The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury

1989 ◽  
Vol 71 (3) ◽  
pp. 403-416 ◽  
Author(s):  
Michael G. Fehlings ◽  
Charles H. Tator ◽  
R. Dean Linden
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Compression Injury ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Dextran 40 ◽  
Treatment Groups ◽  
Cord Injury ◽  
Fine Print

✓ There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the administration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and improve axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40. The preinjury physiological parameters, including the SCBF at T-1 (mean ± standard error of the mean: 56.84 ± 4.51 ml/100 gm/min), were not significantly different (p > 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 ± 2.99 ml/100 gm/min; p < 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p < 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p < 0.0001), and the SSEP (p < 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 ± 6.09 ml/100 gm/min; p < 0.003) and improved the MEP-C (p < 0.0001), MEP-N (p < 0.04), and SSEP (p < 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p < 0.0001) and somatosensory tracts (p < 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI.

The effect of spinal distraction on regional spinal cord blood flow in cats

1980 ◽  
Vol 53 (6) ◽  
pp. 756-764 ◽  
Author(s):  
Eugen J. Dolan ◽  
Ensor E. Transfeldt ◽  
Charles H. Tator ◽  
Edward H. Simmons ◽  
Kenneth F. Hughes
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Cord Blood ◽  
Spinal Cord Injuries ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Cord Injury ◽  
Autoradiographic Technique ◽  
Fine Print

✓ Distraction is considered to be a factor in many spinal cord injuries. With a specially designed distraction apparatus and the 14C-antipyrine autoradiographic technique, the effect of distraction on spinal cord blood flow (SCBF) in cats was studied. Distraction was performed at L2–3 at a rate of 0.25 cm/10 min, and the spinal evoked response (SER) was monitored by stimulating the sciatic nerve and recording at T-13. The SCBF was assessed in five control animals, four animals in whom the SER was markedly altered by distraction, and five animals after the SER had been abolished and an additional 0.5 cm distraction applied. Control cats had gray- and white-matter flows of 44.5 ± 1.4 (SEM) and 10.5 ± 0.4 ml/100 gm/min, respectively. Distraction to the point of marked SER alteration caused a 50% loss of SCBF at and caudal to the distraction site. An additional 0.5 cm distraction produced total abolition of SCBF at the distraction site and for a considerable distance rostral and caudal to it. Thus, it is shown that spinal distraction causes cord ischemia similar to that seen with other types of spinal cord injury. In addition, distraction severe enough to cause loss of the SER has already produced severe cord ischemia.

Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats

2000 ◽  
Vol 93 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Masahito Hara ◽  
Masakazu Takayasu ◽  
Kazuhiko Watanabe ◽  
Atsushi Noda ◽  
Teruhide Takagi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Protein Kinase ◽  
Treated Group ◽  
Neurological Recovery ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Protein Kinase Inhibition ◽  
Cord Injury ◽  
Fine Print

Object. In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor, is widely administered to prevent vasospasm in patients after subarachnoid hemorrhage. The effects of fasudil on experimental spinal cord injury (SCI) were investigated and compared with those obtained using methylprednisolone. Methods. Spinal cord contusion was induced in rats by applying an aneurysm clip extradurally to the spinal cord at T-3 for 1 minute. After injury three groups of rats were treated with intravenously administered saline (control), intraperitoneally administered fasudil (10 mg/kg), or intravenously administered methylprednisolone (four 30 mg/kg injections). Neurological recovery was evaluated periodically over 1 month by using a modified combined behavioral scale and histopathological examination. Leukocyte infiltration near the injury site was evaluated by measuring myeloperoxidase (MPO) activity at 24 hours. Spinal cord blood flow was measured at intervals up to 3 hours after injury by using laser Doppler flowmetry. In rats in the fasudil-treated group significant improvement in modified combined behavioral score was demonstrated at each time point, whereas in the methylprednisolone-treated rats no beneficial effects were shown. In the fasudil-treated group, reduction of traumatic spinal cord damage was evident histologically in the caudal portion of the injured areas, and tissue MPO activity in tissue samples was reduced. Spinal cord blood flow was not significantly different between fasudiltreated and control group rats. Conclusions. Fasudil hydrochloride showed promise of effectiveness in promoting neurological recovery after traumatic SCI. Possible mechanisms of this effect include protein kinase inhibition and decreased infiltration by neutrophils.

Spinal blood flow in 24-hour megadose glucocorticoid treatment in awake pigs

2003 ◽  
Vol 99 (3) ◽  
pp. 286-290
Author(s):  
Wolf R. Drescher ◽  
Karen P. Weigert ◽  
Mathias H. Bünger ◽  
Ebbe S. Hansen ◽  
Cody E. Bünger
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Body Weight ◽  
High Dose ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Methylprednisolone Treatment ◽  
Fine Print

Object. Because of the controversy regarding the benefits of 24-hour administration of methylprednisolone in patients with spinal cord injury (SCI), it is important to investigate its mechanism of action and side effects. This study was conducted to determine if high-dose methylprednisolone modulates neural and vertebral blood flow in an awake large-sized animal model without SCI. Methods. From a group of 18 immature female domestic pigs born to nine different litters, nine animals were randomly allocated to receive methylprednisolone treatment, whereas their nine female siblings served as controls. Drug or placebo was applied in a blinded fashion by a third person not involved in the study. The following treatment for SCI, as suggested by the North American Spinal Cord Injury Study, was administered to the awake pig: methylprednisolone (30 mg/kg of body weight) was infused into the jugular vein during a 15-minute period, followed by a 45-minute pause, and the infusion was maintained over a 23-hour period at a dose of 5.4 mg/kg body weight/hour. By means of the radioactive tracer microsphere technique, spinal cord blood flow (SCBF) was measured in the awake standing pig in the cerebrum, and in spinal gray and white matter, nerve roots, endplates, cancellous bone, cortical shell, and T12—L2 discs. Blood flow was measured before, 1 hour after initiation of infusion, and 24 hours postinfusion. Examination of blood flow in the neural and vertebral tissue samples, as well as of central hemodynamics, revealed no significant difference between the experimental and control groups, and this parity was maintained throughout the experimental phases. Conclusions. In the awake pig model, 24-hour methylprednisolone treatment does not modulate cerebral or SCBF, nor does it increase the risk for vertebral osteonecrosis by producing vertebral ischemia.

Regional spinal cord blood flow in rats after severe cord trauma

1978 ◽  
Vol 49 (6) ◽  
pp. 844-853 ◽  
Author(s):  
Alex S. Rivlin ◽  
Charles H. Tator
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Gray Matter ◽  
Albino Rats ◽  
Compression Injury ◽  
Spinal Cord Blood Flow ◽  
Compression Technique ◽  
Content Type ◽  
Cord Injury

✓ Spinal cord blood flow (SCBF) was measured in 12 albino rats following acute cord injury produced by the extradural clip compression technique. Severe injury was produced with the clip compressing the cord with a force of 180 gm for 5 minutes, an injury previously shown to produce a severe functional deficit. Regional SCBF was measured 15 minutes, 2 hours, and 24 hours after injury by the 14C-antipyrine autoradiographic technique and a scanning microscope photometer. At 15 minutes and 2 hours, white and gray matter blood flow was severely diminished, and, at 24 hours, there was only minimal improvement. Focal decreases in blood flow were seen in white and gray matter for a considerable distance proximal and distal to the site of cord trauma. Thus, it has been confirmed in this model that severe cord compression injury produces severe posttraumatic ischemia in the cord which lasts for at least 24 hours.

Effect of acute spinal cord compression injury on regional spinal cord blood flow in primates

1976 ◽  
Vol 45 (6) ◽  
pp. 660-676 ◽  
Author(s):  
Alan N. Sandler ◽  
Charles H. Tator
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
White Matter ◽  
Cord Blood ◽  
Gray Matter ◽  
Regional Blood Flow ◽  
Compression Injury ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Cord Injury

✓ 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.

Failure of Naloxone to Improve Spinal Cord Blood Flow and Cardiac Output after Spinal Cord Injury

Neurosurgery ◽  
1986 ◽  
Vol 18 (4) ◽  
pp. 428-432 ◽  
Author(s):  
Christopher M. Wallace ◽  
Charles H. Tator
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Cardiac Output ◽  
Cord Blood ◽  
Systemic Arterial Pressure ◽  
Compression Injury ◽  
Spinal Cord Blood Flow ◽  
Progressive Decline ◽  
Cord Injury

Abstract It has been reported that the narcotic antagonist, naloxone, can improve spinal cord blood flow (SCBF) and clinical recovery after experimental spinal cord injury produced by the weight-dropping technique. The purpose of the present study was to determine the effect of naloxone on SCBF, cardiac output (CO) and blood flow to other organs following clip compression injury. Rats were anesthetized, paralyzed and ventilated, with mean systemic arterial pressure (MSAP) recorded continuously, After a C-7-T-1 laminectomy and a 1-minute acute compression injury with a 50-g clip at T-1, rats were given injections of radioactive microspheres for measurement of SCBF, CO, and blood flow to other organs. The first determination was made 15 minutes after injury and a second was made after a 1-hour treatment with naloxone. Treated animals each received an intravenous bolus injection of naloxone (10 mg/kg) followed by a 1-hour intravenous infusion (2 mg/kg/hour). Naloxone failed to improve posttraumatic SCBF in the injured spinal cord. In addition, naloxone did not prevent posttraumatic hypotension or the progressive decline in CO seen between 15 and 75 minutes after injury. Thus, this study does not support the previous claims of a beneficial effect of naloxone on posttraumatic SCBF and MSAP.

Effect of aluminum on neurological recovery in rats following spinal cord injury

2000 ◽  
Vol 93 (2) ◽  
pp. 276-282 ◽  
Author(s):  
Khalaf Al Moutaery ◽  
Saleh Al Deeb ◽  
Nabil Biary ◽  
Christudas Morais ◽  
Haseeb Ahmad Khan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Deficit ◽  
Sprague Dawley ◽  
Compression Injury ◽  
Content Type ◽  
Sensory Score ◽  
Cord Injury ◽  
Histopathological Studies ◽  
Fine Print

Object. This investigation was undertaken to study the effect of aluminum on neurobehavioral, electrophysiological, structural, and biochemical changes in rats following spinal cord injury (SCI). Methods. Adult male Sprague—Dawley rats classified into different groups were given aluminum sulfate—dosed drinking water in the concentrations of 0%, 0.25%, 0.5% and 1%, respectively. After 30 days of aluminum treatment, the animals were subjected to spinal cord trauma. Laminectomy was performed at T7–8 in anesthetized rats, followed by placement of a compression plate (2.2 × 5 mm) loaded with a 35-g weight over the exposed spinal cord for 5 minutes. Control animals underwent the same surgical procedure, but the compression injury was not induced (sham). Postoperative neurological function was assessed using the inclined-plane test and by obtaining a modified Tarlov score and vocal/sensory score daily for 10 days. Electrophysiological changes were assessed using corticomotor evoked potentials, whereas pathological changes were assessed by light microscopy. The level of vitamin E in the spinal cord was measured as an index of antioxidant defense. The behavioral, biochemical, and histological analyses were performed in a blinded fashion. Conclusions. Analysis of results obtained in the behavioral studies revealed that the compression of spinal cord produced transient paraparesis in which a maximum motor deficit occurred at Day 1 following SCI and resolved over a period of 10 days. Administration of aluminum significantly impaired the recovery following SCI. Analysis of the results of the biochemical, electrophysiological, and histopathological studies also confirmed the deleterious effects of aluminum on recovery from SCI in rats.

scholarly journals Spinal Cord Blood Flow Measured with Microspheres Following Spinal Cord Injury in the Rat

1986 ◽  
Vol 13 (2) ◽  
pp. 91-96 ◽  
Author(s):  
M. Christopher Wallace ◽  
Charles H. Tator
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Cord Blood ◽  
Systemic Arterial Pressure ◽  
Compression Injury ◽  
Spinal Cord Blood Flow ◽  
Radioactive Microsphere ◽  
Cord Injury ◽  
Radioactive Microsphere Technique

ABSTRACT:A decrease in spinal cord blood flow (SCBF) is a known sequela of spinal cord injury. The radioactive microsphere technique permits repeated measurement of spinal cord blood flow (SCBF) and cardiac output (CO) in the same experimental animal. The purpose of this study was to adapt the radioactive microsphere technique for use in the rat extradural clip compression injury model used in our laboratory.Thirteen adult Wistar rats were anaesthetized and ventilated. Mean systemic arterial pressure (MSAP) was recorded continuously. Control animals (n = 8) did not have a surgical procedure whereas the injured animals (n = 5) underwent a C7-T1 laminectomy followed by a one minute, 50 gram extradural clip compression injury at Tl. Radioactive microspheres were used for two blood flow and CO determinations in both groups.MSAPfell 59% in the injured animals (p<0.01), but this was not accompanied by significant changes in heart rate or CO. There was a 50% reduction in SCBF in the injured cord (p<0.02), and there were significant reductions in cerebral blood flow (p<0.05) and cerebellar blood flow (p<0.02) following spinal cord injury.

Mexiletine treatment—induced inhibition of caspase-3 activation and improvement of behavioral recovery after spinal cord injury

2005 ◽  
Vol 3 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Hakan Caner ◽  
Ihsan Solaroglu ◽  
Kamer Kilinc
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Single Dose ◽  
Caspase 3 ◽  
Cellular Damage ◽  
Behavioral Recovery ◽  
Content Type ◽  
Treatment Groups ◽  
Cord Injury ◽  
Fine Print

Object. It has been demonstrated in several experimental studies that apoptosis contributes to cellular damage after spinal cord injury (SCI). During apoptosis dying cells secrete additional mediators of apoptosis such as cytokines and free radicals which have additional toxic effects and exacerbate neuronal death. The aim of this laboratory study was to investigate the effects of mexiletine on caspase-3 activation and functional recovery and compare its post-SCI effectiveness with methylprednisolone. Methods. The rats were divided into five groups. Animals in the trauma group underwent traumatic interventions after laminectomy. Spinal cord contusion injury was produced using the weight-drop method. Animals in treatment groups received a single dose of methylprednisolone sodium succinate (Group C), single dose of mexiletine (Group D), or vehicle solution (saline; Group E) intraperitoneally immediately after injury. Hind-limb functions were assessed using the inclined plane technique and caspase-3 activity in tissue samples was measured 24 hours after SCI. Traumatic injury was found to increase tissue caspase-3 activity. In both treatment groups the drug prevented an increase in caspase-3 activity. Mexiletine treatment improved early behavioral recovery after SCI. Conclusions. The results obtained in this study demonstrated that mexiletine treatment inhibits caspase-3 activation and preserve/restore better neuronal function compared with methylprednisolone after experimental SCI.

Review of the effect of spinal cord trauma on the vessels and blood flow in the spinal cord

1976 ◽  
Vol 45 (6) ◽  
pp. 638-646 ◽  
Author(s):  
Alan N. Sandler ◽  
Charles H. Tator
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
White Matter ◽  
Species Variation ◽  
Spinal Cord Trauma ◽  
Compression Injury ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

✓ The effect of spinal cord trauma on the vasculature and blood flow of the spinal cord is reviewed. Both quantitative and nonquantitative studies are critically discussed and reasons sought for some of the major controversies that have arisen. Differences in methodology, species variation, and variation in the degree and type of cord injury may all be important factors in producing the conflicting results reported in the literature. In general, it can be said that trauma has a profound effect on the vasculature and blood flow in the cord and that severe compression injury of the cord causes marked ischemia in the gray and white matter.

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