Abstract TP447: Edaravone Reduces Hyperperfusion-related Neurological Deficits After Direct Bypass in Adult Moyamoya Disease

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Haruto Uchino ◽  
Naoki Nakayama ◽  
Ken Kazumata ◽  
Kiyohiro Houkin

Background and Purpose: Postoperative hyperperfusion-related transient neurological deficits (TNDs) are frequently observed in adult patients with moyamoya disease (MMD) who undergo direct bypass procedures. The present study evaluated the effect of the free radical scavenger edaravone on postoperative hyperperfusion in adult MMD. Methods: This study included 92 hemispheres in 72 adult patients who underwent direct bypass for MMD. Serial measurements of cerebral blood flow were conducted immediately after surgery and on postoperative days 2 and 7. In 40 hemispheres in 36 patients, edaravone (60 mg/day) was administered from the day of surgery until postsurgical day 7. The incidence of postoperative hyperperfusion and associated TNDs were compared with a control group that included 52 hemispheres in 36 patients. Results: Radiological hyperperfusion was observed in 28/40 (70.0%) and 39/52 (75.0%) hemispheres in the edaravone and control groups, respectively (P = 0.30). Hyperperfusion-related TNDs incidences were significantly lower in the edaravone group compared with the control group (12.5% vs. 32.7%, P = 0.024). Multivariate analysis demonstrated that edaravone administration (P = 0.009) and left-sided surgery (P = 0.037) were significantly correlated with hyperperfusion-related TNDs (odds ratios, 0.3 and 4.2, respectively). Conclusions: Perioperative administration of edaravone reduced the incidence of hyperperfusion-related TNDs after direct bypass procedures in adult patients with MMD.

Neurosurgery ◽  
2011 ◽  
Vol 68 (5) ◽  
pp. 1227-1232 ◽  
Author(s):  
Sung-Chul Jin ◽  
Chang Wan Oh ◽  
O-Ki Kwon ◽  
Gyojun Hwang ◽  
Jae Seung Bang ◽  
...  

Abstract BACKGROUND: Postoperative seizure, well-known in association with other pathologies, has been rarely discussed in adult moyamoya disease. OBJECTIVE: We evaluated postoperative seizures in adult patients with moyamoya undergoing revascularization surgery. METHODS: From 2001 to 2007, 43 adult patients with moyamoya disease underwent 53 revascularization surgeries, consisting of direct bypass with or without indirect bypass. Incidence and profile of postoperative seizures were investigated, with evaluation of influencing factors. Multivariable analysis using a generalized estimation equation was performed to determine which factors were related to postoperative seizure. RESULTS: Seizures developed in 10 sides (18.9%) after revascularization for moyamoya disease, including immediate (<24 hours, n = 0), early (1–7 days, n = 5), late (8–30 days, n = 0), and delayed seizures (≥1 month, n = 7). Early and subsequent delayed seizures developed in the same lesions in 2 patients. Seizures developed only in the patients with combined direct and indirect revascularization. Postoperative temporary neurological deficits with imaging abnormalities were significantly related to postoperative nondelayed seizures (P = .02). Delayed seizures were significantly different according to the location of the recipient artery (P = .03), especially with the frontal branches. By multivariable analysis, revascularization using frontal branches trended toward increased incidence of delayed postoperative seizure, with adjusted odds ratio of 13.78 (95% confidence interval, 1.7-114.1). CONCLUSION: In adult patients with moyamoya disease, the incidence of delayed postoperative seizure seems to be higher than that of other pathologies. The delayed, pronounced formation of synangiosis in moyamoya disease may be related to the development of such delayed postoperative seizures, especially when the location of the recipient artery is frontal.


2015 ◽  
pp. 71-78 ◽  
Author(s):  
X. ZENG ◽  
J. WU ◽  
Q. WU ◽  
J. ZHANG

Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. To investigate the antioxidant mechanism of L-malate in the mitochondria, we analyzed the change in gene expression of two malate-aspartate shuttle (MAS)-related carried proteins (AGC, aspartate/glutamate carrier and OMC, oxoglutarate/malate carrier) in the inner mitochondrial membrane, and three antioxidant enzymes (CAT, SOD, and GSH-Px) in the mitochondria. The changes in gene expression of these proteins and enzymes were examined by real-time RT-PCR in the heart and liver of aged rats treated with L-malate. L-malate was orally administered in rats continuously for 30 days using a feeding atraumatic needle. We found that the gene expression of OMC and GSH-Px mRNA in the liver increased by 39 % and 38 %, respectively, in the 0.630 g/kg L-malate treatment group than that in the control group. The expression levels of SOD mRNA in the liver increased by 39 %, 56 %, and 78 % in the 0.105, 0.210, and 0.630 g/kg L-malate treatment groups, respectively. No difference were observed in the expression levels of AGC, OMC, CAT, SOD, and GSH-Px mRNAs in the heart of rats between the L-malate treatment and control groups. These results predicted that L-malate may increase the antioxidant capacity of mitochondria by enhancing the expression of mRNAs involved in the MAS and the antioxidant enzymes.


2019 ◽  
Vol 16 (32) ◽  
pp. 214-227
Author(s):  
Rebeca CAPARICA ◽  
Erica Aparecida ROZISCA ◽  
Julio César MACENA ◽  
Laís de Almeida CAMPOS ◽  
Diana Fortkamp GRIGOLETTO

Melatonin was discovered by Lerner and Coworkers in 1958, and is the main product secreted by the pineal gland. It is a phylogenetically highly conserved molecule and one of the oldest biological signaling mechanisms. It presents several biological functions, among them the most studied is the regulation of the sleep cycle and wakefulness. In addition, melatonin acts as an immunomodulatory, antioxidant molecule and has anticarcinogenic potential. It also participates in the regulation of mood and control of seasonal reproduction. Melatonin is a potent free radical scavenger and several of its metabolites have the ability to remove singlet oxygen, superoxide radicals, hydroperoxides, hydroxyl radicals and radical lipid peroxides. It easily penetrates cell membranes by being soluble in aqueous and organic media, playing a key role in cell biology. Although their activities are interesting for therapy, their low availability, short half-life, and rapid metabolism restrict their use. In this sense, nanotechnology is a tool that has been studied for the elaboration of systems that improve the pharmacokinetic and pharmacodynamic characteristics of melatonin, in order to potentiate its application in biological models. This review summarizes several studies published in recent years that have shown the most numerous biological activities of melatonin and the improvement of their therapeutic potential through nanotechnology.


Author(s):  
Bargale Sushant Sukumar ◽  
Tripathy T B ◽  
Shashirekha H K ◽  
Suhas Kumar Shetty

In Ayurveda, certain herbal formulas are considered to be Rasayana and they are typically taken over periods of time to regenerate both brain and body tissue. Ashwagandha (Withania Somnifera) is used as an adaptogen, antioxidant, immune modulator, free radical scavenger, anti stress, anti arthritic, antispasmodic, anti inflammatory, nervous tonic, nerve soothing and anticancer agent. Ashwagandha (WS) as a nutritional supplement is yet too established. Maximum oxygen uptake (VO2 max) is a gold standard of cardiopulmonary and muscle cell fitness is considered.  The study evaluated the efficacy of Ashwagandha to improve cardiorespiratory endurance (VO2 max) in healthy subjects. They randomized single blind controlled comparative clinical study. 54 health volunteers in each group, study group received Ashwagandha Choorna 12gm with milk (200ml) empty stomach in the morning and the control group only milk (200ml). Maximal capacity of oxygen intake in ml/kg/min (VO2 max) with Rockport fitness walking test of both study and control group were measured before intervention (0th day), after the intervention (60th day) and follow up (90th day). A significant improvement in the VO2 max (F=20.675, P <0.0001) and Hemoglobin (X2=74.150 P <0.0001) in the study group was found. Supplementation of Ashwagandha (Withania Somnifera) with milk improve hemoglobin and VO2 max (maximum aerobic capacity).


Stroke ◽  
2016 ◽  
Vol 47 (7) ◽  
pp. 1930-1932 ◽  
Author(s):  
Haruto Uchino ◽  
Naoki Nakayama ◽  
Ken Kazumata ◽  
Satoshi Kuroda ◽  
Kiyohiro Houkin

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4944-4944
Author(s):  
Jhon A Guerra ◽  
Maribel Torres-Serrant ◽  
Pedro J Santiago

Abstract Abstract 4944 Introduction: The clinical efficacy of doxorubicin is severely limited by its cardiotoxicity. Antioxidants represent the largest class of chemicals examined as potential protective agents and for which there is continuing interest. Dexrazoxane is the current agent used for the control of doxorubicin related cardiotoxicity. However, in large trials the incidence was reduced only by 50% (1). Vitamin E, a known antioxidant and free radical scavenger agent, has been evaluated in the past as a cardio protective drug in animal models receiving doxorubicin but contradictory conclusions regarding this effect have been reported (2, 3). We hypothesized whether Vitamin E has an effect in cardioprotection in rats receiving doxorubicin. Design and Methods: Three groups of 6 Rats each were used for the experiment. Group 1 received doxorubicin 1.5mg/kg intraperitoneally (IP) weekly for 9 weeks for a total cumulative dose of 13.5mg/kg. Group 2 received Vitamin E 100 IU/kg/weekly by IP injection, 48 hours prior to the doxorubicin. Group 3 received 0.5 cc of saline solution 0.9% IP weekly for 9 weeks as control group. Functional parameters including plasmatic nitric oxide (NO) levels and cardiac ejection fraction (EF) were determined on each group at the end of the experiment. Results: Doxorubicin treatment significantly increased plasmatic NO concentration when compared with controls (35.30 ± 5.63 mM vs. 14.72 ± 2.66 mM, n=6, P=0.016); however, in the group of rats receiving Vitamin E prior to doxorubicin, NO did not have a significant decrease (from 35.30 ± 5.63 mM to 31.77± 8.91 mM n=6, P=0.75). Regarding EF, doxorubicin treatment decreased EF significantly when compared with saline controls rats (59 ± 5.61% vs. 77 ± 3.89 %, n=6, P<0.05); however, in the group of rats receiving Vitamin E prior to doxorubicin, EF did not have a significant improvement (from 59 ± 5.61% to 69.17 ± 4.4, n=6, P=0.24). Conclusion: These results suggest that Vitamin E does not prevent or reduce cardiac injury in rats treated with doxorubicin. Different alternatives including other antioxidants could be explored in an attempt to decrease cardiotoxicity produced by doxorubicin and to improve the effect of the standard cardioprotective agent used Dexrazoxane. Further studies are necessary. References: 1. Swain SM. Adult multicenter trials using dexrazoxane to protect against cardiac toxicity. Semin Onco 1998; 25 (4 Suppl 10):43-7 2. Breed JG, Zimmerman AN, Dormans JA, Pinedo HM. Failure of the antioxidant vitamin E to protect against adriamycin-induced cardiotoxicity in the rabbit. Cancer Res 1980; 40:2033-8 3. Myers CE, McGuire W, Young R. Adriamycin: amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep 1976; 60:961-2 Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 131 (5) ◽  
pp. 1501-1507 ◽  
Author(s):  
Kristine Ravina ◽  
Robert C. Rennert ◽  
Ben A. Strickland ◽  
Mark Chien ◽  
Joseph N. Carey ◽  
...  

Moyamoya disease (MMD) is a progressive, idiopathic cerebrovascular occlusive disease. Various revascularization techniques including direct, indirect, and combined microvascular bypasses have been described. This article presents a modified revascularization technique for MMD utilizing a pedicled temporoparietal fascial flap (TPFF) for combined revascularization. This technique combines a large area of coverage for indirect revascularization with the benefits of a direct bypass. The pedicled TPFF also benefits from intact venous drainage to minimize the risk of flap swelling that could result in complications from mass effect.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P113-P114
Author(s):  
Benoit J Gosselin ◽  
Louise Davies

Objectives In a prior communication, we showed that ischemic rat groin flaps exposed to the free radical scavenger N-2 mercaptopropionylglycine (MPG) at the time of arterial and venous occlusion had a higher rate of survival than untreated flaps. In this study, the objective is to test the efficacy and timing of administration of MPG in salvaging rat groin flaps subjected to venous occlusion alone. Methods Randomized controlled trial. Main outcome is mean percentage of flap survival at 7 days. 30 mature Sprague-Dawley rats were randomized to 3 groups based on timing of treatment with MPG: 1- flap raised, no MPG, no venous occlusion (sham group); 2- flap raised, no MPG, 10-hour period of venous occlusion (control group); 3- flap raised, MPG after 10 hours venous occlusion (post-reperfusion group). Results There was no statistical difference noted in mean survival of venous occluded flaps when comparing the control and post-reperfusion groups, after 7 days. Specifically, the mean flap survival in the control group at 7 days was 10.9% (median 0%, range 0–100%). The mean flap survival in the post-reperfusion group was 14.6% (median 0%, range 0–100%). The mean flap survival in the sham group was 90.0% (median 100%, range 0–100%). Conclusions Post-reperfusion MPG administration is not helpful for flaps subjected to venous occlusion alone. The free-radical scavenger activity of MPG is potentiated within the tissues prior to vein occlusion. Potential applications for free flap salvage would need further study.


2017 ◽  
Vol 100 ◽  
pp. 311-315 ◽  
Author(s):  
Yusuke Egashira ◽  
Keita Yamauchi ◽  
Yukiko Enomoto ◽  
Noriyuki Nakayama ◽  
Shinichi Yoshimura ◽  
...  

2017 ◽  
Vol 126 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Eika Hamano ◽  
Hiroharu Kataoka ◽  
Naomi Morita ◽  
Daisuke Maruyama ◽  
Tetsu Satow ◽  
...  

OBJECTIVE Transient neurological symptoms are frequently observed during the early postoperative period after direct bypass surgery for moyamoya disease. Abnormal signal changes in the cerebral cortex can be seen in postoperative MR images. The purpose of this study was to reveal the radiological features of the “cortical hyperintensity belt (CHB) sign” in postoperative FLAIR images and to verify its relationship to transient neurological events (TNEs) and regional cerebral blood flow (rCBF). METHODS A total of 141 hemispheres in 107 consecutive patients with moyamoya disease who had undergone direct bypass surgery were analyzed. In all cases, FLAIR images were obtained during postoperative days (PODs) 1–3 and during the chronic period (3.2 ± 1.13 months after surgery). The CHB sign was defined as an intraparenchymal high-intensity signal within the cortex of the surgically treated hemisphere with no infarction or hemorrhage present. The territory of the middle cerebral artery was divided into anterior and posterior parts, with the extent of the CHB sign in each part scored as 0 for none; 1 for presence in less than half of the part; and 2 for presence in more than half of the part. The sum of these scores provided the CHB score (0–4). TNEs were defined as reversible neurological deficits detected both objectively and subjectively. The rCBF was measured with SPECT using N-isopropyl-p-[123I]iodoamphetamine before surgery and during PODs 1–3. The rCBF increase ratio was calculated by comparing the pre- and postoperative count activity. RESULTS Cortical hyperintensity belt signs were detected in 112 cases (79.4%) and all disappeared during the chronic period. Although all bypass grafts were anastomosed to the anterior part of the middle cerebral artery territory, CHB signs were much more pronounced in the posterior part (p < 0.0001). TNEs were observed in 86 cases (61.0%). Patients with TNEs showed significantly higher CHB scores than those without (2.31 ± 0.13 vs 1.24 ± 0.16, p < 0.0001). The CHB score, on the other hand, showed no relationship with the rCBF increase ratio (p = 0.775). In addition, the rCBF increase ratio did not differ between those patients with TNEs and those without (1.15 ± 0.033 vs 1.16 ± 0.037, p = 0.978). CONCLUSIONS The findings strongly suggest that the presence of the CHB sign during PODs 1–3 can be a predictor of TNEs after bypass surgery for moyamoya disease. On the other hand, presence of this sign appears to have no direct relationship with the postoperative local hyperperfusion phenomenon. Vasogenic edema can be hypothesized as the pathophysiology of the CHB sign, because the sign was transient and never accompanied by infarction in the present series.


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