A mitochondrial lesion in experimental spinal cord trauma

1978 ◽  
Vol 48 (3) ◽  
pp. 434-442 ◽  
Author(s):  
Terifumi Ito ◽  
Norman Allen ◽  
David Yashon

✓ Cytochrome oxidase activities were determined by a microspectrophotometric method on microdissected samples of gray and white matter from frozen-dried sections of dog spinal cord. Experimental animals received 400 gm-cm impact at the T-3 to T-4 level. Sections for enzyme analysis and histological study were taken at the center of the trauma site, at successive 1-mm distances from the center, and at non-traumatized segments. A drop in cytochrome oxidase activities to approximately 50% of normal value was found as early as 15 minutes post-trauma, with greatest decrease at the trauma center and lesser effects at successive distances. This effect was related to known morphological defects in mitochondrial cristae and inner membranes. The enzyme change was significantly correlated with histological estimates of gray matter and neuronal damage, but was also partially independent of these processes. A small but significant increase of enzyme activity in white matter at the trauma site was considered most likely attributable to mitochondrial accumulations due to impaired axoplasmic flow.

1971 ◽  
Vol 35 (6) ◽  
pp. 700-708 ◽  
Author(s):  
Thomas B. Ducker ◽  
Glenn W. Kindt ◽  
Ludwig G. Kempe

✓ This study shows that spinal cord pathology secondary to acute trauma in monkeys evolves with stepwise sequential changes. The acute damage is more central than peripheral. Depending on the amount of trauma, the subacute damage may be limited to central gray necrosis or may progress or evolve to include the neighboring white matter. These pathological changes may be taking place even in the presence of clinical improvement.


2001 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Isabel Zurita

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.


1980 ◽  
Vol 53 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Diana Dow-Edwards ◽  
Vincent DeCrescito ◽  
John J. Tomasula ◽  
Eugene S. Flamm

✓ A study of the effects of spinal cord injury upon spinal cord blood flow was carried out in cats. A 400 gm-cm impact produced an overall reduction in spinal cord blood flow of 24% in the white matter and 30% in the gray matter, as determined by 14C-antipyrine autoradiography. At the level of the injury, white-matter flow was 8.1 ml/100 gm/min, a reduction of 49%, and in the gray matter, 12.5 ml/100 gm/min, a reduction of 76%. Treatment with aminophylline and isoproterenol improved the overall blood flow in the spinal cord. At the level of the injury, white-matter flow after this treatment was no longer significantly different from control values. The gray-matter flow remained decreased to 26.2 ml/100 gm/min, a reduction of only 47%. It is proposed that aminophylline and isoproterenol may increase cyclic adenosine monophosphate (AMP) and prevent platelet aggregation along the endothelial surfaces of the microcirculation, and may thereby help to maintain improved perfusion of the injured spinal cord.


1976 ◽  
Vol 45 (6) ◽  
pp. 660-676 ◽  
Author(s):  
Alan N. Sandler ◽  
Charles H. Tator

✓ Spinal cord blood flow (SCBF) was measured in 24 rhesus monkeys after injury to the cord produced by the inflatable circumferential extradural cuff technique. Measurement of regional blood flow in the white and gray matter of the cord in areas of 0.1 sq mm was achieved with the 14C-antipyrine autoradiographic technique and a scanning microscope photometer. After moderate cord injury (400 mm Hg pressure in the cuff maintained for 5 minutes), which produced paraplegia in 50% of animals and moderate to severe paresis in the other 50%, mean white matter SCBF was significantly decreased for up to 1 hour. White matter blood flow then rose to normal levels by 6 hours posttrauma and was significantly increased by 24 hours posttrauma. Gray matter SCBF was significantly decreased for the entire 24-hour period post-trauma. After severe cord injury (150 mm Hg pressure in the cuff maintained for 3 hours), which produced total paraplegia in almost all animals, SCBF in white and gray matter was reduced to extremely low levels for 24 hours posttrauma. In addition, focal decreases in SCBF were seen in white and gray matter for considerable distances proximal and distal to the injury site. It is concluded that acute compression injury of the spinal cord is associated with long-lasting ischemia in the cord that increases in severity with the degree of injury.


1978 ◽  
Vol 48 (2) ◽  
pp. 239-251 ◽  
Author(s):  
Andrew J. K. Smith ◽  
Douglas B. McCreery ◽  
James R. Bloedel ◽  
Shelley N. Chou

✓ The authors present the results of a controlled, randomized study of alterations in spinal cord blood flow, CO2 responsiveness, and autoregulation following experimental spinal cord injury in cats. Permanent paraplegia is shown to be associated with persistent hyperemia, loss of CO2 responsiveness, and impaired autoregulation in the white matter at the injury site. Probable mechanisms underlying these changes in spinal cord vasomotor control are discussed. Marked similarities between vascular responses of injured spinal cord and luxury perfusion of the brain are pointed out.


2001 ◽  
Vol 95 (2) ◽  
pp. 202-207 ◽  
Author(s):  
Henri-Dominique Fournier ◽  
Philippe Mercier ◽  
Philippe Menei

Object. Because central nervous system white matter exerts a powerful inhibitory effect on axonal growth, implantation of nerve grafts or rootlets into the cervical spinal cord following ventral root avulsion injury should, ideally, be performed directly through the ventral root exit zone (VRExZ), which is located near the anteromedial aspect of the anterior horn; the grafts/rootlets should not be implanted into the white matter of the lateral cord. This is not possible when using a conservative posterior approach. Therefore, the authors have studied the anatomy encountered when using the anterolateral approach and evaluated the technique in the particular case of avulsed ventral nerve roots. They also present a case illustration of the procedure, which is used currently in their department. Methods. Anterior access to the rootlets is obtained using a lateral interscalenic approach; the vertebral artery is exposed and mobilized, and oblique drilling of the vertebral bodies (VBs) is performed. Because the articular processes and half of the VBs are preserved, fusion is not required. The approach allows the surgeon to expose the anterior aspect of the cervical dura and the entire length of the emerging spinal nerves. The anterior aspect of the dura is opened at the desired levels for VRExZ exposure, and the position is ideal for implantation of the graft/rootlets. The interscalenic dissection is mandatory so that the lesions of the supraclavicular plexus can be evaluated and repaired. If necessary, the anterior approach allows for exploration of the infraclavicular plexus during the same procedure. Conclusions. The use of a true anterior approach to the ventral rootlets appears to be a valuable and appropriate approach that avoids extensive laminectomy/facetectomy while reimplantation is performed through the anterolateral sulcus itself. In this approach, however, reimplantation of dorsal roots into the spinal cord remains impossible.


1996 ◽  
Vol 84 (2) ◽  
pp. 234-243 ◽  
Author(s):  
Carel F. E. Hoffmann ◽  
Enrico Marani ◽  
J. Gert van Dijk ◽  
Wim V. D. Kamp ◽  
Ralph T. W. M. Thomeer

✓ Spinal nerve root avulsions frequently occur in brachial plexus injuries caused by traction. Such lesions are considered to afflict the central nervous system (CNS) and are, therefore, believed to be beyond surgical repair. The present experimental study was initiated to challenge this hypothesis. The ventral rootlets of C-7 were avulsed from the spinal cord in 28 cats via an anterior approach and subsequently reimplanted into the cord at the site of origin. In nonoperated control cats and cats undergoing reimplantation, electrophysiological experiments were performed and horseradish peroxidase was administered to the spinal nerve on the reimplanted side after survival times ranging from 6 to 293 days. Spinal cord sections in all cats were stained for neurofilament, acetylcholinesterase (AChE), Nissl, and glial fibrillary acidic protein. Horseradish peroxidase—labeled ventral horn motoneurons were found as early as 14 days after reimplantation and their number increased with time. On Days 209 and 293, the number of labeled neurons equaled the number of labeled ventral horn neurons in the two control cats that did not undergo surgery. Starting on Day 6 after reimplantation, the appearance of the ventral horn and the white matter in the neurofilament, AChE, and Nissl-stained sections changed as a result of the CNS response to the injury. A return to their normal appearance could be observed in these stainings from Day 209 onward. Glial fibrillary acidic protein—positive astrocytic tissue was consistently found in the ventral horn and in the white matter reimplantation area. From Day 69 onward, electrophysiological stimulation of the spinal nerve C-7 on the reimplanted side elicited an electromyogram response in the spinodeltoid muscle. The latency and threshold intensity of the C-7 responses were initially increased but equalized to match the nonoperated controls between 98 and 122 days after reimplantation. The results of this study show that functional regeneration of ventral horn neurons after root avulsion and subsequent reimplantation in the cat is possible.


1982 ◽  
Vol 56 (3) ◽  
pp. 350-358 ◽  
Author(s):  
Eugen J. Dolan ◽  
Charles H. Tator

✓ Posttraumatic spinal cord blood flow (SCBF) was assessed after elevating the mean systemic arterial pressure (mSAP) with a blood transfusion, or with an infusion of dopamine. The effect of the anesthetic agent, gamma hydroxybutyrate, was also assessed. Flows were measured using the 14C-antipyrine autoradiographic method. Animals were injured at T-1 by acute compression of the spinal cord with a clip exerting a pressure of 175 gm. Uninjured animals, with mSAP's of 120.0 ± 17.0 mm Hg, had gray and white matter flows of 74.2 ± 22.3 and 18.7 ± 6.7 ml/100 gm/min, respectively, while injured untreated animals had mSAP's of 82.5 ± 14.1 mm Hg and gray and white matter flows of 13.3 ± 12.1 and 3.9 ± 3.9 ml/100 gm/min, respectively, at the injury site. Blood transfusion raised the mSAP's to 127.5 ± 13.7 mm Hg in the injured animals and doubled the flows in gray and white matter to 25.6 ± 30.2 and 6.3 ± 6.4 ml/100 gm/min, respectively. Dopamine did not have as beneficial an effect as blood transfusion on either the mSAP (101.0 ± 16.7 mm Hg) or the SCBF (gray and white matter flows of 18.4 ± 12.4 and 5.8 ± 5.9 ml/100 gm/min). Gamma hydroxybutyrate (GHB) had almost no effect on the mSAP or SCBF of normal animals, and in injured animals produced only a unilateral increase in flow on the less severely injured side, without affecting the mSAP.


1980 ◽  
Vol 52 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Wise Young ◽  
John Tomasula ◽  
Vincent DeCrescito ◽  
Eugene S. Flamm ◽  
Joseph Ransohoff

✓ Vestibulospinal tract function was monitored in experimental contusion of the spinal cord in cats, and compared with somatosensory cortical evoked potentials. Both white and gray matter portions of the vestibular and somatosensory pathways were evaluated in cord injuries at T-7 and L-4. Severe contusions of 20 gm–20 cm force impact resulted in a rapid (less than 1 second) abolition of thoracic white matter conductivity, but a somewhat slower (4 to 5 minutes) loss of lumbar gray matter responses. A paradoxical transient recovery of white matter conductivity occurred 1 to 2 hours after injury, despite eventual progression to central hemorrhagic necrosis at the contusion site. In contrast, mild contusions (20 gm–10 cm force impact) produced only a temporary loss of neuronal activity: white matter for 1 to 2 hours, and gray matter for 30 to 40 minutes. In general, vestibular and somatosensory potentials showed similar sensitivity to contusion, although the former tended to recover earlier. We conclude that contusion injury causes two types of neuronal dysfunction in spinal cord: 1) a low-threshold concussion-related loss of activity lasting 30 to 120 minutes; and 2) a higher threshold necrotic process, requiring 1 to 2 hours to develop, which apparently spreads from gray to white matter.


1972 ◽  
Vol 36 (4) ◽  
pp. 407-415 ◽  
Author(s):  
George J. Dohrmann ◽  
Franklin C. Wagner ◽  
Paul C. Bucy

✓ The white matter of the monkey spinal cord was examined by electron microscopy during the first 4 hours following a contusion sufficient to produce a transitory paraplegia. At 5 min after injury the myelinated nerve fibers resembled those of the control animals. By 15 and 30 min after contusion, selected fibers were noted to have moderately enlarged periaxonal spaces. Attenuated myelin sheaths, splaying of the myelin lamellae, and a marked increase in the periaxonal spaces were present in affected nerve fibers at 1 hr following trauma. By 4 hrs after contusion approximately one-fourth of the fibers showed breakage of the myelin sheaths and consequent denuding of axons or marked attenuation of the myelin sheaths, greatly enlarged periaxonal spaces, and degeneration of the associated axons.


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