Intravenous Edaravone plus Therapeutic Hypothermia Offers Limited Neuroprotection in the Hypoxic-Ischaemic Newborn Piglet

Background: Therapeutic hypothermia (TH) is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (EV; 3-methyl-1-phenyl-2-pyrazolin-5-one). Objectives and Methods: This study aimed to compare the neuroprotective effects of edaravone plus therapeutic hypothermia (TH + EV) with those of TH alone after a hypoxic-ischaemic insult in the newborn piglet. Anaesthetized piglets were subjected to 40 min of hypoxia (3–5% inspired oxygen), and cerebral ischaemia was assessed using cerebral blood volume. Body temperature was maintained at 39.0 ± 0.5°C in the normothermia group (NT, n = 8) and at 33.5 ± 0.5°C (24 h after the insult) in the TH (n = 7) and TH + EV (3 mg/kg intravenous every 12 h for 3 days after the insult; n = 6) groups under mechanical ventilation. Results: Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (p = 0.025 vs. NT), and 15.0 (3.9) in the TH + EV group. The histopathological score of the TH + EV group showed no significant improvement compared with that of the other groups. Conclusion: TH + EV had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.

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Intravenous edaravone plus therapeutic hypothermia offers limited neuroprotection in the hypoxic-ischaemic newborn piglet

10.1101/2020.02.25.964288 ◽

2020 ◽

Author(s):

Satoshi (Hamano) Yamato ◽

Shinji Nakamura ◽

Yinmon Htun ◽

Makoto Nakamura ◽

Wataru Jinnai ◽

...

Keyword(s):

Therapeutic Hypothermia ◽

Cerebral Blood Volume ◽

Free Radical Scavenger ◽

Newborn Piglet ◽

Radical Scavenger ◽

Neuroprotective Effects ◽

The Mean ◽

Additional Therapy ◽

Inspired Oxygen ◽

Histopathological Score

AbstractTherapeutic hypothermia is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one). To compare the neuroprotective effects of edaravone plus therapeutic hypothermia with those of therapeutic hypothermia alone after a hypoxic-ischaemic insult in the newborn piglet, anaesthetized piglets were subjected to 40 min of hypoxia (3–5% inspired oxygen) and cerebral ischaemia was assessed by cerebral blood volume. Body temperature was maintained at 38.5 °C in the normothermia group (NT, n = 8) and at 34 °C (24 h after the insult) in the therapeutic hypothermia (TH, n = 7) and therapeutic hypothermia plus edaravone (3 mg intravenous every 12 h for 3 days after the insult; TH+EV, n = 6) groups under mechanical ventilation. Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (p = 0.025 vs. NT) and 15.0 (3.9) in the TH+EV group. The histopathological score of the TH+EV group showed no significant improvement compared with that of the other groups. In conclusion, edaravone plus therapeutic hypothermia had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.

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S109 – N-2 MPG in Groin Flaps Subjected to Vein Occlusion

Otolaryngology ◽

10.1016/j.otohns.2008.05.282 ◽

2008 ◽

Vol 139 (2_suppl) ◽

pp. P113-P114

Author(s):

Benoit J Gosselin ◽

Louise Davies

Keyword(s):

Free Radical ◽

Sham Group ◽

Venous Occlusion ◽

Free Radical Scavenger ◽

Control Group ◽

Radical Scavenger ◽

Flap Survival ◽

Vein Occlusion ◽

Scavenger Activity ◽

The Mean

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.

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Associations between Uric Acid Level and 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with/without Edaravone

Cerebrovascular Diseases ◽

10.1159/000488038 ◽

2018 ◽

Vol 45 (3-4) ◽

pp. 115-123

Author(s):

Masaki Naganuma ◽

Yuichiro Inatomi ◽

Makoto Nakajima ◽

Toshiro Yonehara ◽

Yukio Ando

Keyword(s):

Uric Acid ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Stroke Outcome ◽

Stroke Patients ◽

Treatment Results ◽

Neuroprotective Effects ◽

The Relationship

Background: Uric acid (UA), an antioxidant with neuroprotective effects, favorably affects stroke outcome. However, the effect has not been examined in patients treated with edaravone, a frequently used free radical scavenger. We investigated whether the use of edaravone affected the relationship between UA levels and outcome in acute ischemic stroke. Methods: We retrospectively evaluated 1,114 consecutive ischemic stroke patients with premorbid modified Rankin Scale (mRS) scores <2 admitted within 24 h of onset (mean, 74 years; median UA levels, 333 μmol/L). We divided the patients into 2 groups using the median UA value as a cutoff, a low UA group (≤333 μmol/L; n = 566) and a high UA group (>333 μmol/L; n = 548), and compared their clinical characteristics and favorable outcomes (mRS <2) at 90 days. We investigated the associations between UA levels and 90-day stroke outcome in patients with and without edaravone treatment. Results: The high UA group had a higher proportion of men, hypertension, atrial fibrillation, and cardioembolic stroke than the low UA group. The high UA group also had a higher proportion of patients with mRS <2 at 90 days (61.5 vs. 54.1%, p = 0.013), but the significance was diminished in multivariate analysis (OR 1.30, 95% CI 0.94–1.71). In subgroup analysis, the high UA group without edaravone exhibited a higher proportion of patients with mRS <2 at 90 days than the low UA group (OR 2.87, 95% CI 1.20–7.16). The high UA group with edaravone did not exhibit this difference. Conclusions: In acute ischemic stroke, the favorable association between high UA levels and outcome at 90 days was not evident in patients treated with edaravone.

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Can Brain Health Be Supported by Vitamin D-Based Supplements? A Critical Review

Brain Sciences ◽

10.3390/brainsci10090660 ◽

2020 ◽

Vol 10 (9) ◽

pp. 660

Author(s):

Mahitab Farghali ◽

Sara Ruga ◽

Vera Morsanuto ◽

Francesca Uberti

Keyword(s):

Vitamin D ◽

Cognitive Decline ◽

Oxidative Dna Damage ◽

Neuroprotective Effect ◽

Antioxidant Properties ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Negative Consequences ◽

Neuroprotective Effects ◽

Aging Conditions

This review presents recent knowledge on the neuroprotective effects of vitamin D and their usefulness as oral supplementation when combined with other molecules, such as curcumin. A critical look at the effectiveness of vitamin D in this field is also provided. Vitamin D plays a crucial role in neuroprotection and in the cognitive decline associated with aging, where vitamin D’s levels are related to the levels of several neurotrophic factors. An important role of vitamin D has also been observed in the mechanism of neuroinflammation, which is the basis of several aging conditions, including cognitive decline and neurodegeration; furthermore, the neuroprotective effect of vitamin D in the cognitive decline of aging has recently been reported. For this reason, many food supplements created for humans contain vitamin D alone or combined with other molecules with antioxidant properties. However, recent studies also explored negative consequences of the use at a high dosage of vitamin D. Vitamin D in tissues or brain cells can also modulate calbindin-D28K, parvalbumin, and calretinin, and is involved in immune function, thanks also to the combination with curcumin. Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. In particular, curcumin is a potent immune-regulatory agent and its administration has been reported to attenuate cognitive impairments. These effects could be exploited in the future to control the mechanisms that lead to the brain decay typical of neurodegenerative diseases.

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Neuroprotective effects of edaravone, a free radical scavenger, on the rat hippocampus after pilocarpine-induced status epilepticus

Seizure ◽

10.1016/j.seizure.2008.06.012 ◽

2009 ◽

Vol 18 (1) ◽

pp. 71-75 ◽

Cited By ~ 15

Author(s):

T. Kamida ◽

M. Fujiki ◽

H. Ooba ◽

M. Anan ◽

T. Abe ◽

...

Keyword(s):

Status Epilepticus ◽

Free Radical ◽

Free Radical Scavenger ◽

Rat Hippocampus ◽

Radical Scavenger ◽

Neuroprotective Effects

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Melatoninergic System in Parkinson’s Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3472032 ◽

2016 ◽

Vol 2016 ◽

pp. 1-31 ◽

Cited By ~ 37

Author(s):

Josiel Mileno Mack ◽

Marissa Giovanna Schamne ◽

Tuane Bazanella Sampaio ◽

Renata Aparecida Nedel Pértile ◽

Pedro Augusto Carlos Magno Fernandes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuroprotective Effect ◽

Antioxidant Properties ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Motor Impairments ◽

Nonmotor Symptoms ◽

Neuroprotective Effects ◽

6 Hydroxydopamine

Melatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulates the expression of neurotrophins that are involved in the survival of dopaminergic neurons and reducesα-synuclein aggregation, thus protecting the dopaminergic system against damage. The unbalance of pineal melatonin synthesis can predispose the organism to inflammatory and neurodegenerative diseases such as Parkinson’s disease (PD). The aim of this review is to summarize the knowledge about the potential role of the melatoninergic system in the pathogenesis and treatment of PD. The literature reviewed here indicates that PD is associated with impaired brain expression of melatonin and its receptors MT1and MT2. Exogenous melatonin treatment presented an outstanding neuroprotective effect in animal models of PD induced by different toxins, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat, and maneb. Despite the neuroprotective effects and the improvement of motor impairments, melatonin also presents the potential to improve nonmotor symptoms commonly experienced by PD patients such as sleep and anxiety disorders, depression, and memory dysfunction.

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ACUTE ISCHEMIC STROKE IN WOMEN: EFFICACY OF THE FREE RADICAL SCAVENGER EDARAVONE

Wiadomości Lekarskie ◽

10.36740/wlek202101114 ◽

2021 ◽

Vol 74 (1) ◽

pp. 72-76

Author(s):

Yuriy P. Vdovychenko ◽

Oleg A. Loskutov ◽

Oleksandr A. Halushko ◽

Maryna A. Trishchynska ◽

Dmytro O. Dziuba ◽

...

Keyword(s):

Free Radical ◽

Free Radical Scavenger ◽

Rapid Decrease ◽

Control Group ◽

Radical Scavenger ◽

Four Score ◽

The Mean ◽

Neuronspecific Enolase ◽

A Prospective Study ◽

Positive Results

The aim: To investigate the effectiveness of usage of the free radical scavenger Edaravone in the therapy of women with AIS. Materials and methods: A prospective study was conducted of 48 women with AIS, divided into two groups. Patients in the first group (n = 36) were treated with edaravone 30 mg twice a day intravenously. Neuroprotectors were not used in the control group (n = 12). Clinical-instrumental and neurological examination (Glasgow scale (SCG), FOUR, NIHSS, and neuronspecific enolase (NSE) levels) were performed on all patients. Results: The mean FOUR score in the 1th group increased from 11.04±0.85 to 15.47±0.63 points against 11.39±0.56 to 13.46±1.49 in the control group (p<0.05). The level of NSE in control group patients increased 10-fold (from 9.2 to 96.4 ng/ml, p<0.01). Subsequently, there was a rapid decrease in NSE level in 1th group, and in the control group until 10 days of treatment, the level of NSE did not reach the reference values (p <0.05). Conclusions: The introduction of edaravone in women with AIS results in positive results already in the acute period of the disease. The use of edaravon was significantly effective on the FOUR scale and the dynamics of NSE levels.

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