Tetrahydrocurcumin Provides Neuroprotection in Experimental Traumatic Brain Injury and the Nrf2 Signaling Pathway as a Potential Mechanism

Guan, Wei; Chen, Bingji; Lin, Qingjiang; Li, Yasong; Luo, Liangqin; He, Hefan; Fu, Haidong

doi:10.1159/000487998

Cited by 21 publications

(8 citation statements)

References 24 publications

(25 reference statements)

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“…Increased use of marijuana among Americans is coincided with its implication in emergency departments visits, motor vehicle collisions, and trauma [ 15 , 16 ]. THC has been associated with neuroprotective effects after TBI in several preclinical studies [ 17 , 18 ]. A 3-year retrospective review from a Level 1 trauma center by Nguyen et al found that positive THC screens were associated with improved survival after TBI [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

The effects of alcohol and marijuana on survival after severe traumatic brain injury: A retrospective cohort study

Leskovan

Patel

Pederson

et al. 2020

Annals of Medicine and Surgery

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Background Alcohol (ETOH) and marijuana (THC) use have previously shown to improve outcomes after Traumatic Brain Injury (TBI). However, whether TBI severity impacts outcomes among patients tested positive for both ETOH and THC remains unclear. Materials and methods A retrospective review from the Northern Ohio Regional Trauma Registry, which includes deidentified data from six regional hospitals, including three Level 1 and three Level 3 trauma centers, was performed to assess adult (>18 years) patients with severe TBI (head Abbreviated Injury Score ≥ 3) between January 2012 and December 2018 having an alcohol and drug toxicology screen and data regarding outcome at discharge. Patients were divided into two groups: 1) patients with a negative ETOH and drug test, and 2) patients positive for ETOH + THC. Mortality at discharge was the primary outcome measure and multiple logistic regression was used to assess predictors of mortality at discharge. Results A total of 854 (median age: 51 years [range: 18–72]; 34.4% female [294/854]) patients were included. On multiple logistic regression, age (p = 0.003), days in intensive care unit (ICU) (p < 0.001), Glasgow Coma Scale (GCS) (p < 0.001), Injury Severity Score (ISS) (p < 0.001), length of stay (LOS) (p < 0.001), and days on ventilator support (p = 0.032) were significant predictors of mortality at discharge. Blood alcohol content (BAC), cause of TBI, drug class, and sex were not significant predictors of mortality at discharge. Conclusions After severe TBI, positive THC and BAC screening did not predict mortality at discharge after controlling for confounding variables, indicating no survival benefit for patients with severe TBI.

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Section: Discussionmentioning

confidence: 99%

The effects of alcohol and marijuana on survival after severe traumatic brain injury: A retrospective cohort study

Leskovan

Patel

Pederson

et al. 2020

Annals of Medicine and Surgery

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“…Most importantly, the combinational use of curcumin and candesartan, an angiotensin II receptor blocker used for the treatment of hypertension, showed better antioxidative, antiapoptotic, and anti-inflammatory effects than curcumin or candesartan alone [ 89 ]. In addition, tetrahydrocurcumin, the metabolite of curcumin, could also alleviate brain edema and reduce neuronal cell apoptosis, as well as improve neurobehavioral function via the Nrf2 signaling pathway in weight drop-induced TBI mice [ 90 ]. Taken together, curcumin together with its metabolites are useful for the treatment of TBI.…”

Section: The Potential Therapy Of Phytochemicals As Nrf2 Activators I...mentioning

confidence: 99%

Targeting Nrf2-Mediated Oxidative Stress Response in Traumatic Brain Injury: Therapeutic Perspectives of Phytochemicals

Yong

Pan

et al. 2022

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI), known as mechanical damage to the brain, impairs the normal function of the brain seriously. Its clinical symptoms manifest as behavioral impairment, cognitive decline, communication difficulties, etc. The pathophysiological mechanisms of TBI are complex and involve inflammatory response, oxidative stress, mitochondrial dysfunction, blood-brain barrier (BBB) disruption, and so on. Among them, oxidative stress, one of the important mechanisms, occurs at the beginning and accompanies the whole process of TBI. Most importantly, excessive oxidative stress causes BBB disruption and brings injury to lipids, proteins, and DNA, leading to the generation of lipid peroxidation, damage of nuclear and mitochondrial DNA, neuronal apoptosis, and neuroinflammatory response. Transcription factor NF-E2 related factor 2 (Nrf2), a basic leucine zipper protein, plays an important role in the regulation of antioxidant proteins, such as oxygenase-1(HO-1), NAD(P)H Quinone Dehydrogenase 1 (NQO1), and glutathione peroxidase (GPx), to protect against oxidative stress, neuroinflammation, and neuronal apoptosis. Recently, emerging evidence indicated the knockout (KO) of Nrf2 aggravates the pathology of TBI, while the treatment of Nrf2 activators inhibits neuronal apoptosis and neuroinflammatory responses via reducing oxidative damage. Phytochemicals from fruits, vegetables, grains, and other medical herbs have been demonstrated to activate the Nrf2 signaling pathway and exert neuroprotective effects in TBI. In this review, we emphasized the contributive role of oxidative stress in the pathology of TBI and the protective mechanism of the Nrf2-mediated oxidative stress response for the treatment of TBI. In addition, we summarized the research advances of phytochemicals, including polyphenols, terpenoids, natural pigments, and otherwise, in the activation of Nrf2 signaling and their potential therapies for TBI. Although there is still limited clinical application evidence for these natural Nrf2 activators, we believe that the combinational use of phytochemicals such as Nrf2 activators with gene and stem cell therapy will be a promising therapeutic strategy for TBI in the future.

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“…H 2 treatment improved BBB integrity, brain edema, and neurological performance in rats [ 201 - 204 ]. Other natural compounds and their effects are reported in Table 2 [ 205 - 231 ].…”

Section: Novel Pharmacologic Strategies For Tbi: From Experimental To...mentioning

confidence: 99%

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

Battaglini

Siwicka-Gieroba

Rocco

et al. 2021

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: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

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Tetrahydrocurcumin Provides Neuroprotection in Experimental Traumatic Brain Injury and the Nrf2 Signaling Pathway as a Potential Mechanism

Cited by 21 publications

References 24 publications

The effects of alcohol and marijuana on survival after severe traumatic brain injury: A retrospective cohort study

The effects of alcohol and marijuana on survival after severe traumatic brain injury: A retrospective cohort study

Targeting Nrf2-Mediated Oxidative Stress Response in Traumatic Brain Injury: Therapeutic Perspectives of Phytochemicals

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

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