scholarly journals Immunohistochemical Analysis of the Spinal Cord Ischemia– Effect of Remote Ischemic Preconditioning in a Porcine Model

2018 ◽  
Vol 21 (3) ◽  
pp. 209 ◽  
Author(s):  
Henri Johannes Haapanen ◽  
Johanna Herajärvi ◽  
Hannu-Pekka Honkanen ◽  
Caius Mustonen ◽  
Hannu Tuominen ◽  
...  

Background: In experimental settings, remote ischemic preconditioning (RIPC) has shown a positive effect regarding spinal cord protection after local ischemia. In this study, we conducted spinal cord immunohistochemistry to demonstrate the protective effect of RIPC after 24 hours of the regional ischemia. Methods: Twenty piglets were randomized into an RIPC group (n = 10) and a control group (n = 10). The RIPC group underwent transient left hind limb ischemia before systematic left subclavian artery and segmental artery occlusion at the level of the diaphragm. Twenty-four hours later, the thoracic and lumbar spinal cords were harvested, and the oxidative stress markers were immunohistochemically analysed. Results: A total of 18 animals survived the 4-hour follow up (10 in the RIPC group, 8 in the control group) and 14 animals survived the 24-hour follow up (7 in each group). In the single sections of the spinal cord, the antioxidant pathway activation was seen in the RIPC group, as OGG1 and DJ-1/PARK7 activation was higher (P = .038 and P = .047, respectively). Conclusions: The results indicate that the neuroprotective effect of RIPC on the spinal cord after local ischemic insult remains controversial.

2011 ◽  
Vol 14 (5) ◽  
pp. 317
Author(s):  
Mehmet Ozkokeli ◽  
Mehmet Ugur Es ◽  
Ugur Filizcan ◽  
Murat Ugurlucan ◽  
Ahmet Sasmazel ◽  
...  

<p><b>Background:</b> Surgery for thoracic and thoracoabdominal aortic aneurysms can be complicated by a significant incidence of neurogenic deficits due to spinal cord ischemia. In this study, we investigated whether ischemic preconditioning (IPC) improves neurologic outcome in a rabbit model.</p><p><b>Methods:</b> Forty rabbits underwent infrarenal aortic occlusion. The IPC group (n = 20) had 10 minutes of aortic occlusion to induce spinal cord ischemia, 40 minutes of reperfusion, and 30 minutes of ischemia, whereas the control group (n = 20) had only 30 minutes of ischemia. Tarlov scoring (0, paraplegia; 4, normal) was used to evaluate neurologic functions 7 days later, and spinal cord segments (L4-L6) were stained with hematoxylin and eosin for histologic evaluation.</p><p><b>Results:</b> Complete paraplegia (grade 0) occurred in 15 (75%) of the 20 control animals, whereas in the IPC group, 13 (65%) of 20 animals were completely normal (grade 4) (<i>P</i> < .05).</p><p><b>Conclusion:</b> IPC is beneficial for protecting against neurologic damage after transient aortic occlusion in a rabbit model; however, the protective mechanisms are not clear.</p>


2010 ◽  
Vol 112 (4) ◽  
pp. 881-891 ◽  
Author(s):  
Hai-Long Dong ◽  
Yi Zhang ◽  
Bin-Xiao Su ◽  
Zheng-Hua Zhu ◽  
Qiu-Han Gu ◽  
...  

Background It remains to be established whether spinal cord ischemic tolerance can be induced by limb remote ischemic preconditioning (RIPC), and the mechanisms underlying the neuroprotective effects of RIPC on the spinal cord need to be clarified. Methods Spinal cord ischemia was studied in New Zealand White rabbits. In experiment 1, all rabbits were subjected to 20-min spinal cord ischemia by aortic occlusion. Thirty minutes before ischemia, rabbits were subjected to sham intervention or RIPC achieved by bilateral femoral artery occlusion (10 min ischemia/10 min reperfusion, two cycles). Dimethylthiourea (500 mg/kg, intravenously), a hydroxyl radical scavenger, or vehicle was given 1 h before RIPC. Antioxidant enzyme activity was measured along with spinal cord histology and neurologic function. In experiment 2, rabbits were subjected to spinal cord ischemia, with or without RIPC. In addition, rabbits were pretreated with various doses of hexamethonium. Results RIPC improved neurologic function and reduced histologic damage. This was associated with increased endogenous antioxidant activity. Dimethylthiourea inhibited the protective effects of RIPC. In contrast, there was no effect of hexamethonium on the protective effect of RIPC. Conclusions An initial oxidative stress acts as a trigger to upregulate antioxidant enzyme activity, rather than the neural pathway, and plays an important role in the formation of the tolerance against spinal cord ischemia by limb RIPC.


2020 ◽  
Vol 27 (5) ◽  
pp. 801-804
Author(s):  
Catharina Gronert ◽  
Nikolaos Tsilimparis ◽  
Giuseppe Panuccio ◽  
Ahmed Eleshra ◽  
Fiona Rohlffs ◽  
...  

Purpose: To report a case of chronic intermittent spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) and its successful treatment using hypogastric artery stenting. Case Report: A 79-year-old patient presented in May 2013 with a thoracic aortic aneurysm (TAA) and a contained rupture. He urgently underwent TEVAR that covered 274 mm of descending thoracic aorta without immediate postoperative signs of acute SCI. At 3-month follow-up, he reported repeating incidents of sudden lower extremity weakness leading to a fall with a humerus fracture. A neurological consultation revealed the tentative diagnosis of intermittent SCI caused by TEVAR and initially recommended a conservative approach. During the following year there was no clinical improvement of the symptoms. Computed tomography angiography showed a high-grade stenosis of the right hypogastric artery, which was stented in November 2014 to improve the collateral network of spinal cord perfusion. Following treatment, the patient had no further neurological symptoms; at 32 months after the reintervention, the imaging follow-up documented a patent stent and continued exclusion of the TAA. Conclusion: Intermittent neurological symptoms after TEVAR should be suspected as chronic intermittent SCI. The improvement of collateral networks of the spinal cord by revascularization of the hypogastric artery is a viable treatment option.


2021 ◽  
Vol 10 (10) ◽  
pp. 2213
Author(s):  
Alessia Scatena ◽  
Pasquale Petruzzi ◽  
Filippo Maioli ◽  
Francesca Lucaroni ◽  
Cristina Ambrosone ◽  
...  

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.


2005 ◽  
Vol 103 (1) ◽  
pp. 84-92 ◽  
Author(s):  
Manabu Kakinohana ◽  
Hideki Harada ◽  
Yasunori Mishima ◽  
Tatsuhiko Kano ◽  
Kazuhiro Sugahara

Background Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion. Methods Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia. Results Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group. Conclusions Although the optimal setting for this electrical preconditioning should be determined in future studies, the results suggest that epidural electrical stimulation will be a useful approach to provide spinal protection against ischemia.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.


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