scholarly journals Brain Metabolic Correlates of Hypoxic-Ischemic Cerebral Necrosis in Mid-Gestational Sheep Fetuses: Significance of Hypotension

1986 ◽  
Vol 6 (4) ◽  
pp. 425-434 ◽  
Author(s):  
Kenneth R. Wagner ◽  
Pauline Ting ◽  
Margaret V. Westfall ◽  
Shun-Ichi Yamaguchi ◽  
John D. Bacher ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Lactic Acid ◽  
Brain Injury ◽  
White Matter ◽  
Energy Charge ◽  
Fetal Brain ◽  
High Concentrations ◽  
Metabolic Basis ◽  
Cerebral Necrosis

Midgestational sheep fetuses exposed to marked hypoxia for 2 h remain brain intact if MABP is maintained above 30 mm Hg. On the other hand, similarly hypoxic fetuses, if they experience reductions in MABP below 30 mm Hg, develop foci of necrosis that predominantly affect hemispheric white matter and neostriatum. Cortex damage is more restricted and is usually associated with more massive underlying white matter damage. The present study examines the brain metabolic basis for the important role of hypotension in brain injury development in marked hypoxia. Sheep fetuses rendered hypoxic by respiring their ewes with 11% oxygen (fetal Pao2 = 8–12 mm Hg) in which MABP was maintained above 30 mm Hg showed increases in brain lactic acid concentrations to 7–13 μmol/g but unaltered energy charge. In contrast, fetuses that sustained MABP reductions below 30 mm Hg showed increases in lactic acid concentrations in vulnerable structures to 16–24 μmol/g accompanied by marked decreases in energy charge. The vulnerable structures also showed reductions in fructose concentrations but a variable behavior of other brain metabolites including phosphocreatine, glycogen, and glucose. Thus, the present findings suggest a relation between hypotension during marked hypoxia, low energy charge, lactic acid accumulation in brain at high concentrations, and fetal brain injury. The ewes of hypoxic hypotensive fetuses received pentobarbital at lower doses than did those of fetuses that maintained blood pressure. This suggests that pentobarbital plays an important role in protecting the fetal brain from asphyxia by extending the hypoxic fetus's ability to maintain blood pressure in addition to reducing its brain metabolism.

scholarly journals Modeling the Encephalopathy of Prematurity in Animals: The Important Role of Translational Research

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Hannah C. Kinney ◽  
Joseph J. Volpe
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Animal Models ◽  
Translational Research ◽  
Developmental Trajectories ◽  
Axonal Injury ◽  
White Matter Lesions ◽  
Human Condition ◽  
Cerebral White Matter

Translational research in preterm brain injury depends upon the delineation of the human neuropathology in order that animal models faithfully reiterate it, thereby ensuring direct relevance to the human condition. The major substrate of human preterm brain injury is the encephalopathy of prematurity that is characterized by gray and white matter lesions reflecting combined acquired insults, altered developmental trajectories, and reparative phenomena. Here we highlight the key features of human preterm brain development and the encephalopathy of prematurity that are critical for modeling in animals. The complete mimicry of the complex human neuropathology is difficult in animal models. Many models focus upon mechanisms related to a specific feature, for example, loss of premyelinating oligodendrocytes in the cerebral white matter. Nevertheless, animal models that simultaneously address oligodendrocyte, neuronal, and axonal injury carry the potential to decipher shared mechanisms and synergistic treatments to ameliorate the global consequences of the encephalopathy of prematurity.

scholarly journals Human Amnion Epithelial Cells Protect against White Matter Brain Injury after Repeated Endotoxin Exposure in the Preterm Ovine Fetus

2017 ◽  
Vol 26 (4) ◽  
pp. 541-553 ◽  
Author(s):  
Tamara Yawno ◽  
Tharani Sabaretnam ◽  
Jingang Li ◽  
Courtney Mcdonald ◽  
Rebecca Lim ◽  
...  
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Epithelial Cells ◽  
Fetal Brain ◽  
Brain Inflammation ◽  
Periventricular White Matter ◽  
Fetal Sheep ◽  
Human Amnion ◽  
Activated Microglia ◽  
Amnion Epithelial Cells

Intrauterine inflammation is a significant cause of injury to the developing fetal brain. Using a preterm fetal sheep model of in utero infection, we asked whether human amnion epithelial cells (hAECs) were able to reduce inflammation-induced fetal brain injury. Surgery was undertaken on pregnant sheep at ~105 days gestation (term is 147 days) for implantation of vascular catheters. Lipopolysaccharide (LPS; 150 ng/kg bolus) or saline was administered IV at 109, 110, and 111 days. Sixty million fluorescent-labeled hAECs were administered at 110, 111, and 112 days gestation via the brachial artery catheter. Brains were collected at 114 days for histological assessment. hAECs were observed within the cortex, white matter, and hippocampus. Compared to control lambs, LPS administration was associated with significant and widespread fetal brain inflammation and injury as evidenced by increased number of activated microglia in the periventricular white matter ( p = 0.02), increased pyknosis, cell degeneration ( p = 0.01), and a nonsignificant trend of fewer oligodendrocytes in the subcortical and periventricular white matter. Administration of hAECs to LPS-treated animals was associated with a significant mitigation in both inflammation and injury as evidenced by fewer activated microglia ( p = 0.03) and pyknotic cells ( p = 0.03), significantly more oligodendrocytes in the subcortical and periventricular white matter ( p = 0.01 and 0.02, respectively), and more myelin basic protein-positive cells within the periventricular white matter ( p = 0.02). hAEC administration to fetal sheep exposed to multiple doses of LPS dampens the resultant fetal inflammatory response and mitigates associated brain injury.

Role of endothelin-1 in age-dependent cerebrovascular hypotensive responses after brain injury

1999 ◽  
Vol 277 (5) ◽  
pp. H1884-H1894 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Blood Pressure ◽  
Brain Injury ◽  
Cerebral Autoregulation ◽  
Regional Cerebral Blood Flow ◽  
Regional Cerebral Blood ◽  
Endothelin 1 ◽  
Arterial Blood ◽  
Age Dependent ◽  
Cerebrovascular Regulation

This study was designed to compare the effect of fluid percussion brain injury (FPI) on the hypotensive cerebrovascular response in newborn and juvenile pigs as a function of time postinsult and to determine the role of endothelin-1 (ET-1) in any age-dependent differences in hypotensive cerebrovascular regulation after injury. Ten minutes of hypotension (10–15 ml blood/kg) decreased mean arterial blood pressure uniformly in both groups (∼45%). In the newborn, hypotensive pial artery dilation (PAD) was blunted within 1 h, remained diminished for at least 72 h, but was resolved within 168 h postinjury (66 ± 4, 69 ± 4, 71 ± 4, and 64 ± 4% inhibition at 1, 4, 8, and 72 h post-FPI). During normotension, regional cerebral blood flow (rCBF) was decreased by FPI, and hypotension further reduced the already decremented rCBF for at least 72 h. Cerebrospinal fluid (CSF) ET-1 was increased from 26 ± 4 to 206 ± 25 pg/ml within 72 h post-FPI, whereas an ET-1 antagonist partially restored impaired hypotensive PAD and altered hypotensive rCBF. In contrast, hypotensive PAD and altered CBF were only inhibited for 4 h post-FPI in the juvenile (56 ± 3 and 34 ± 4% inhibition at 1 and 4 h post-FPI). CSF ET-1 was only increased from 27 ± 4 to 67 ± 9 pg/ml at 4 h, whereas the concentration returned to preinjury value by 8 h post-FPI. ET-1 antagonism similarly partially restored impaired hypotensive PAD and altered hypotensive rCBF. These data show that FPI disturbs cerebral autoregulation during hypotension both to a greater magnitude and for a longer duration in the newborn than in the juvenile. These data suggest that the greater FPI-induced ET-1 release in the newborn could contribute to age-dependent differences in impaired hypotensive cerebral autoregulation after FPI.

scholarly journals Optimizing Cerebral Autoregulation May Decrease Neonatal Regional Hypoxic-Ischemic Brain Injury

2016 ◽  
Vol 39 (1-4) ◽  
pp. 248-256 ◽  
Author(s):  
Jennifer K. Lee ◽  
Andrea Poretti ◽  
Jamie Perin ◽  
Thierry A.G.M. Huisman ◽  
Charlamaine Parkinson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Brain Injury ◽  
White Matter ◽  
Near Infrared ◽  
Birth Asphyxia ◽  
Neurologic Injury ◽  
Ischemic Brain ◽  
Arterial Blood ◽  
Blood Pressures ◽  
The Mean

Background: Therapeutic hypothermia provides incomplete neuroprotection for neonatal hypoxic-ischemic encephalopathy (HIE). We examined whether hemodynamic goals that support autoregulation are associated with decreased brain injury and whether these relationships are affected by birth asphyxia or vary by anatomic region. Methods: Neonates cooled for HIE received near-infrared spectroscopy autoregulation monitoring to identify the mean arterial blood pressure with optimized autoregulatory function (MAPOPT). Blood pressure deviation from MAPOPT was correlated with brain injury on MRI after adjusting for the effects of arterial carbon dioxide, vasopressors, seizures, and birth asphyxia severity. Results: Blood pressure deviation from MAPOPT related to neurologic injury in several regions independent of birth asphyxia severity. Greater duration and deviation of blood pressure below MAPOPT were associated with greater injury in the paracentral gyri and white matter. Blood pressure within MAPOPT related to lesser injury in the white matter, putamen and globus pallidus, and brain stem. Finally, blood pressures that exceeded MAPOPT were associated with reduced injury in the paracentral gyri. Conclusions: Blood pressure deviation from optimal autoregulatory vasoreactivity was associated with MRI markers of brain injury that, in many regions, were independent of the initial birth asphyxia. Targeting hemodynamic ranges to optimize autoregulation has potential as an adjunctive therapy to hypothermia for HIE.

ROLE OF MRI IN THE EVALUATION OF DIFFUSE AXONAL INJURY

2021 ◽  
pp. 60-61
Author(s):  
Sumit Baviskar ◽  
Sneha Mote ◽  
Vishakha Gajre ◽  
Azhar Patwe
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Severe Form ◽  
Cerebral White Matter ◽  
Gradient Echo ◽  
The Brain

INTRODUCTION: Diffuse axonal injury (DAI) is a relatively less common but severe form of traumatic brain injury. It occurs due to shearing forces and is identied as one of the most important causes of morbidity and mortality in patients with traumatic brain injury. MRI is found to be diagnostic when CTndings are normal and there are persistent unexplained neurologic ndings or at subacute and chronic periods. AIM: To evaluate the role of MRI in the diagnosis of diffuse axonal injury. MATERIALAND METHODS: 9 Subjects were identied retrospectively with the diagnosis of DAI on MRI in last 2 years. The 1.5TMRI scans of the patients with DAI included: T1 and T2- weighted imaging, FLAIR imaging and T2*-weighted gradient echo (GRE) imaging. Lesions were identied and compared on all sequences. RESULTS: The lesions were in cerebral white matter location in the cases of mild DAI, whereas in the severe DAI located in basal ganglia, corpus callosum, dorsal part of the brain stem as well as the cerebral white matter. For Haemorrhagic lesions, GRE is the best tool to detect haemorrhagic DAIs. For Non-haemorrhagic lesion, FLAIR and DWI are the best current tool to detect small and non-haemorrhagic parenchymal lesions, displayed as hyperintense lesions.

scholarly journals Manajemen Tekanan Darah Setelah Cedera Sistem Saraf Pusat

2019 ◽  
Vol 8 (2) ◽  
pp. 132-43
Author(s):  
Radian Ahmad Halimi ◽  
Dewi Yulianti Bisri
Keyword(s):  
Blood Pressure ◽  
Brain Injury ◽  
Blood Pressure Reduction ◽  
Quality Data ◽  
Optimal Management ◽  
High Quality Data ◽  
Brain Injured ◽  
Considerable Controversy ◽  
Injured Patients

Hipertensi yang tidak terkontrol sering dijumpai setelah cedera otak. Mekanisme mengenai respon fisiologis dan patologis ini berhubungan dengan respons autoregulasi yang bertujuan untuk mempertahankan aliran darah otak di area yang terkena cedera. Respons hipertensi awal mungkin akan mempercepat/memicu cedera lebih lanjut. Sebaliknya, penurunan tekanan darah secara agresif justru berhubungan dengan kejadian iskemik. Meskipun tekanan darah sudah jelas berperan sebagai modulator dalam cedera otak akut, berbagai penelitian masih menunjukkan kontroversi dan belum ada data-data berkualitas terkait demografis, manajemen optimal terhadap tekanan darah tinggi dam hasil akhir pada pasien yang mengalami cedera otak akut. Deteksi kelainan autoregulasi yang terjadi setelah cedera otak dan kontrol tekanan darah secara hati-hati sangat dibutuhkan dalam manajemen optimal pasien tersebut. Blood Pressure Management After Central Nervous System InjuryAbstractUncontrolled hypertension is often encountered after brain injury. This mechanism related to physiologic and pathologic response are related to autoregulatory responses aimed at preserving the cerebral blood flow in injured areas. The initial hypertensive response may precipitate further injury. Conversely, aggresive blood pressure reduction may be associated with ischemia. Despite the clear role of blood pressure as a modulator of acute brain injury, there is considerable controversy and a lack of high-quality data regarding the demographics, outcomes, and optimal management of high blood pressure in acute brain-injured patients. Recognition of the autoregulatory abnormalities seen after brain injury and careful control of blood pressure are necessary for the optimal management of these patients.

Management of parenchymal haemorrhage

2016 ◽  
Author(s):  
Candice Delcourt ◽  
Craig Anderson
Keyword(s):  
Blood Pressure ◽  
Developing Countries ◽  
Brain Injury ◽  
Prognostic Factor ◽  
Medical Treatment ◽  
High Blood Pressure ◽  
Intracerebral Haemorrhage ◽  
The World

Parenchymal intracerebral haemorrhage (ICH) affects several million people in the world each year, most of whom reside in developing countries. ICH accounts for 10-40% of strokes and is the least treatable form of stroke with a 30-day mortality of 30-55%, with half of these deaths occurring within the first few days of onset. . High blood pressure is both a causal and prognostic factor for ICH, with early control of hypertension being the only medical treatment which may improve recovery and the level of residual functioning. The role of surgery remains controversial. Management is largely supportive and aimed at reducing further brain injury and preventing complications.

Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy

2020 ◽  
pp. 1-6
Author(s):  
H. Go ◽  
Y. Saito ◽  
H. Maeda ◽  
R. Maeda ◽  
K. Yaginuma ◽  
...  
Keyword(s):  
Brain Injury ◽  
Fetal Brain ◽  
Hypoxic Ischemic Encephalopathy ◽  
Serum Cytokine ◽  
Neurological Outcomes ◽  
Control Serum ◽  
Healthy Control ◽  
Ifn Γ ◽  
Ischemic Encephalopathy

BACKGROUND: The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related o cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity. METHODS: Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems). RESULTS: VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group. CONCLUSION: We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE.

scholarly journals An Integrative View of the Role of Lachancea thermotolerans in Wine Technology

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2878
Author(s):  
Javier Vicente ◽  
Eva Navascués ◽  
Fernando Calderón ◽  
Antonio Santos ◽  
Domingo Marquina ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Yeast Species ◽  
Protective Role ◽  
Positive Influence ◽  
Integrative View ◽  
Key Characteristics ◽  
High Concentrations ◽  
Grape Varieties ◽  
Lachancea Thermotolerans

The interest in Lachancea thermotolerans, a yeast species with unusual characteristics, has notably increased in all ecological, evolutionary, and industrial aspects. One of the key characteristics of L. thermotolerans is the production of high quantities of lactic acid compared to other yeast species. Its evolution has mainly been driven by the influence of the environment and domestication, allowing several metabolic traits to arise. The molecular regulation of the fermentative process in L. thermotolerans shows interesting routes that play a complementary or protective role against fermentative stresses. One route that is activated under this condition is involved in the production of lactic acid, presenting a complete system for its production, showing the involvement of several enzymes and transporters. In winemaking, the use of L. thermotolerans is nowadays mostly focused in early–medium-maturity grape varieties, in which over-ripening can produce wines lacking acidity and with high concentrations of ethanol. Recent studies have reported new positive influences on quality apart from lactic acid acidification, such as improvements in color, glutathione production, aroma, malic acid, polysaccharides, or specific enzymatic activities that constitute interesting new criteria for selecting better strains. This positive influence on winemaking has increased the availability of commercial strains during recent years, allowing comparisons among some of those products. Initially, the management of L. thermotolerans was thought to be combined with Saccaharomyces cerevisiae to properly end alcoholic fermentation, but new studies are innovating and reporting combinations with other key enological microorganisms such as Schizosaccharomyces pombe, Oenocous oeni, Lactiplantibacillus plantarum, or other non-Saccharomyces.

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