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Paul F White - One of the best experts on this subject based on the ideXlab platform.
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intrathecal transplantation of bone marrow stromal cells attenuates blood Spinal Cord barrier disruption induced by Spinal Cord ischemia reperfusion injury in rabbits
Journal of Vascular Surgery, 2013Co-Authors: Bo Fang, He Wang, Xuejun Sun, Wenfei Tan, Paul F WhiteAbstract:Objective Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the Spinal Cord. The blood-Spinal Cord barrier is critical to maintain Spinal Cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-Spinal Cord barrier after Spinal Cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-Spinal Cord barrier disruption induced by Spinal Cord ischemia-reperfusion injury. Methods This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal Cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 10 8 in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-Spinal Cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. Results Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits ( P P P P P Conclusions Pre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-Spinal Cord barrier integrity after Spinal Cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating Spinal Cord injury after aortic occlusion.
Bo Fang - One of the best experts on this subject based on the ideXlab platform.
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Intrathecal transplantation of bone marrow stromal cells attenuates blood-Spinal Cord barrier disruption induced by Spinal Cord ischemia-reperfusion injury in rabbits
Society for Vascular Surgery. Published by Elsevier Inc., 2013Co-Authors: Bo Fang, He Wang, Sun Xue-jun, Li Xiao-qian, Ai Chun-yu, Tan Wen-fei, White, Paul F., Ma HongAbstract:ObjectiveIntrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the Spinal Cord. The blood-Spinal Cord barrier is critical to maintain Spinal Cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-Spinal Cord barrier after Spinal Cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-Spinal Cord barrier disruption induced by Spinal Cord ischemia-reperfusion injury.MethodsThis was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal Cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 108 in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-Spinal Cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured.ResultsIntrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits (P < .01) and attenuated EB extravasation at 4 hours (5.41 ± 0.40 vs 7.94 ± 0.36 μg/g; P < .01) and 24 hours (9.03 ± 0.44 vs 15.77 ± 0.89 μg/g; P < .01) after Spinal Cord ischemia-reperfusion injury. In addition, bone marrow stromal cells treatment suppressed Spinal Cord ischemia-reperfusion injury-induced decreases in occludin (P < .01). Finally, bone marrow stromal cells reduced the excessive expression of MMP-9 and TNF-α (P < .01).ConclusionsPre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-Spinal Cord barrier integrity after Spinal Cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating Spinal Cord injury after aortic occlusion.Clinical RelevanceClinical thoracoabdominal aorta surgery may trigger Spinal Cord ischemia-reperfusion injury, resulting in paraplegia as well as bladder, bowel, and sexual dysfunction. Transplantation of bone marrow stromal cells has attracted increasing attention in the field of nervous system protection, but its mechanisms have not been elucidated completely. The blood-Spinal Cord barrier plays a crucial role to maintain normal Spinal Cord function. This study suggested that intrathecal transplantation of bone marrow stromal cells stabilized blood-Spinal Cord barrier integrity through inhibiting the upregulation of matrix metalloproteinase-9 and tumor necrosis factor-α and ameliorated Spinal Cord ischemia-reperfusion injury. This may provide a novel train of thought to enhance the protective effects of bone marrow stromal cells on Spinal Cord injury
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intrathecal transplantation of bone marrow stromal cells attenuates blood Spinal Cord barrier disruption induced by Spinal Cord ischemia reperfusion injury in rabbits
Journal of Vascular Surgery, 2013Co-Authors: Bo Fang, He Wang, Xuejun Sun, Wenfei Tan, Paul F WhiteAbstract:Objective Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the Spinal Cord. The blood-Spinal Cord barrier is critical to maintain Spinal Cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-Spinal Cord barrier after Spinal Cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-Spinal Cord barrier disruption induced by Spinal Cord ischemia-reperfusion injury. Methods This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal Cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 10 8 in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-Spinal Cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. Results Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits ( P P P P P Conclusions Pre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-Spinal Cord barrier integrity after Spinal Cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating Spinal Cord injury after aortic occlusion.
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ischemic preconditioning protects against Spinal Cord ischemia reperfusion injury in rabbits by attenuating blood Spinal Cord barrier disruption
International Journal of Molecular Sciences, 2013Co-Authors: Bo Fang, Xijia Sun, Naren Bao, Xiaoyan RenAbstract:Ischemic preconditioning has been reported to protect against Spinal Cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood Spinal Cord barrier permeability was measured by Evan's Blue extravasation, Spinal Cord edema was evaluated using the wet-dry method, and Spinal Cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-α (TNF-α) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal Cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood Spinal Cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-α mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood Spinal Cord barrier permeability due to Spinal Cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-α expression.
Samira Saadoun - One of the best experts on this subject based on the ideXlab platform.
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Targeted Perfusion Therapy in Spinal Cord Trauma
Neurotherapeutics, 2020Co-Authors: Samira Saadoun, Marios C. PapadopoulosAbstract:We review state-of-the-art monitoring techniques for acute, severe traumatic Spinal Cord injury (TSCI) to facilitate targeted perfusion of the injured Cord rather than applying universal mean arterial pressure targets. Key concepts are discussed such as intraSpinal pressure and Spinal Cord perfusion pressure (SCPP) at the injury site, respectively, analogous to intracranial pressure and cerebral perfusion pressure for traumatic brain injury. The concept of Spinal Cord autoregulation is introduced and quantified using Spinal pressure reactivity index (sPRx), which is analogous to pressure reactivity index for traumatic brain injury. The U-shaped relationship between sPRx and SCPP defines the optimum SCPP as the SCPP that minimizes sPRx (i.e., maximizes autoregulation), and suggests that not only ischemia but also hyperemia at the injury site may be detrimental. The observation that optimum SCPP varies between patients and temporally in each patient supports individualized management. We discuss multimodality monitoring, which revealed strong correlations between SCPP and injury site metabolism (tissue glucose, lactate, pyruvate, glutamate, glycerol), monitored by surface microdialysis. Evidence is presented that the dura is a major, but unappreciated, cause of Spinal Cord compression after TSCI; we thus propose expansion duroplasty as a novel treatment. Monitoring Spinal Cord blood flow at the injury site has revealed novel phenomena, e.g., 3 distinct blood flow patterns, local steal, and diastolic ischemia. We conclude that monitoring from the injured Spinal Cord in the intensive care unit is a safe technique that appears to enable optimized and individualized Spinal Cord perfusion.
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Spinal Cord blood flow in patients with acute Spinal Cord injuries
Journal of Neurotrauma, 2019Co-Authors: Mathew J Gallagher, Argyro Zoumprouli, Marios C. Papadopoulos, Florence R A Hogg, Samira SaadounAbstract:Abstract The effect of traumatic Spinal Cord injury (TSCI) on Spinal Cord blood flow (SCBF) in humans is unknown. Whether intervention to achieve the recommended mean arterial pressure (MAP) guidel...
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expansion duroplasty improves intraSpinal pressure Spinal Cord perfusion pressure and vascular pressure reactivity index in patients with traumatic Spinal Cord injury injured Spinal Cord pressure evaluation study
Journal of Neurotrauma, 2015Co-Authors: Isaac Phang, Samira Saadoun, Argyro Zoumprouli, Melissa C Werndle, Marek Czosnyka, Georgios V Varsos, Marios C. PapadopoulosAbstract:We recently showed that, after traumatic Spinal Cord injury (TSCI), laminectomy does not improve intraSpinal pressure (ISP), Spinal Cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of Spinal Cord decompression (increase in intradural space, cerebroSpinal fluid around the injured Cord) and Spinal Cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured Cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebroSpinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves Spinal Cord radiological and physiological parameters more effectively than laminectomy alone.
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monitoring of Spinal Cord perfusion pressure in acute Spinal Cord injury initial findings of the injured Spinal Cord pressure evaluation study
Critical Care Medicine, 2014Co-Authors: Melissa C Werndle, Samira Saadoun, Isaac Phang, Marek Czosnyka, Georgios V Varsos, Zofia Czosnyka, Peter Smielewski, A Jamous, B A Bell, Argyro ZoumprouliAbstract:Objectives:To develop a technique for continuously monitoring intraSpinal pressure at the injury site (intraSpinal pressure) after traumatic Spinal Cord injury.Design:A pressure probe was placed subdurally at the injury site in 18 patients who had isolated severe traumatic Spinal Cord injury (Americ
Marios C. Papadopoulos - One of the best experts on this subject based on the ideXlab platform.
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Targeted Perfusion Therapy in Spinal Cord Trauma
Neurotherapeutics, 2020Co-Authors: Samira Saadoun, Marios C. PapadopoulosAbstract:We review state-of-the-art monitoring techniques for acute, severe traumatic Spinal Cord injury (TSCI) to facilitate targeted perfusion of the injured Cord rather than applying universal mean arterial pressure targets. Key concepts are discussed such as intraSpinal pressure and Spinal Cord perfusion pressure (SCPP) at the injury site, respectively, analogous to intracranial pressure and cerebral perfusion pressure for traumatic brain injury. The concept of Spinal Cord autoregulation is introduced and quantified using Spinal pressure reactivity index (sPRx), which is analogous to pressure reactivity index for traumatic brain injury. The U-shaped relationship between sPRx and SCPP defines the optimum SCPP as the SCPP that minimizes sPRx (i.e., maximizes autoregulation), and suggests that not only ischemia but also hyperemia at the injury site may be detrimental. The observation that optimum SCPP varies between patients and temporally in each patient supports individualized management. We discuss multimodality monitoring, which revealed strong correlations between SCPP and injury site metabolism (tissue glucose, lactate, pyruvate, glutamate, glycerol), monitored by surface microdialysis. Evidence is presented that the dura is a major, but unappreciated, cause of Spinal Cord compression after TSCI; we thus propose expansion duroplasty as a novel treatment. Monitoring Spinal Cord blood flow at the injury site has revealed novel phenomena, e.g., 3 distinct blood flow patterns, local steal, and diastolic ischemia. We conclude that monitoring from the injured Spinal Cord in the intensive care unit is a safe technique that appears to enable optimized and individualized Spinal Cord perfusion.
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Spinal Cord blood flow in patients with acute Spinal Cord injuries
Journal of Neurotrauma, 2019Co-Authors: Mathew J Gallagher, Argyro Zoumprouli, Marios C. Papadopoulos, Florence R A Hogg, Samira SaadounAbstract:Abstract The effect of traumatic Spinal Cord injury (TSCI) on Spinal Cord blood flow (SCBF) in humans is unknown. Whether intervention to achieve the recommended mean arterial pressure (MAP) guidel...
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expansion duroplasty improves intraSpinal pressure Spinal Cord perfusion pressure and vascular pressure reactivity index in patients with traumatic Spinal Cord injury injured Spinal Cord pressure evaluation study
Journal of Neurotrauma, 2015Co-Authors: Isaac Phang, Samira Saadoun, Argyro Zoumprouli, Melissa C Werndle, Marek Czosnyka, Georgios V Varsos, Marios C. PapadopoulosAbstract:We recently showed that, after traumatic Spinal Cord injury (TSCI), laminectomy does not improve intraSpinal pressure (ISP), Spinal Cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of Spinal Cord decompression (increase in intradural space, cerebroSpinal fluid around the injured Cord) and Spinal Cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured Cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebroSpinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves Spinal Cord radiological and physiological parameters more effectively than laminectomy alone.
Argyro Zoumprouli - One of the best experts on this subject based on the ideXlab platform.
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Spinal Cord blood flow in patients with acute Spinal Cord injuries
Journal of Neurotrauma, 2019Co-Authors: Mathew J Gallagher, Argyro Zoumprouli, Marios C. Papadopoulos, Florence R A Hogg, Samira SaadounAbstract:Abstract The effect of traumatic Spinal Cord injury (TSCI) on Spinal Cord blood flow (SCBF) in humans is unknown. Whether intervention to achieve the recommended mean arterial pressure (MAP) guidel...
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expansion duroplasty improves intraSpinal pressure Spinal Cord perfusion pressure and vascular pressure reactivity index in patients with traumatic Spinal Cord injury injured Spinal Cord pressure evaluation study
Journal of Neurotrauma, 2015Co-Authors: Isaac Phang, Samira Saadoun, Argyro Zoumprouli, Melissa C Werndle, Marek Czosnyka, Georgios V Varsos, Marios C. PapadopoulosAbstract:We recently showed that, after traumatic Spinal Cord injury (TSCI), laminectomy does not improve intraSpinal pressure (ISP), Spinal Cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of Spinal Cord decompression (increase in intradural space, cerebroSpinal fluid around the injured Cord) and Spinal Cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured Cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebroSpinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves Spinal Cord radiological and physiological parameters more effectively than laminectomy alone.
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monitoring of Spinal Cord perfusion pressure in acute Spinal Cord injury initial findings of the injured Spinal Cord pressure evaluation study
Critical Care Medicine, 2014Co-Authors: Melissa C Werndle, Samira Saadoun, Isaac Phang, Marek Czosnyka, Georgios V Varsos, Zofia Czosnyka, Peter Smielewski, A Jamous, B A Bell, Argyro ZoumprouliAbstract:Objectives:To develop a technique for continuously monitoring intraSpinal pressure at the injury site (intraSpinal pressure) after traumatic Spinal Cord injury.Design:A pressure probe was placed subdurally at the injury site in 18 patients who had isolated severe traumatic Spinal Cord injury (Americ
