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Objectives: Delayed paraplegia developed postoperatively after thoracoabdominal aneurysm surgery is primarily associated with spinal cord ischemia/reperfusion injury. Our previous study suggested that spinal cord stimulation postconditioning protected the spinal cord from ischemia/reperfusion injury through microglia inhibition. In this study, we further investigated whether α7 nicotinic acetylcholine receptors were involved in the neuroprotective mechanism of spinal cord stimulation., Methods: Rabbits were randomly assigned to sham, control, 2 Hz, α-bungarotoxin, and 2 Hz-α-bungarotoxin groups (n = 24/group). Transient spinal cord ischemia was performed on all rabbits except rabbits in the sham group. Rabbits in the control group received no further intervention, rabbits in the 2 Hz group were given 2 Hz spinal cord stimulation, rabbits in the α-bungarotoxin group received prescribed intrathecal α-bungarotoxin (α-bungarotoxin, a specific α7 nicotinic acetylcholine receptor antagonist) injections, and rabbits in the 2 Hz-α-bungarotoxin group received both α-bungarotoxin injections and 2 Hz spinal cord stimulation. Hind-limb neurologic function was assessed, and spinal cord histologic examination, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and microglia staining were performed at 8 hours, 1 day, 3 days, and 7 days of reperfusion., Results: Rabbits in the 2 Hz group had significantly better neurologic functions, more α-motor neurons, and lower terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive neuron rates and microglia area/anterior horn area ratios (microglia area ratios) than the control group. The neurologic functions of the α-bungarotoxin group were significantly worse than those of the control group, whereas other results were not significantly different from the control group. The results of the 2 Hz-α-bungarotoxin group were insignificant to the control group except for the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive neuron rates, which were significantly lower than in the control group., Conclusions: The neuroprotective effects of spinal cord stimulation postconditioning against spinal cord ischemia/reperfusion injury were partially mediated by activating α7 nicotinic acetylcholine receptors., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: Spinal cord ischemia secondary to trauma or a vascular occlusive event is a threatening phenomenon. The neuroprotective properties of minocycline have been shown in several models of central nervous system diseases and after spinal cord ischemia; however, the benefit of using the drug requires additional confirmation in different animal models. Astrocytes are essential as regulators of neuronal functions and for providing nutrients. The authors hypothesized that astrocytes in the spinal cord may be an important target for minocycline action after ischemia and thus in the prevention of secondary spreading damage., Design: A prospective, randomized animal study., Setting: University research laboratory, single institution., Participants: Adult male Sprague Dawley rats, weighing between 400 and 450 g., Interventions: A model of spinal cord ischemia in the rat was used for this study to determine whether a single, high-dose (10 mg/kg) of minocycline protects against damage to the neuronal cytoskeleton, both in the white and gray matter, and whether it reduces glial fibrillary acidic protein levels, which is an index for prevention of astrocyte activation during ischemia. Thirty minutes before thoracic aorta occlusion, minocycline was administered for 18 minutes using a 2 F Fogarty catheter., Measurements and Main Results: Minocycline given prophylactically significantly mitigated severe hindlimb motor impairment and reduced glial fibrillary acidic protein plus astrocytosis in both the white and gray matter of the spinal cord, caudal to the occlusion. Neuronal histologic cytoarchitecture, which was severely and significantly compromised in control animals, was preserved in the minocycline-treated animals., Conclusions: This study's data imply that minocycline may attenuate reactive astrocytosis in response to injury with better neurologic outcome in a model of spinal cord ischemia in rats. The data suggest that future use of minocycline, clinically, might be advantageous in surgeries with a potential risk for paraplegia due to spinal cord ischemia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Delayed paraplegia complicates the recovery from spinal cord ischemia or traumatic spinal cord injury. While delayed motor neuron apoptosis is implicated in the pathogenesis, no effective treatment or preventive measures is available for delayed paraplegia. Hydrogen sulfide exerts anti-apoptotic effects. Here, we examined effects of hydrogen sulfide breathing on the recovery from transient spinal cord ischemia. Breathing hydrogen sulfide starting 23 h after reperfusion for 5 h prevented delayed paraplegia after 5 min of spinal cord ischemia. Beneficial effects of hydrogen sulfide were mediated by upregulation of anti-apoptotic Bcl-XL and abolished by nitric oxide synthase 2 deficiency. S-nitrosylation of NFkB p65 subunit, which is induced by nitric oxide derived from nitric oxide synthase 2, facilitated subsequent sulfide-induced persulfidation of p65 and transcription of anti-apoptotic genes. These results uncover the molecular mechanism of the anti-apoptotic effects of sulfide based on the interaction between nitric oxide and sulfide. Exploitation of the anti-apoptotic effects of delayed hydrogen sulfide breathing may provide a new therapeutic approach for delayed paraplegia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Prevention of the development of paraplegia during the repair of the damage caused by descending thoracic and thoracoabdominal aneurysms remains an important issue. Therefore, we investigated the protective effect of atorvastatin on ischemia-induced spinal cord injury in a rabbit model., Method: Thirty-two rabbits were divided into the following four equally sized groups: group I (control), group II (ischemia-reperfusion), group III (atorvastatin treatment) and group IV (atorvastatin withdrawal). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs of each animal was evaluated according to the Tarlov score. Spinal cord and blood samples were obtained for histopathological and biochemical analyses., Results: All of the rabbits in group II exhibited severe neurological deficits. Atorvastatin treatment (groups III and IV) significantly reduced the level of motor dysfunction. No significant differences were observed between the motor function scores of groups III and IV at the evaluated time points. Light microscopic examination of spinal cord tissue samples obtained at the 72nd hour of reperfusion indicated greater tissue preservation in groups III and IV than in group II., Conclusion: This study demonstrates the considerable neuroprotective effect of atorvastatin on the neurological, biochemical and histopathological status of rabbits with ischemia-induced spinal cord injury. Moreover, the acute withdrawal of atorvastatin therapy following the induction of spinal cord ischemia did not increase the neuronal damage in this rabbit model.

Objective: To evaluate the role of memantine (N-methyl-d-aspartate receptor antagonist) pretreatment for the prevention of spinal cord ischemia after infrarenal aortic clamping in a rabbit model., Methods: Thirty New Zealand White rabbits were divided into 5 different groups of 6 rabbits. Groups 60-7 and 60-5 received oral memantine 60 mg once a day for 7 and 5 days, respectively, and groups 30-5 and 30-3 received oral memantine 30 mg once a day for 5 and 3 days, respectively, all before surgery. Group C (control) received normal feeds without memantine. A paraplegic model was created by clamping both the aorta and the inferior vena cava infrarenally and just proximal to their bifurcations for 45 minutes. The modified Tarlov score, motor evoked potential (MEP), serum memantine concentration, and histopathology of the spinal cord were evaluated., Results: The mean modified Tarlov scores were 4.2±1.3, 4.3±1.0, 4.2±1.3, 4.3±1.2, and 0.8±1.6 in groups 60-7, 60-5, 30-5, 30-3, and C, respectively at 6, 24, 48, and 72 hours (P<.009 for individual groups vs control). Percentage amplitude loss of MEP by the end of surgery was 29.5%±46.3%, 11.9%±28.0%, 30.0%±46.8%, 16.7%±40.8%, and 81.8%±40.3% for the 5 groups, respectively (P=.049). After declamping, MEP reappeared in 83%, 100%, 83%, 83%, and 33% of cases in the 5 groups, respectively (P=.073). The serum memantine level was similar in the 4 memantine groups. Spinal cords were normal in most of the rabbits in groups 60-7, 60-5, 30-5, and 30-3, but severely ischemic in most of the rabbits in group C (P=.041)., Conclusions: Oral memantine pretreatment is protective against spinal cord ischemia, and can be an additional strategy for the prevention of paraplegia during thoracoabdominal aortic surgeries., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: It is well known that ischemic postconditioning reduces ischemic-reperfusion injury, but the underlying mechanism is not fully understood. The current study investigated the role of reactive oxygen species-mediated upregulation of endogenous antioxidant enzymes in the generation of a protective effect induced by ischemic postconditioning against spinal cord reperfusion injury in the rabbit., Methods: New Zealand White rabbits were randomly allocated to sham, ischemia-reperfusion, and postconditioning groups (3 cycles of 30 seconds of reperfusion and 30 seconds of occlusion during the onset of reperfusion). Spinal cord ischemia was induced by clamping the infrarenal abdominal aorta for 20 minutes in the ischemia-reperfusion and postconditioning groups. Forty-eight hours after reperfusion, the neurologic status of the lower limbs was assessed. Blood samples were collected for analysis of serum neuron-specific enolase levels, and the lumbar spinal cord segments (L5-7) were harvested for histopathologic and antioxidant enzyme activities and mRNA analysis with or without administration of N-2-mercaptopropionylglycine (an effective oxygen free radical scavenger) given at different reperfusion times., Results: Continuous administration of N-2-mercaptopropionylglycine for 13 minutes, starting at 10 minutes before (but not 10 minutes after) the beginning of reperfusion, attenuated the neuroprotective effect of postconditioning against spinal cord ischemia and reversed the increase in activity of the antioxidant enzymes superoxide dismutase and catalase in spinal cord tissue subjected to ischemic postconditioning., Conclusions: The results indicate that reactive oxygen species-triggered upregulation of endogenous antioxidant enzyme activities may be involved in the mechanism of neuroprotection of ischemic postconditioning., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: A better understanding of the response of the spinal cord blood supply to segmental artery (SA) sacrifice should help minimize the risk of paraplegia after both open and endovascular repair of thoracoabdominal aortic (TAA) aneurysms., Methods: Twelve female juvenile Yorkshire pigs were randomized into 3 groups and perfused with a barium-latex solution. Pigs in group 1 (control) had infusion without previous intervention. Pigs in group 2 were infused 48 hours after ligation of all SAs (T4-L5) and those in group 3 at 120 hours after ligation. Postmortem computed tomographic scanning of the entire pig enabled overall comparisons and measurement of vessel diameters in the spinal cord circulation., Results: We ligated 14.5 ± 0.8 SAs: all filled retrograde to the ligature. Paraplegia occurred in 38% of operated pigs. A significant increase in the mean diameter of the anterior spinal artery (ASA) was evident after SA sacrifice (P < .0001 for 48 hours and 120 hours). The internal thoracic and intercostal arteries also increased in diameter. Quantitative assessment showed an increase in vessel density 48 hours after ligation of SAs, reflected by an obvious increase in small collateral vessels seen on 3-dimensional reconstructions of computed tomographic scans at 120 hours., Conclusions: Remodeling of the spinal cord blood supply--including dilatation of the ASA and proliferation of small collateral vessels--is evident at 48 and 120 hours after extensive SA sacrifice. It is likely that exploitation of this process will prove valuable in the quest to eliminate paraplegia after TAA aneurysm repair., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Spinal cord ischemia belongs to serious and relatively frequent diseases of CNS. The aim of the present study was to find out the vulnerability of nitrergic neurons to 15 min transient spinal cord ischemia followed by 1 and 2 weeks of reperfusion. We studied neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in structural elements of lumbosacral spinal cord along its rostrocaudal axis. In addition, a neurological deficit of experimental animals was evaluated. Spinal cord ischemia, performed on the rabbit, was induced by abdominal aorta occlusion using Fogarty catheter introduced into the right femoral artery for a period of 15 min. After surgical intervention the animals survived for 7 and 14 days. nNOS-immunoreactivity (nNOS-IR) was measured by immunohistochemical and NADPHd-positivity by histochemical method, and both immunohistochemical and histochemical stainings were quantified by densitometric analyses. Neurological deficit was evaluated according Zivin's criteria. The number of nNOS-IR and/or NADPH-d positive neurons and the density of neuropil were markedly increased in superficial dorsal horn (laminae I-III) after 15 min ischemia and 7 days of reperfusion. However, ischemia followed by longer time of survival (14 days) returned the number of nNOS-IR and NADPH-d positive neurons to control. In the pericentral region (lamina X) containing interneurons and crossing fibers of spinal tracts, than in lamina VII and in dorsomedial part of the ventral horn (lamina VIII) we recorded a decreased number of nNOS-IR and NADPH-d positive neurons after both ischemia/reperfusion periods. In the medial portion of lamina VII and dorsomedial part of the ventral horn (lamina VIII) we observed many necrotic loci. This area was the most sensitive to ischemia/reperfusion injury. Fifteen minute ischemia caused a marked deterioration of neurological function of hind limbs, often developing into paraplegia. A quantitative immunohistochemical and histochemical study have shown a strong vulnerability of nitrergic neurons in intermediate zone to transient spinal cord ischemia.

Background and Purpose: Delayed paraplegia remains a devastating complication after ischemic spinal cord injury associated with aortic surgery and trauma. Although apoptosis has been implicated in the pathogenesis of delayed neurodegeneration, mechanisms responsible for the delayed paraplegia remain incompletely understood. The aim of this study was to elucidate the role of apoptosis in delayed motor neuron degeneration after spinal cord ischemia., Methods: Mice were subjected to spinal cord ischemia induced by occlusion of the aortic arch and left subclavian artery for 5 or 9 minutes. Motor function in the hind limb was evaluated up to 72 hours after spinal cord ischemia. Histological studies were performed to detect caspase-3 activation, glial activation, and motor neuron survival in the serial spinal cord sections. To investigate the impact of caspase-3 activation on spinal cord ischemia, outcome of the spinal cord ischemia was examined in mice deficient for caspase-3., Results: In wild-type mice, 9 minutes of spinal cord ischemia caused immediate paraplegia, whereas 5 minutes of ischemia caused delayed paraplegia. Delayed paraplegia after 5 minutes of spinal cord ischemia was associated with histological evidence of caspase-3 activation, reactive astrogliosis, microglial activation, and motor neuron loss starting at approximately 24 to 48 hours after spinal cord ischemia. Caspase-3 deficiency prevented delayed paraplegia and motor neuron loss after 5 minutes of spinal cord ischemia, but not immediate paraplegia after 9 minutes of ischemia., Conclusions: The present results suggest that caspase-3 activation is required for delayed paraplegia and motor neuron degeneration after spinal cord ischemia.

Objective: We have demonstrated that therapeutic augmentation of systemic blood pressure during spinal cord ischemia plays an important role in minimizing spinal cord injury in both experimental and clinical aortic surgery. However, there remain concerns that excessively high blood pressure during spinal cord reperfusion may aggravate the reperfusion injury. The purpose of this study is to investigate the effect of high blood pressure during spinal cord reperfusion on postoperative neurologic outcomes after aortic surgery in rabbits., Methods: Experiments were performed using a rabbit spinal cord ischemia-reperfusion model in 2 randomly divided groups: (1) In the HR group, the mean blood pressure was maintained at a high level (121 +/- 1.3 mm Hg) during reperfusion with intravenously administered phenylephrine; and (2) in the CR group, the mean blood pressure was not medically controlled (75 +/- 9.1 mm Hg) during reperfusion. Neurologic and histologic assessments and evaluation of early reperfusion injury were performed., Results: In the HR group, slow and incomplete recovery of transcranial motor-evoked potentials (P = .02) and low neurologic scores (P < .005) were observed during spinal cord reperfusion compared with the CR group. At 48 hours of reperfusion, there were significantly fewer viable neuron cells, more apoptosis, and more perivascular edema with gray matter vacuolation in the HR group (P < .001 for each). At 3 hours, myeloperoxidase activity (P = .0021), vascular permeability (P = .0012), and superoxide generation (P < .0001) were significantly increased in the HR group., Conclusion: Excessively high blood pressure in the early phase of spinal cord reperfusion increased reperfusion injury in the spinal cord, leading to exacerbation of early-onset paraplegia. Avoidance of spinal cord reperfusion with high blood pressure may be one management strategy in thoracoabdominal aortic surgery., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia., Methods: Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated., Results: Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group., Conclusions: Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Prevention of paraplegia remains an important issue in repair of descending thoracic and thoracoabdominal aneurysms. Therefore, we investigated the protective effect of sivelestat sodium hydrate (ONO-5046) on ischemia-induced spinal cord damage in a rabbit model. Twenty New Zealand white rabbits were divided into two equal groups; ONO-5046 (1.6 mg/kg)+isotonic NaCl (30 ml) was administered selectively to the spinal cord via the lumbar arteries for the first 3 min during 30 min of infra-renal aorta clamping in the experimental group (group E), whereas NaCl was given alone in the control group (group C). Motor function of the lower limbs was assessed two days later by Tarlov criteria. The number of intact motor neurons in the anterior segment of the cord (L5 level) was counted after hematoxylin-eosin staining and the number of apoptotic motor neurons after TUNEL staining. Motor function of the lower limbs in group E was significantly better (P=0.003) than that in group C. The number of intact motor neurons was greater and of apoptotic motor neurons was less in group E than C. Selective infusion of sivelestat sodium hydrate directly into the spinal cord via the lumbar arteries significantly attenuated functional and morphological ischemia-induced spinal cord injury.

We present a patient with subacute progressive paraparesis secondary to intravascular lymphoma restricted to the spinal cord where initial laboratory and imaging studies were inconclusive. We emphasise the importance of a systematic approach to the diagnosis and highlight the utility of spinal cord biopsy to establish the definitive diagnosis of this rare but treatable illness.

Open surgery for thoracic aortic disease is associated with significant morbidity and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%, respectively. Spinal cord ischemia and stroke have also been reported following endoluminal repair. This study reviews the incidence of paraplegia and stroke in a series of 186 patients treated with thoracic stent grafts. From July 1997 to September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty-eight patients were treated electively and 58 patients had urgent procedures. Anesthesia was epidural in 131, general in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.

Background: Traumatic spinal cord infarction was initially described in the era previous to the availability of MRI. This entity occurs in children and affects the thoracic spinal cord, usually presenting as a delayed cord injury. Patients have a high incidence of associated blunt thoracic or retroperitoneal trauma and arterial hypotension at admission. The described mechanism of injury is a traumatic occlusion of the aortic branches nourishing the spinal cord. It shares several characteristics with SCIWORA. In past years, the presence of this injury has received little importance., Case Description: A 5-year-old boy suffered from high-energy blunt trauma over the thoracoabdominal area, presenting hypotension, retroperitoneal injury, and delayed complete thoracic SCI. An MRI showed spinal cord infarction located in the territory of AKA. During subsequent examinations, the boy did not show signs of neurological improvement., Conclusion: It is important to include TSCIf in the diagnosis of children who present delayed SCI (hours to 4-5 days), especially if the injury is located in the thoracic cord and is accompanied by blunt thoracic or abdominal trauma. Because the conventional radiographic tests are normal, TSCIf can be considered as a special type of SCIWORA.

Objective: Severe global ischemia often results in severe damage to the central nervous system of survivors. Hind-limb paralysis is a common deficit caused by global ischemia. Until recently, most studies of global ischemia of the central nervous system have examined either the brain or spinal cord, but not both. Spinal cord damage specifically after global ischemia has not been studied in detail. Because the exact nature of the neuronal damage to the spinal cord and the differences in neuronal damage between the brain and spinal cord after global ischemia are poorly understood, we developed a new global ischemia model in the rat and specifically studied spinal cord damage after global ischemia. Further, we compared the different forms of neuronal damage between the brain and spinal cord after global ischemia., Design: Randomized, controlled study using three different global ischemia models in the rat., Setting: University research laboratory., Subjects: Male, adult Sprague-Dawley rats (300 g)., Interventions: Animals were divided into three experimental groups, group A (n = 6, survived for 7 days), 12 mins of hemorrhagic shock; group B (n = 6, survived for 7 days), 5 mins of cardiac arrest; or group C (n = 6, each for 6 hrs, 12 hrs, 1 day, 3 days, and 7 days), 7 mins of hemorrhagic shock and 5 mins of cardiac arrest. Motor deficit of the hind limbs was studied 6 hrs to 7 days after resuscitation. Also, nonoperated animals (n = 6) were used as the control. Histologic analysis (hematoxylin and eosin, Fluoro-Jade B, terminal deoxynucleotidyl transferase- mediated dUTP end-labeling [TUNEL], Klüver-Barrera) and ultrastructural analysis using electron microscopy were performed on samples from the CA1 region of the hippocampus and lumbar spinal cord. Demyelination of the white matter of the lumbar spinal cord was analyzed semiquantitatively using Scion Image software., Main Results: No paraplegic animals were observed in either group A or B. All group C animals showed severe hind-limb paralysis. Severe neuronal damage was found in the CA1 region of the hippocampus in all groups, and the state of delayed neuronal cell death was similar among the three groups. Neuronal damage in the lumbar spinal cord was detected only in group C animals, mainly in the dorsal horn and intermediate gray matter. Demyelination was prominent in the ventral and ventrolateral white matter in group C. A significant difference was observed between control and group C rats with Scion Image software. Ultrastructural analysis revealed extensive necrotic cell death in the intermediate gray matter in the lumbar spinal cord in group C rats., Conclusion: The combination in the global ischemia model (i.e., hemorrhagic shock followed by cardiac arrest) caused severe neuronal damage in the central nervous system. Thereby, hind-limb paralysis after global ischemia might result from spinal cord damage. These results suggest that therapeutic strategies for preventing spinal cord injury are necessary when treating patients with severe global ischemia.

Background: It has been shown that transplantation of bone marrow stromal cells (MSCs) into the ischemic brain improves functional outcome. We sought to investigate whether intrathecal injection of MSCs can attenuate neurologic injury of spinal cord ischemia., Methods: Rabbit MSCs were expanded in vitro and were pre-labeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion. Group A and control A were subjected to a 20-minute ischemia and the ischemic duration was extended to 30 minutes in group B and control B. Two days before spinal cord ischemia, 1 x 10(8) MSCs were intrathecally injected into groups A and B, whereas vehicle alone was injected into the control groups. Hind-limb motor function was assessed during a 14-day recovery period with Tarlov criteria, and then histologic examination was performed., Results: Marrow stromal cells survived and engrafted into the spinal cord 2 days after transplantation, and more MSCs were found in the lumbar spinal cord (ischemic segment) than in the thoracic spinal cord (nonischemic segment) at 14 days. Compared with their respective control groups, Tarlov scores were significantly higher in both groups A and B (p < 0.05, group A vs control A, at 2, 7, and 14 days; p < 0.05, group B vs control B, at 1, 2, 7, and 14 days, respectively). The number of intact motor neurons was much higher in the two experimental groups (p < 0.01 vs the corresponding control groups, respectively)., Conclusions: Intrathecal injection of MSCs attenuates ischemic injury of spinal cord.

Study Design: The 5 year review of patients referred to one center., Objective: To report spinal cord infarction secondary to vascular occlusion from disease in a lower thoracic intervertebral foramen., Method: The clinical and imaging findings of two cases with acute spinal cord dysfunction are presented., Setting: Midlands Centre for Spinal Injuries, England., Results: The CT and MR imaging features revealed lower thoracic unilateral foraminal occlusion due to acute facet joint septic arthritis in a diabetic patient, and secondary to chronic hypertrophic osteophytes in a second hypertensive individual. The presumed mechanism of infarction was occlusion of the artery of Adamkiewicz., Conclusion: Foraminal disease in the lower thoracic levels needs to be entertained in cases of unexplained nontraumatic acute spinal cord dysfunction.

Paraplegia, which develops after operation on aorta, represents a real catastrophe for the patient and for the surgeon. The aim of the present work was to investigate the light microscopy picture of this complication and consequently better understand related processes. Twenty one adult dogs, cross breeds of both sexes, weight 18-25 kg, were divided into four groups: 1. Controls (n = 3); 2.30-min ischemia induced by occlusion of thoracic aorta by a tourniquet, followed for 30 min survival (n = 6); 3.30-min ischemia and 72 h of survival (n = 6); 4) 30-min ischemia and 6 days of survival (n = 6). All these manipulations were made in sterile conditions under general anesthesia. As soon as the planned time of survival passed, the animals were flushed out, in deep pentobarbital anesthesia, with 3,000 ml of sodium chloride and fixed with 3,000 ml of 10% neutral formaldehyde. Sections, 30 microns thick, from L3-S1 medulla segments were processed in the laboratory of Neurobiological Institute by the method of Nauta for light microscopy examination. Neurohistological picture was characterized by a marked damage of the medulla neurons. The changes proved to be irreversible and resulted, in the course of six days of survival, to death of the cells, characterized by their disintegration. The results indicate that the only rational procedure in conditions of threatening ischemic-reperfusion injury of medulla is to prevent it.

The purpose of this study was to investigate the effect of N-acetylcysteine (NAC) on spinal cord ischemia-reperfusion (I-R) in rabbits. Thirty rabbits were divided into five equal groups, group I (sham-operated, no I-R), group II (control, only I-R), group III (I-R+NAC), group IV (I-R+hypothermia), group V (I-R+NAC+hypothermia). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Forty-eight hours postoperatively, the motor function of the lower limbs was evaluated in each animal according to Tarlov Score. Spinal cord samples were taken to evaluate the histopathological changes. The sham-operated rabbits (group I) showed no neurologic deficit (Score=4). Paraplegia (Score=0) developed in all rabbits in the control group (group II). Administration of 50 mg/kg of NAC (group III) resulted in significant reduction of motor dysfunction (Score=3.1+/-1.3, p=0.002). Application of hypothermia alone (group IV) showed significant recovery of motor functions (Score=3.0+/-1.1, p=0.002), and combination of hypothermia and 50 mg/kg of NAC (group V) showed complete recovery of lower limb motor function (Score=4, p=0.001). Histologic examination of the spinal cord in rabbits with paraplegia revealed several injured neurons. The cords of animals with no motor function deficits showed only minimal cellular infiltrates in the gray matter, and there was good preservation of nerve cells. NAC showed protective effects of the spinal cord. Moderate hypothermia alone also showed protective effects. Combined use of NAC and hypothermia resulted in highly significant recovery of spinal cord function.

Unlabelled: In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia., Implications: Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.