Due to a multiplicity of causes provoking traumatic brain injury (TBI), TBI is a highly heterogeneous pathology, characterized by high mortality and disability rates. TBI is an acute neurodegenerative event, potentially and unpredictably evolving into sub-chronic and chronic neurodegenerative events, with transient or permanent neurologic, cognitive, and motor deficits, for which no valid standardized therapies are available. A vast body of literature demonstrates that TBI-induced oxidative/nitrosative stress is involved in the development of both acute and chronic neurodegenerative disorders. Cellular defenses against this phenomenon are largely dependent on low molecular weight antioxidants, most of which are consumed with diet or as nutraceutical supplements. A large number of studies have evaluated the efficacy of antioxidant administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. Points of weakness of preclinical studies are represented by the large variability in the TBI model adopted, in the antioxidant tested, in the timing, dosages, and routes of administration used, and in the variety of molecular and/or neurocognitive parameters evaluated. The analysis of the very few clinical studies does not allow strong conclusions to be drawn on the real effectiveness of antioxidant administration to TBI patients. Standardizing TBI models and different experimental conditions, as well as testing the efficacy of administration of a cocktail of antioxidants rather than only one, should be mandatory. According to some promising clinical results, it appears that sports-related concussion is probably the best type of TBI to test the benefits of antioxidant administration.

Antioxidant therapies in traumatic brain injury

Introduction: The aim of our study was to investigate the effects of subclinical brain lesions and cognitive function on gait performance with or without concurrent cognitive task (i.e., dual task) in community-dwelling elderly subjects.

Subjects and Methods: Between 2010 and 2012, magnetic resonance imaging (MRI) scans were performed for 170 non-demented volunteers (82 men and 88 women with a mean age of 67.5 years). The National Hospital Organization Hizen Psychiatric Center Institutional Review Board approved the study. All participants underwent neuropsychological tests (the Mini Mental State Examination [MMSE], Trail Making Test [TMT] and Rivermead Behavioral Memory Test [RBMT]). Time to complete the Timed Up and Go test was measured under two conditions: 1) Timed Up and Go test, and 2) dual task, walking while adding 3 to a predefined number “1”. Impaired gait velocity was defined as the most prolonged quintile in the time of single (>9.0 sec) and dual (>11.0 sec) tasks. We determined indices for atrophy using Voxcel-based Specific Regional Analysis for Alzheimer’s disease (VSRAD). Multivariate analysis was done using the logistic regression analysis with IBM SPSS Statistics 18 software for Windows.

Results: Mean education years was 11.3±2.1 (S.D.) years, and mean MMSE score was 27.8±2.1. Silent brain infarction, deep white matter lesions (DWMLs), periventricular hyperintensities and cerebral microbleeds were detected in 19 (11.2%), 50 (29.4%), 24 (14.1%) and 8 (4.7%), respectively. Impaired gait velocity of single task (Timed Up and Go test) was associated with DWMLs (OR 2.57, 95% CI 1.16-5.69) after adjusted for age, sex, education, MMSE, TMT, RBMT, and MRI findings. Impaired gait velocity of the dual task walking was associated with age (OR 3.59/10 years, 95% CI 1.91-6.73) and score of the RBMT (OR 0.88, 95% CI 0.79-0.99), whereas MRI findings including brain atrophy (VSRAD) were not associated with reduced speed of dual task walking.

Conclusions: Gait disturbance detected by single task was related to DWMLs, while dual task walking revealed an association between reduced gait speed and cognitive dysfunction. The present study showed that gait represents not only physical functioning but also cognitive dysfunction in healthy elderly individuals.

Abstract T P128: Dual Task Walking Reveals Cognitive Dysfunction in Community-Dwelling Elderly Subjects: The Sefuri Brain MRI Study

Traumatic brain injury (TBI) represents one of the major causes of death worldwide and leads to persisting neurological deficits in many of the survivors. One of the most significant long-term sequelae deriving from TBI is neurodegenerative disease, which is a group of incurable diseases that impose a heavy socio-economic burden. However, mechanisms underlying the increased susceptibility of TBI to neurodegenerative disease remain elusive. The neurovascular unit (NVU) is a functional unit composed of neurons, neuroglia, vascular cells, and the basal lamina matrix. The key role of NVU dysfunction in many central nervous system diseases has been revealed. Studies have proved the presence of prolonged structural and functional abnormalities of the NVU after TBI. Moreover, growing evidence suggests impaired NVU function is also implicated in neurodegenerative diseases. Therefore, we propose the Neurovascular Unit Dysfunction (NVUD) Hypothesis, in which the persistent NVU dysfunction is thought to underlie the development of post-TBI neurodegeneration. We deduce NVUD Hypothesis through relational inference and supporting evidence, and suggest continued NVU abnormalities following TBI serve as the pathophysiological substrate and trigger yielding chronic neuroinflammation, proteinopathies and oxidative stress, consequently leading to the progression of neurodegenerative diseases. The NVUD Hypothesis may provide potential treatment and prevention strategies for TBI and late-onset neurodegenerative diseases.

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Persistent Neurovascular Unit Dysfunction: Pathophysiological Substrate and Trigger for Late-Onset Neurodegeneration After Traumatic Brain Injury.

Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. It has a variety of valuable pharmacological and therapeutic activities including antioxidant, anti-inflammatory, anti-diabetic and anti-tumor. These pharmacological impacts have been demonstrated in in vitro and in vivo studies. Also, clinical trials have revealed the efficacy of troxerutin for management of phlebocholosis and hemorrhoidal diseases. In the present review, we focus on the therapeutic effects and biological activities of troxerutin as well as its molecular signaling pathways.

https://koreascience.or.kr:443/article/JAKO202111841186845.pdf

Biological and Therapeutic Effects of Troxerutin: Molecular Signaling Pathways Come into View

Cognitive frailty (CF) is gaining an increasing amount of attention in geriatric research. CF refers to the co-occurrence of physical frailty and cognitive impairment in people without dementia. Neuroimaging of elderly people has revealed the presence of numerous white matter lesions, which is a typical biomarker of cerebral small vessel disease (SVD) on magnetic resonance images. The aim of the present study was to estimate the prevalence of CF in elderly Chinese patients with SVD. One hundred and thirty elderly patients with SVD were recruited for this cross-sectional observational study. Participants who met three to five of the Fried criteria of the physical frailty (PF) phenotype (shrinking, weakness, slowness, self-reported exhaustion, or low physical activity) were classified as having PF. Then, individuals with PF were defined as having CF if mild cognitive impairment was discovered by the Mini-Mental State Examination. Lastly, a series of cognitive function tests and the dual-task walking paradigm were examined. Based on the CF diagnostic criteria, the frequency of CF was 23.08% among elderly Chinese patients with SVD. Furthermore, CF-positive patients had a more significant SVD burden, based on magnetic resonance imaging findings. Logistic regression analysis, which was adjusted for age, sex, education, and comorbidities, showed that CF was negatively correlated with the dual-task walking speed in elderly people with SVD. Thus, SVD burden might be an indicator of CF phenotype. In elderly patients with SVD, CF was associated with dual task walking performance.

/pdf/cognitive-frailty-among-elderly-chinese-patients-with-1tcst60sl6.pdf

Cognitive Frailty Among Elderly Chinese Patients With Cerebral Small Vessel Disease: A Structural MRI Study.

Background: Neurovascular dysfunction caused by traumatic brain injury (TBI) is characterized by cerebralvascular damage, blood–brain barrier (BBB) breakdown, brain edema, etc. This study was desig...

Troxerutin cerebroprotein hydrolysate injection ameliorates neurovascular injury induced by traumatic brain injury - via endothelial nitric oxide synthase pathway regulation.

The term small vessel disease (SVD) encompasses all the pathological processes that affect the small vessels of the brain, including small arteries and arterioles but also capillaries and small veins, which can result in multi-domain cognitive deficits. The digital clock drawing test (dCDT) has been proved to be a more useful assessment tool for cognitive disorders compared to traditional clock drawing test DT (tCDT) in many neuropsychological diseases. This study aimed to check whether this tool worked well in capturing some specific aspects of cognitive performance in aged patients with SVD. A total of 20 aged patients with high-burden SVD (severe-SVD), 10 aged patients with low burden SVD (low-SVD), and 10 age-matched (healthy) individuals were grouped according to Fazekas' score. The dCDT and a series of neuropsychological assessments were performed to evaluate the cognitive function of participants. severe-SVD patients showed higher air-time percentage and lower mean handwriting/drawing pressure on surface during drawing compared with low-SVD and healthy subjects. The linear regression analysis adjusted for age, gender and education showed that the air-time percentage during drawing correlated with the choice reaction test (CRT) and the digit symbol substitution test (DSST), and the mean handwriting/drawing pressure on surface showed a limited correlation with DSST. The data indicated that some early manifestations of cognitive deficits in aged patients with SVD could be detected using the dCDT with a brand-new perspective different from the tCDT.

/pdf/assessing-performance-on-digital-clock-drawing-test-in-aged-4793su1php.pdf

Assessing Performance on Digital Clock Drawing Test in Aged Patients With Cerebral Small Vessel Disease.

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been modified into many versions. With the development of digital technologies, TMT is now modified to a digitized version. The present study demonstrated digital TMT (dTMT) performed on a computer, and Walking TMT (WTMT) on the floor. Both revealed more information compared with the traditional version of TMT.

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test.

Gait characteristics under single-/dual-task walking conditions in elderly patients with cerebral small vessel disease: Analysis of gait variability, gait asymmetry and bilateral coordination of gait.

Hóngyi Zhào

Papers

Troxerutin cerebroprotein hydrolysate injection ameliorates neurovascular injury induced by traumatic brain injury - via endothelial nitric oxide synthase pathway regulation.

Assessing Performance on Digital Clock Drawing Test in Aged Patients With Cerebral Small Vessel Disease.

Cognitive Frailty Among Elderly Chinese Patients With Cerebral Small Vessel Disease: A Structural MRI Study.

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test.

Gait characteristics under single-/dual-task walking conditions in elderly patients with cerebral small vessel disease: Analysis of gait variability, gait asymmetry and bilateral coordination of gait.