scholarly journals Nutritional Supplementation Reduces Lesion Size and Neuroinflammation in a Sex-Dependent Manner in a Mouse Model of Perinatal Hypoxic-Ischemic Brain Injury

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 176
Author(s):  
Myrna J. V. Brandt ◽  
Cora H. Nijboer ◽  
Isabell Nessel ◽  
Tatenda R. Mutshiya ◽  
Adina T. Michael-Titus ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Brain Injury ◽  
Mouse Model ◽  
Vitamin B12 ◽  
Lesion Size ◽  
Nutritional Supplementation ◽  
Cognitive Outcome ◽  
Dependent Manner ◽  
Experimental Diet

Perinatal hypoxia-ischemia (HI) is a major cause of neonatal brain injury, leading to long-term neurological impairments. Medical nutrition can be rapidly implemented in the clinic, making it a viable intervention to improve neurodevelopment after injury. The omega-3 (n-3) fatty acids docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), uridine monophosphate (UMP) and choline have previously been shown in rodents to synergistically enhance brain phospholipids, synaptic components and cognitive performance. The objective of this study was to test the efficacy of an experimental diet containing DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 in a mouse model of perinatal HI. Male and female C57Bl/6 mice received the experimental diet or an isocaloric control diet from birth. Hypoxic ischemic encephalopathy was induced on postnatal day 9 by ligation of the right common carotid artery and systemic hypoxia. To assess the effects of the experimental diet on long-term motor and cognitive outcome, mice were subjected to a behavioral test battery. Lesion size, neuroinflammation, brain fatty acids and phospholipids were analyzed at 15 weeks after HI. The experimental diet reduced lesion size and neuroinflammation specifically in males. In both sexes, brain n-3 fatty acids were increased after receiving the experimental diet. The experimental diet also improved novel object recognition, but no significant effects on motor performance were observed. Current data indicates that early life nutritional supplementation with a combination of DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 may provide neuroprotection after perinatal HI.

scholarly journals Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Min Jae Kim ◽  
Seo-Yeon Lee ◽  
Ji Young Hwang ◽  
Hyunha Kim ◽  
Ki-Tae Ha ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Mouse Model ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Immunohistochemical Analysis ◽  
Medicinal Herbs ◽  
Neurological Deficits ◽  
Dependent Manner

Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4) was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB) breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg), while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1) expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

306 GCS Does Not Predict Cognitive Outcome 30 Years After Severe Traumatic Brain Injury

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 264-265
Author(s):  
Molly E Hubbard ◽  
Abdullah Bin Zahid ◽  
Gabrielle Meyer ◽  
Kathleen Vonderhaar ◽  
David Y Balser ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Assessment Tool ◽  
Cognitive Status ◽  
Cognitive Outcomes ◽  
Cognitive Outcome ◽  
Symptom Severity Score ◽  
History Of ◽  
Severe Tbi

Abstract INTRODUCTION Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US. The effects of TBI on quality of life may not become apparent for years after the injury. There are conflicting reports in the literature regarding long term outcomes. Physicians are often asked to predict long term functional and cognitive outcomes, with limited data available. METHODS Patients with severe TBI (GCS = 9) who previously participated in a clinical trial during the 1980s were followed up with and compared to healthy controls without history of TBI. A health questionnaire, sports concussion assessment tool version 3 (SCAT3) and the Telephone Interview for Cognitive Status-modified (TICS-m) were completed over the phone and compared with controls using t-test. GCS at admission and 12-month GRS were used to predict to TICS-M at 30 years using linear regression. RESULTS >45 of the initial 168 subjects were confirmed alive, and 37 (13 females; mean age: 52.43 years S.D. 10.7) consented. Controls (n = 58; 23 females; mean age = 54 years, S.D. 11.5) had lower symptom severity score (6.7 S.D. 12.6 versus 20.6 S.D. 25.3; P = 0.005), lower total number of symptoms (3.4 S.D. 4.7 versus 7.12 S.D. 6.5; P = 0.006), higher standardized assessment of concussion score (25.6 S.D. 2.8 versus 21.2 S.D. 6.9; P = 0.001), and lower corrected MPAI-4 (22.3 S.D. 17.0 versus 43.7 S.D. 12.8; P < 0.001). GCS at admission did not predict cognitive status at 30-years assessed using TICS-M (P = 0.345). The Glasgow Outcome Scale score at 12-months was correlated to TICS-M at 30 years (R = 0.548, P < 0.001); each point decrease in GOS decreasing the score at TICS-M by 5.6 points. CONCLUSION Remote history of TBI disrupts the lives of survivors long after injury. Admission GCS does not predict cognitive status 30 years after TBI. The GOS at 12-months predicted the cognitive status assessed using TICS-M score at 30 years.

scholarly journals Genetic or Enzymatic Disruption of Aromatase Inhibits the Growth of Ectopic Uterine Tissue

2002 ◽  
Vol 87 (7) ◽  
pp. 3460-3466 ◽  
Author(s):  
Zongjuan Fang ◽  
Sijun Yang ◽  
Bilgin Gurates ◽  
Mitsutoshi Tamura ◽  
Evan Simpson ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Mouse Model ◽  
Lesion Size ◽  
Dependent Manner ◽  
Wild Type ◽  
Uterine Tissue ◽  
Abdominal Organs ◽  
Letrozole Treatment ◽  
Key Enzyme ◽  
Dose Dependent

Aromatase P450 (P450arom) is the key enzyme for the biosynthesis of estrogen that is essential for the growth of human endometriosis, a pathology characterized by endometrium-like tissue on the peritoneal surfaces of abdominal organs manifest by pelvic pain and infertility. Surgically transplanted autologous uterine tissue to ectopic sites on the peritoneum in mice has been used as an animal model to study endometriosis. Using this mouse model, we evaluated the roles of the P450arom gene and aromatase enzyme activity in the growth of endometriosis represented by ectopic uterine tissues in mice. Endometriosis was induced surgically in the following groups of mice: 1) untreated transgenic mice with disrupted P450arom gene (ArKO); 2) ArKO mice treated with systemic estrogen; 3) untreated wild-type (WT) mice; 4) WT mice treated with estrogen; 5) WT mice treated with the aromatase inhibitor, letrozole; and 6) WT mice treated with letrozole and estrogen. Each group contained eight mice; +/+ littermates of ArKO mice were used as WT controls. Treatment with estrogen increased the size of ectopic uterine tissues in ArKO and WT mice significantly. The ectopic uterine lesions in untreated and estrogen-treated ArKO mice were strikingly smaller than those in untreated and estrogen-treated WT controls, respectively. Systemic treatment of WT mice with letrozole significantly decreased the lesion size in a dose-dependent manner. The addition of estrogen to letrozole treatment increased the ectopic lesion size, although these lesions were significantly smaller than those in mice treated with estrogen only. As tissue controls, the effects of these conditions on normally located (eutopic) uterine tissue were evaluated. The effects of disruption of the P450arom gene and treatments with letrozole and estrogen seemed to be more profound on ectopic tissues, suggesting that ectopic tissues might be more sensitive to estrogen for growth. We conclude that both an intact P450arom gene and the presence of aromatase enzyme activity are essential for the growth of ectopic uterine tissue in a mouse model of endometriosis.

scholarly journals Impact of Age at Pediatric Stroke on Long-term Cognitive Outcome

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013207
Author(s):  
Stephanie Abgottspon ◽  
Qendresa Thaqi ◽  
Leonie Steiner ◽  
Nedelina Slavova ◽  
Sebastian Grunt ◽  
...  
Keyword(s):  
Early Childhood ◽  
Ischemic Stroke ◽  
Processing Speed ◽  
Lesion Size ◽  
Cognitive Outcome ◽  
Late Childhood ◽  
Control Group ◽  
Childhood Stroke ◽  
Arterial Ischemic Stroke

Objectives:To investigate the impact of age at pediatric arterial ischemic stroke on long-term cognitive outcome in order to identify patients particularly at risk for the development of cognitive long-term cognitive sequelae.Methods:This cross-sectional study included patients in the chronic phase of stroke (> 2 years after stroke) previously diagnosed with neonatal or childhood arterial ischemic stroke and a control group. Participants with active epilepsy, severe learning difficulties, or behavioral problems hindering the cognitive assessment were excluded. Several cognitive domains, including intelligence, executive functions (working memory, inhibition, and cognitive flexibility), processing speed, memory, letter fluency, and visual-motor skills were assessed with neuropsychological tests. Cognitive long-term outcome was compared across patients after neonatal stroke (stroke between 0 and 28 days of life), early childhood stroke (stroke between 29 days and < 6 years) and late childhood stroke (stroke between ≥ 6 and < 16 years).Results:52 patients after neonatal or childhood arterial ischemic stroke (median age: 15.3 years, IQR = 10.6 – 18.7) and 49 healthy controls (median age: 13.6 years, IQR = 9.8 – 17.2) met the inclusion criteria. Cognitive outcome was significantly worse in the pediatric stroke group compared to the control group. A non-linear effect of age at stroke (irrespective of lesion size and lesion location) was found for cognitive flexibility, processing speed, and verbal learning with early childhood stroke (29 days to < 6 years) showing significantly worse cognitive outcome compared to neonatal or late childhood stroke (p < .05, FDR-corrected).Conclusion:Age at stroke is an important factor for post-stroke recovery and modulates long-term cognitive outcome irrespective of lesion size and lesion location. Children after early childhood stroke are at particular risk for alterations of long-term cognitive functions.

scholarly journals Caffeine intake increases plasma ketones: an acute metabolic study in humans

2017 ◽  
Vol 95 (4) ◽  
pp. 455-458 ◽  
Author(s):  
Camille Vandenberghe ◽  
Valérie St-Pierre ◽  
Alexandre Courchesne-Loyer ◽  
Marie Hennebelle ◽  
Christian-Alexandre Castellano ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Caffeine Intake ◽  
Dependent Manner ◽  
Medium Chain Triglycerides ◽  
Metabolic Study ◽  
Brain Glucose ◽  
Glucose Reduction ◽  
Dose Dependent ◽  
The Brain

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer’s disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

scholarly journals Brain biomarkers and pre-injury cognition are associated with long-term cognitive outcome in children with traumatic brain injury

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Amy A. Wilkinson ◽  
◽  
Maureen Dennis ◽  
Nevena Simic ◽  
Margot J. Taylor ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Outcome

scholarly journals Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Daniela Hoeber ◽  
Marco Sifringer ◽  
Yohan van de Looij ◽  
Josephine Herz ◽  
Stéphane V. Sizonenko ◽  
...  
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Neuronal Plasticity ◽  
Memory Function ◽  
Neurodevelopmental Outcome ◽  
Cognitive Outcome ◽  
Neonatal Brain ◽  
Adult Rats ◽  
Adult Age

Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

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