirus-treated rats was found from Day 3 to Day 10 postinjury, confirming infection. In the injured spinal cord area, a significant increase of blood vessels (300% over control, p < 0.005) occurred both in rats treated with recombinant VEGF165 alone and in those treated with the combination of recombinant VEGF165 and Ad.CMV.VEGF165. Also, in both of these groups of animals the retrograde degeneration of CST axons was significantly reduced compared with rats treated with Matrigel alone or Matrigel plus Ad.CMV.LACZ. Furthermore, in rats treated with recombinant VEGF165 alone or combined with Ad.CMV.VEGF165, a few HRP-labeled CST axons, which were not detectable in control rats, were seen distal to the spinal cord injury, indicating some regeneration across the injured area. Conclusions. These results indicate that locally applied VEGF exerts angiogenic as well as neurotrophic effects in the injured spinal cord of rats.

Vascular endothelial growth/permeability factor in spinal cord injury

1999 ◽  
Vol 90 (2) ◽  
pp. 220-223 ◽  
Author(s):  
Jesús Vaquero ◽  
Mercedes Zurita ◽  
Santiago de Oya ◽  
Santiago Coca
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Traumatic Injury ◽  
Vascular Endothelial ◽  
Content Type ◽  
Permeability Factor ◽  
Tissue Edema ◽  
Cord Injury ◽  
Cell Expression ◽  
Fine Print

Object. Predicated on the hypothesis that this cytokine can contribute to the development of vascular hyperpermeability, leading to tissue edema after trauma, the purpose of this study was to determine the presence in tissue of vascular endothelial growth/permeability factor (VEG/PF) after experimental spinal cord injury. Methods. The presence of VEG/PF was studied at 8 hours and 2, 8, and 14 days after a traumatic injury in adult Wistar rats. Studies were conducted in which a monoclonal antibody to the VEG/PF was used. Strong VEG/PF immunoreactivity was detected in the walls of pial and intramedullary vessels and in reactive astrocytes 8 hours posttrauma and was unchanged on Days 2 and 8. By Day 14, immunoreactivity decreased, and most of the arterioles from the pia and gray matter showed no mural VEG/PF. Conclusions. The authors' present findings suggest a role for this cytokine in the development of tissue edema after spinal cord trauma and point to the possible usefulness of a therapeutic approach to spinal cord injury based on blocking the cell expression of VEG/PF or its physiological effects.

scholarly journals Rat Hippocampal Neural Stem Cell Modulation Using PDGF, VEGF, PDGF/VEGF, and BDNF

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Neus Gomila Pelegri ◽  
Catherine A. Gorrie ◽  
Jerran Santos
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factors ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Platelet Derived Growth Factor ◽  
Vascular Endothelial ◽  
Cord Injury ◽  
Endothelial Growth Factor

Neural stem cells have become the focus of many studies as they have the potential to differentiate into all three neural lineages. This may be utilised to develop new and novel ways to treat neurological conditions such as spinal cord and brain injuries, especially if the stem cells can be modulated in vivo without additional invasive surgical procedures. This research is aimed at investigating the effects of the growth factors vascular endothelial growth factor, platelet-derived growth factor, brain-derived neurotrophic factor, and vascular endothelial growth factor/platelet-derived growth factor on hippocampal-derived neural stem cells. Cell growth and differentiation were assessed using immunohistochemistry and glutaminase enzyme assay. Cells were cultured for 14 days and treated with different growth factors at two different concentrations 20 ng/mL and 100 ng/mL. At 2 weeks, cells were fixed, and immunohistochemistry was conducted to determine cellular differentiation using antibodies against GFAP, nestin, OSP, and NF200. The cell medium supernatant was also collected during treatment to determine glutaminase levels secreted by the cells as an indicator of neural differentiation. VEGF/PDGF at 100 ng/mL had the greatest influence on cellular proliferation of HNSC, which also stained positively for nestin, OSP, and NF200. In comparison, HNSC in other treatments had poorer cell health and adhesion. HNSC in all treatment groups displayed some differentiation markers and morphology, but this is most significant in the 100 ng/ml VEGF/PDGF treatment. VEGF/PDGF combination produced the optimal effect on the HNSCs inducing the differentiation pathway exhibiting oligodendrocytic and neuronal markers. This is a promising finding that should be further investigated in the brain and spinal cord injury.

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.

Therapeutic trial of hypercarbia and hypocarbia in acute experimental spinal cord injury

1984 ◽  
Vol 61 (5) ◽  
pp. 925-930 ◽  
Author(s):  
Ronald W. J. Ford ◽  
David N. Malm
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Mortality Rates ◽  
Therapeutic Trial ◽  
Tissue Preservation ◽  
Content Type ◽  
Experimental Spinal Cord Injury ◽  
Cord Injury ◽  
Fine Print

✓ Hypocarbia, normocarbia, or hypercarbia was maintained for an 8-hour period beginning 30 minutes after acute threshold spinal cord injuries in cats. No statistically significant differences in neurological recovery or histologically assessed tissue preservation were found among the three groups of animals 6 weeks after injury. No animal recovered the ability to walk. It is concluded that maintenance of hypercarbia or hypocarbia during the early postinjury period is no more therapeutic than maintenance of normocarbia. Mortality rates and tissue preservation data suggest, however, that postinjury hypocarbia may be less damaging than hypercarbia.

Ultrastructural scoring of graded acute spinal cord injury in the rat

2002 ◽  
Vol 97 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Selcuk Palaoglu ◽  
H. Selcuk Surucu ◽  
Mutlu Hayran ◽  
Etem Beskonakli
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Behavioral Assessment ◽  
Traumatic Injury ◽  
Significant Negative Correlation ◽  
Content Type ◽  
Cord Injury ◽  
Contusion Injury ◽  
Weight Drop ◽  
Fine Print

Object. There is a need for an accurate quantitative histological technique that also provides information on neurons, axons, vascular endothelium, and subcellular organelles after spinal cord injury (SCI). In this paper the authors describe an objective, quantifiable technique for determining the severity of SCI. The usefulness of ultrastructural scoring of acute SCI was assessed in a rat model of contusion injury. Methods. Spinal cords underwent acute contusion injury by using varying weights to produce graded SCI. Adult Wistar rats were divided into five groups. In the first group control animals underwent laminectomy only, after which nontraumatized spinal cord samples were obtained 8 hours postsurgery. The weight-drop technique was used to produce 10-, 25-, 50-, and 100-g/cm injuries. Spinal cord samples were also obtained in the different trauma groups 8 hours after injury. Behavioral assessment and ultrastructural evaluation were performed in all groups. When the intensity of the traumatic injury was increased, behavioral responses showed a decreasing trend. A similar significant negative correlation was observed between trauma-related intensity and ultrastructural scores. Conclusions. In the present study the authors characterize quantitative ultrastructural scoring of SCI in the acute, early postinjury period. Analysis of these results suggests that this method is useful in evaluating the degree of trauma and the effectiveness of pharmacotherapy in neuroprotection studies.

The therapeutic window for spinal cord decompression in a rat spinal cord injury model

2005 ◽  
Vol 3 (4) ◽  
pp. 302-307 ◽  
Author(s):  
Christopher B. Shields ◽  
Y. Ping Zhang ◽  
Lisa B. E. Shields ◽  
Yingchun Han ◽  
Darlene A. Burke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Stenosis ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Therapeutic Window ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Fine Print

Object. There are no clinically based guidelines to direct the spine surgeon as to the proper timing to undertake decompression after spinal cord injury (SCI) in patients with concomitant stenosis-induced cord compression. The following three factors affect the prognosis: 1) severity of SCI; 2) degree of extrinsic spinal cord compression; and 3) duration of spinal cord compression. Methods. To elucidate further the relationship between varying degrees of spinal stenosis and a mild contusion-induced SCI (6.25 g-cm), a rat SCI/stenosis model was developed in which 1.13- and 1.24-mm-thick spacers were placed at T-10 to create 38 and 43% spinal stenosis, respectively. Spinal cord damage was observed after the stenosis—SCI that was directly proportional to the duration of spinal cord compression. The therapeutic window prior to decompression was 6 and 12 hours in the 43 and 38% stenosis—SCI lesions, respectively, to maintain locomotor activity. A significant difference in total lesion volume was observed between the 2-hour and the delayed time(s) to decompression (38% stenosis—SCI, 12 and 24 hours, p < 0.05; 43% stenosis—SCI, 24 hours, p < 0.05) indicating a more favorable neurological outcome when earlier decompression is undertaken. This finding was further supported by the animal's ability to support weight when decompression was performed by 6 or 12 hours compared with 24 hours after SCI. Conclusions. Analysis of the findings in this study suggests that early decompression in the rat improves locomotor function. Prolongation of the time to decompression may result in irreversible damage that prevents locomotor recovery.

Cruciate paralysis

1986 ◽  
Vol 65 (1) ◽  
pp. 108-110 ◽  
Author(s):  
Daniel Dumitru ◽  
James E. Lang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rare Case ◽  
Motor Vehicle ◽  
Motor Vehicle Accident ◽  
Cervical Spinal Cord ◽  
Content Type ◽  
Vehicle Accident ◽  
Cord Injury ◽  
Fine Print

✓ A rare case of cruciate paralysis is reported in a 39-year-old man following a motor-vehicle accident. The differentiation of this syndrome from a central cervical spinal cord injury is delineated.

Bladder function after incomplete spinal cord injury in mice: quantifiable outcomes associated with bladder function and efficiency of dehydroepiandrosterone as a therapeutic adjunct

2004 ◽  
Vol 100 (1) ◽  
pp. 56-61
Author(s):  
Pierre-Yves Mure ◽  
Mark Galdo ◽  
Nathalie Compagnone
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mouse Model ◽  
Collagen Type ◽  
Neurological Recovery ◽  
Bladder Function ◽  
Type I ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

Object. The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. Methods. A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. Conclusions. The authors found that early recovery of controlled voiding is predictive of motor recovery.

Immediate effects of spinal cord stimulation in spinal spasticity

1985 ◽  
Vol 62 (4) ◽  
pp. 558-562 ◽  
Author(s):  
Giancarlo Barolat-Romana ◽  
Joel B. Myklebust ◽  
David C. Hemmy ◽  
Barbara Myklebust ◽  
William Wenninger
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Stimulation ◽  
Content Type ◽  
Clinical Observations ◽  
Cord Injury ◽  
Epidural Spinal Cord Stimulation ◽  
Stimulation System ◽  
Fine Print

✓ Six patients with intractable spasms after spinal cord injury underwent implantation of an epidural spinal cord stimulation system. All the patients experienced good relief postoperatively. In three patients spinal cord stimulation consistently produced immediate inhibition of the spasms. This was evident within less than 1 minute of stimulation. Conversely, the spasms reappeared within less than 1 minute after cessation of the stimulation. The clinical observations were confirmed by polygraphic electromyographic recordings.

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