Studies on embryonic transplants to the transected spinal cord of adult rats

1989 ◽  
Vol 70 (3) ◽  
pp. 454-462 ◽  
Author(s):  
Roberto Pallini ◽  
Eduardo Fernandez ◽  
Carlo Gangitano ◽  
Aurora Del Fà ◽  
Corrado Olivieri-Sangiacomo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Tissue ◽  
Adult Rats ◽  
Thin Sections ◽  
Content Type ◽  
Retrograde Degeneration ◽  
Limited Degree ◽  
Transplantation Site ◽  
Fine Print ◽  
Inclined Plane Test

✓ Spinal cord tissue was obtained from 13- and 14-day embryonic rats and homologously grafted to the completely transected spinal cord of adult rats. Eight and 12 weeks after grafting, clinical, electrophysiological, histological, and neuroanatomical studies were performed. Motor performance of the hosts was assessed by the inclined-plane test. The conduction of nerve impulses across the lesion-transplantation site was evaluated by recording the spinal corticomotor and somatosensory evoked potentials. The survival, growth, differentiation, and parenchymal integration of the graft were documented histologically on semi-thin sections. The axonal interactions between the host spinal cord and the graft as well as the posttraumatic retrograde degeneration of corticospinal axons were investigated using the horseradish peroxidase (HRP) technique. Clinical and electrophysiological assessments did not demonstrate any functional activity of the graft. On histological examination, grafted neurons showed a survival rate of 55%. Such neurons exhibited a limited degree of growth and differentiation. The extent of parenchymal integration between the host spinal cord and the graft varied considerably among different specimens and in the various regions of every specimen. The HRP investigations demonstrated that some axonal interactions between the host spinal cord and the graft had occurred. Regenerated axons arising from both the spinal cord and the dorsal root ganglia of the host entered the graft and elongated in it. Also, axons from the grafted neurons were able to grow for some distance in the host spinal cord. The phenomenon of the posttraumatic retrograde degeneration of corticospinal axons was not affected by this embryonic tissue grafting.

Effect of anti—rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes

2001 ◽  
Vol 95 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Metin Tuna ◽  
Sait Polat ◽  
Tahsin Erman ◽  
Faruk Ildan ◽  
A. Iskender Göçer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Tissue ◽  
Inos Activity ◽  
Content Type ◽  
Cord Injury ◽  
Oxide Synthase ◽  
Fine Print ◽  
Inducible Nitric Oxide

Object. The inflammatory cells that accumulate at the damaged site after spinal cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce the expression of inducible nitric oxide synthase (iNOS). Any increased production of NO by iNOS activity would aggravate the primary neurological damage in SCI. If this mechanism does occur, the direct or indirect effects of IL-6 antagonists on iNOS activity should modulate this secondary injury. In this study, the authors produced spinal cord damage in rats and applied anti—rat IL-6 antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the spinal cord tissue activities of Na+-K+/Mg++ adenosine-5′-triphosphatase (ATPase) and superoxide dismutase, evaluated iNOS immunoreactivity, and examined ultrastructural findings to assess the results of this treatment. Methods. Seventy rats were randomly allocated to four groups. Group I (10 rats) were killed to provide normal spinal cord tissue for testing. In Group II 20 rats underwent six-level laminectomy for the effects of total laminectomy alone to be determined. In Group III 20 rats underwent six-level T2–7 laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in the 20 Group IV rats, but these rats also received one (2 µg) intraperitoneal injection of anti—rat IL-6 antibody immediately after the injury and a second dose 24 hours posttrauma. Half of the rats from each of Groups II through IV were killed at 2 hours and the other half at 48 hours posttrauma. The exposed cord segments were immediately removed and processed for analysis. Conclusions. The results showed that neutralizing IL-6 bioactivity with anti—rat IL-6 antibody significantly attenuates iNOS activity and reduces secondary structural changes in damaged rat spinal cord tissue.

Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury

2001 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Isabel Zurita
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Content Type ◽  
Cord Injury ◽  
Positive Immunostaining ◽  
Fine Print

Object. A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI. Methods. The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord. Conclusions. These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.

Norepinephrine levels in experimental spinal cord trauma

1977 ◽  
Vol 46 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Stephen E. Rawe ◽  
Robert H. Roth ◽  
Margaret Boadle-Biber ◽  
William F. Collins
Keyword(s):  
Spinal Cord ◽  
Tyrosine Hydroxylase ◽  
Concentration Gradient ◽  
Neurological Function ◽  
Spinal Cord Tissue ◽  
Spinal Cord Trauma ◽  
Content Type ◽  
Spinal Cord Segment ◽  
Fine Print

✓ Levels of norepinephrine (NE) in the spinal cord tissue of nontraumatized cats are highest in the cervical and lumbar enlargements. A rather uniform but slightly increasing concentration gradient from cephalad to caudad is observed in the thoracic segments. A 500 gm-cm trauma at the T-5 or C-7 spinal cord segment did not demonstrate any significant increase in NE levels measured sequentially over a 4-hour period after trauma. Dopamine levels could not be detected in the nontraumatized or traumatized cat spinal cords. Four traumatized cats treated with alpha methyl tyrosine, a tyrosine hydroxylase inhibitor, and followed clinically for 5 months showed no improvement in neurological function when compared to untreated traumatized cats. This study does not support the norepinephrine hypothesis of experimental spinal cord trauma.

The denticulate ligament: anatomy and functional significance

2001 ◽  
Vol 94 (2) ◽  
pp. 271-275 ◽  
Author(s):  
R. Shane Tubbs ◽  
George Salter ◽  
Paul A. Grabb ◽  
W. Jerry Oakes
Keyword(s):  
Spinal Cord ◽  
Functional Significance ◽  
Spinal Canal ◽  
Cervical Region ◽  
Content Type ◽  
Functional Studies ◽  
Applied Tension ◽  
Limited Degree ◽  
Formalin Fixed ◽  
Fine Print

Object. The authors conducted a study to examine the detailed anatomy of the denticulate ligaments and to assess their classic role in spinal cord stability within the spinal canal. Methods. Detailed observation of the denticulate ligaments in 12 adult cadavers was performed. Stress was applied in all major planes to discern when the ligaments would become taut, and at the same time, gross motion of the cord was observed at sites distal to the stresses applied. Tension necessary for avulsion of the ligaments in various areas of the spinal cord was also measured. Conclusions. These results show that the denticulate ligaments do not inhibit cord motion to such discrete areas of the cord as was once thought. The authors have determined that the ligaments are stronger in the cervical region and that they decrease in strength as the spinal cord descends. These findings are demonstrative of the denticulate ligaments being more resistant to caudal compared with cephalad stresses in the cord. Anterior and posterior motion is constrained by these ligaments but to a limited degree, especially as one descends inferiorly along the cord. Further embryological and functional studies of these ligaments is needed in non—formalin fixed tissues.

Pathological basis of spinal cord cavitation in syringomyelia: analysis of 105 autopsy cases

1995 ◽  
Vol 82 (5) ◽  
pp. 802-812 ◽  
Author(s):  
Thomas H. Milhorat ◽  
Anthony L. Capocelli ◽  
Archinto P. Anzil ◽  
Rene M. Kotzen ◽  
Robert H. Milhorat
Keyword(s):  
Spinal Cord ◽  
Subarachnoid Space ◽  
Fourth Ventricle ◽  
Spastic Paraparesis ◽  
Central Canal ◽  
Spinal Cord Tissue ◽  
Content Type ◽  
Age Related ◽  
Spinal Subarachnoid Space ◽  
Fine Print

✓ This report summarizes neuropathological, clinical, and general autopsy findings in 105 individuals with nonneoplastic syringomyelia. On the basis of detailed histological findings, three types of cavities were distinguished: 1) dilations of the central canal that communicated directly with the fourth ventricle (47 cases); 2) noncommunicating (isolated) dilations of the central canal that arose below a syrinx-free segment of spinal cord (23 cases); and 3) extracanalicular syrinxes that originated in the spinal cord parenchyma and did not communicate with the central canal (35 cases). The incidence of communicating syrinxes in this study reflects an autopsy bias of morbid conditions such as severe birth defects. Communicating central canal syrinxes were found in association with hydrocephalus. The cavities were lined wholly or partially by ependyma and their overall length was influenced by age-related stenosis of the central canal. Noncommunicating central canal syrinxes arose at a variable distance below the fourth ventricle and were associated with disorders that presumably affect cerebrospinal fluid dynamics in the spinal subarachnoid space, such as the Chiari I malformation, basilar impression, and arachnoiditis. These cavities were usually defined rostrally and caudally by stenosis of the central canal and were much more likely than communicating syrinxes to dissect paracentrally into the parenchymal tissues. The paracentral dissections of the central canal syrinxes occurred preferentially into the posterolateral quadrant of the spinal cord. Extracanalicular (parenchymal) syrinxes were found typically in the watershed area of the spinal cord and were associated with conditions that injure spinal cord tissue (for example, trauma, infarction, and hemorrhage). A distinguishing feature of this type of cavitation was its frequent association with myelomalacia. Extracanalicular syrinxes and the paracentral dissections of central canal syrinxes were lined by glial or fibroglial tissue, ruptured frequently into the spinal subarachnoid space, and were characterized by the presence of central chromatolysis, neuronophagia, and Wallerian degeneration. Some lesions extended rostrally into the medulla or pons (syringobulbia). Although clinical information was incomplete, simple dilations of the central canal tended to produce nonspecific neurological findings such as spastic paraparesis, whereas deficits associated with extracanalicular syrinxes and the paracentral dissections of central canal syrinxes included segmental signs that were referable to affected nuclei and tracts. It is concluded that syringomyelia has several distinct cavitary patterns with different mechanisms of pathogenesis that probably determine the clinical features of the condition.

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

1998 ◽  
Vol 88 (5) ◽  
pp. 874-883 ◽  
Author(s):  
Stanley A. Baldwin ◽  
Richard Broderick ◽  
David Osbourne ◽  
Georg Waeg ◽  
Deborah A. Blades ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Protein Complex ◽  
Synaptic Function ◽  
Motor Deficits ◽  
Spinal Cord Tissue ◽  
Injury Site ◽  
Content Type ◽  
Spinal Cord Contusion ◽  
Fine Print

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.

Ischemia in primate spinal cord injury

1971 ◽  
Vol 34 (5) ◽  
pp. 614-617 ◽  
Author(s):  
George E. Locke ◽  
David Yashon ◽  
Robert A. Feldman ◽  
William E. Hunt
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lactic Acid ◽  
Rhesus Monkeys ◽  
Spinal Cord Tissue ◽  
Time Intervals ◽  
Content Type ◽  
Lactate Accumulation ◽  
Cord Injury ◽  
Fine Print

✓ Lactate accumulation in spinal cord tissue following trauma was determined to ascertain the role and magnitude of ischemia. High thoracic and low thoracic laminectomies were performed on each of nine rhesus monkeys. The lower exposed cord was traumatized with a calibrated blow of 300 gm cm. The upper exposed cord served as a nontraumatized control. At time intervals of 1.5 min to 48 hrs after trauma, both cord segments were removed and assayed for lactic acid. Lactate in nontraumatized segments averaged 3.64 mM/kg tissue, with a range of 2.20 to 4.95. Lactate in traumatized segments removed in from 1.5 min to 12 hrs from six monkeys averaged 5.50 mM/kg tissue, with a range of 4.32 to 6.46. Lactate in traumatized segments from three monkeys 18 to 40 hrs after trauma averaged 4.07 mM/kg, with a range of 3.20 to 5.18. This finding supports the concept that ischemia plays a role early in the traumatic process in spinal cord injury.

The mechanism of spinal cord cavitation following spinal cord transection

1977 ◽  
Vol 46 (6) ◽  
pp. 757-766 ◽  
Author(s):  
Chun C. Kao ◽  
Louis W. Chang ◽  
James M. B. Bloodworth
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Spinal Cord Transection ◽  
Spinal Cord Tissue ◽  
Content Type ◽  
Nerve Grafts ◽  
Fine Print

✓ Cavitation adjacent to transection of spinal cords can be successfully eliminated by a second operation 1 week after the initial spinal cord transection. The second operation consists of removal of the necrotic spinal cord tissue, thus producing a gap. Segments of autogenous sciatic nerve are inserted into the gap between the spinal cord stumps. If the spinal cord is injured by retransection at the second operation, cavitation again occurs in the spinal cord stumps resulting in separation of the nerve grafts from the spinal cord. The results of the present experiments support the concept that lysosomal spinal cord autotomy, which causes spinal cord cavitation, is a self-limiting process and that once the spinal cord has completed the autotomy, the process will not occur again unless the spinal cord is again traumatized.

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.

Control of blood flow in the cat spinal cord

1983 ◽  
Vol 58 (5) ◽  
pp. 742-748 ◽  
Author(s):  
Oscar U. Scremin ◽  
Emilio E. Decima
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
White Matter ◽  
Ventral Horn ◽  
Hydrogen Gas ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Tissue ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Fine Print

✓ Spinal cord blood flow (SCBF) and the effect of end-tidal CO2 concentration (ETCO2) on SCBF (CO2 reactivity) were studied in the lumbar spinal cord of cats by means of the hydrogen-clearance technique. Hydrogen gas was administered by inhalation, and its level in spinal cord tissue was estimated amperometrically with small (75 µm) platinum electrodes. The average SCBF's at normocapnia (ETCO2 = 4%) of the ventral horn gray matter and of the white matter at several locations were 43.2 and 16.2 ml·100 gm−1·min−1, respectively. For gray and white matter, the values of CO2 reactivity, estimated by the coefficient of the regression of SCBF (ml·100 gm−1·min−1) on ETCO2 (ml·100 ml−1) were 11.6 and 2.1, respectively. No differences in SCBF or CO2 reactivity were observed between intact animals kept under N2O-O2 ventilation and decerebrated animals with no anesthesia. After an acute spinal section, ventral horn SCBF and CO2 reactivity (measured eight segments below the cordotomy) were not altered, in spite of the profound neural depression present (that is, spinal shock). Orthodromic (dorsal root) stimulation of the ventral horn neurons induced an average increase in blood flow of 128% above control values. Antidromic (ventral root) motoneuron activation failed to produce any significant changes in ventral horn blood flow.

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