scholarly journals Endogenous responses in brain pH and PO2 in a rodent model of birth asphyxia

2019 ◽  
Author(s):  
Alexey S. Pospelov ◽  
Martin Puskarjov ◽  
Kai Kaila ◽  
Juha Voipio
Keyword(s):  
Birth Asphyxia ◽  
Respiratory Acidosis ◽  
Recovery Phase ◽  
Rodent Model ◽  
Brain Maturation ◽  
Maturation Stage ◽  
Systemic Hypoxia ◽  
Brain Ph ◽  
Old Rats ◽  
The Brain

ABSTRACTAimTo study brain-sparing physiological responses in a rodent model of birth asphyxia which reproduces the asphyxia-defining systemic hypoxia and hypercapnia.MethodsSteady or intermittent asphyxia was induced for 15-45 min in anesthetized 6 and 11 days old rats and neonatal guinea pigs using gases containing 5% or 9% O2 plus 20% CO2 (in N2). Hypoxia and hypercapnia were induced with low O2 and high CO2, respectively. Oxygen partial pressure (PO2) and pH were measured with microsensors within the brain and subcutaneous (“body”) tissue. Blood lactate was measured after asphyxia.ResultsBrain and body PO2 fell to apparent zero with little recovery during 5% O2 asphyxia and 5% or 9% O2 hypoxia, and increased more than twofold during 20% CO2 hypercapnia. Unlike body PO2, brain PO2 recovered rapidly to control after a transient fall (rat), or was slightly higher than control (guinea pig) during 9% O2 asphyxia. Asphyxia (5% O2) induced a respiratory acidosis paralleled by a progressive metabolic (lact)acidosis that was much smaller within than outside the brain. Hypoxia (5% O2) produced brain-confined alkalosis. Hypercapnia outlasting asphyxia suppressed pH recovery and prolonged the post-asphyxia PO2 overshoot. All pH changes were accompanied by consistent shifts in the blood-brain barrier potential.ConclusionRegardless of brain maturation stage, hypercapnia can restore brain PO2 and protect the brain against metabolic acidosis despite compromised oxygen availability during asphyxia. This effect extends to recovery phase if normocapnia is restored slowly, and it is absent during hypoxia, demonstrating that exposure to hypoxia does not mimic asphyxia.

scholarly journals Endogenous brain‐sparing responses in brain pH and PO 2 in a rodent model of birth asphyxia

2020 ◽  
Vol 229 (3) ◽  
Author(s):  
Alexey S. Pospelov ◽  
Martin Puskarjov ◽  
Kai Kaila ◽  
Juha Voipio
Keyword(s):  
Birth Asphyxia ◽  
Rodent Model ◽  
Brain Ph

Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

1974 ◽  
Vol 32 ◽  
pp. 148-149
Author(s):  
D. E. Philpott ◽  
A. Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Salivary Gland ◽  
Carotid Artery ◽  
Basement Membrane ◽  
Coronary Vessels ◽  
Ruthenium Red ◽  
E Coli ◽  
Old Rats ◽  
The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

scholarly journals EXTH-71. CYTOSTATIC HYPOTHERMIA FOR GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii102-ii103
Author(s):  
Syed Faaiz Enam ◽  
Jianxi Huang ◽  
Cem Kilic ◽  
Connor Tribble ◽  
Martha Betancur ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Progression Free Survival ◽  
Rodent Model ◽  
Behavioral Alterations ◽  
Free Survival ◽  
Tumor Bearing ◽  
Car T ◽  
The Brain

Abstract As a cancer therapy, hypothermia has been used at sub-zero temperatures to cryosurgically ablate tumors. However, these temperatures can indiscriminately damage both tumorous and healthy cells. Additionally, strategies designed to kill tumor typically accelerate their evolution and recurrence can be inevitable in cancers such as glioblastoma (GBM). To bypass these limitations, here we studied the use of hypothermia as a cytostatic tool against cancer and deployed it against an aggressive rodent model of GBM. To identify the minimal dosage of ‘cytostatic hypothermia’, we cultured at least 4 GBM lines at 4 continuous or intermittent degrees of hypothermia and evaluated their growth rates through a custom imaging-based assay. This revealed cell-specific sensitivities to hypothermia. Subsequently, we examined the effects of cytostatic hypothermia on these cells by a cursory study of their cell-cycle, energy metabolism, and protein synthesis. Next, we investigated the use of cytostatic hypothermia as an adjuvant to chemotherapy and CAR T immunotherapy. Our studies demonstrated that cytostatic hypothermia did not interfere with Temozolomide in vitro and may have been synergistic against at least 1 GBM line. Interestingly, we also demonstrated that CAR T immunotherapy can function under cytostatic hypothermia. To assess the efficacy of hypothermia in vivo, we report the design of an implantable device to focally administer cytostatic hypothermia in an aggressive rodent model of F98 GBM. Cytostatic hypothermia significantly doubled the median survival of tumor-bearing rats with no obvious signs of distress. The absence of gross behavioral alterations is in concurrence with literature suggesting the brain is naturally resilient to focal hypothermia. Based on these findings, we anticipate that focally administered cytostatic hypothermia alone has the potential to delay tumor recurrence or increase progression-free survival in patients. Additionally, it could also provide more time to evaluate concomitant, curative cytotoxic treatments.

Neurodevelopment in the first three years: implications for child development, professional practice and policy

2014 ◽  
Vol 9 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Danya Glaser
Keyword(s):  
Brain Development ◽  
Brain Activity ◽  
Brain Maturation ◽  
Policy And Practice ◽  
Content Type ◽  
Key Issues ◽  
And Function ◽  
The Relationship ◽  
The Brain ◽  
Brain Connections

Purpose – The purpose of this paper is to outline brain structure and development, the relationship between environment and brain development and implications for practice. Design/methodology/approach – The paper is based on a selected review of the literature and clinical experience. Findings – While genetics determine the sequence of brain maturation, the nature of brain development and functioning is determined by the young child's caregiving environment, to which the developing brain constantly adapts. The absence of input during sensitive periods may lead to later reduced functioning. There is an undoubted immediate equivalence between every mind function – emotion, cognition, behaviour and brain activity, although the precise location of this in the brain is only very partially determinable, since brain connections and function are extremely complex. Originality/value – This paper provides an overview of key issues in neurodevelopment relating to the development of young children, and implications for policy and practice.

Brain pH responses to sodium bicarbonate and Carbicarb during systemic acidosis

1989 ◽  
Vol 256 (5) ◽  
pp. H1316-H1321 ◽  
Author(s):  
J. I. Shapiro ◽  
M. Whalen ◽  
R. Kucera ◽  
N. Kindig ◽  
G. Filley ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Ammonium Chloride ◽  
Respiratory Acidosis ◽  
Arterial Pco2 ◽  
Bicarbonate Therapy ◽  
Brain Ph ◽  
Dose Dependent ◽  
Intracellular Alkalinization

Rats subjected to ammonium chloride-induced metabolic acidosis or respiratory acidosis caused by hypercapnia were given alkalinization therapy with either sodium bicarbonate or Carbicarb. Ammonium chloride induced dose-dependent systemic acidosis but did not affect intracellular brain pH. Hypercapnia caused dose-dependent systemic acidosis as well as decreases in intracellular brain pH. Sodium bicarbonate treatment resulted in systemic alkalinization and increases in arterial PCO2 in both acidosis models, but it caused intracellular brain acidification in rats with ammonium chloride acidosis. Carbicarb therapy resulted in systemic alkalinization without major changes in arterial PCO2 and intracellular brain alkalinization in both acidosis models. These data demonstrate that bicarbonate therapy of systemic acidosis may be associated with "paradoxical" intracellular brain acidosis, whereas Carbicarb causes both systemic and intracellular alkalinization under conditions of fixed ventilation.

Spatially Localized Magnetic Resonance Spectroscopy of the Brains of Normal and Asphyxiated Newborns

PEDIATRICS ◽  
1991 ◽  
Vol 87 (3) ◽  
pp. 273-282
Author(s):  
J. Moorcraft ◽  
N. M. Bolas ◽  
N. K. Ives ◽  
P. Sutton ◽  
M. J. Blackledge ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Tissue ◽  
Neurodevelopmental Outcome ◽  
Birth Asphyxia ◽  
Resonance Spectroscopy ◽  
Rotating Frame ◽  
Metabolic Derangement ◽  
Brain Surface ◽  
The Brain

Phase-modulated rotating frame imaging is a modification of magnetic resonance spectroscopy, which uses a linear radiofrequency field gradient to obtain spatially localized biochemical information. Phase-modulated rotating frame imaging was used to study regional cerebral energy metabolism in the brains of 9 normal newborns and 25 newborns after birth asphyxia. Relative concentrations of phosphorus-containing metabolites and intracellular pH were determined for brain tissue at three specified depths below the brain surface for all neonates. Wide variations in metabolite ratios were seen among normal neonates, and considerable metabolic heterogeneity was demonstrated in individual neonates by depth-resolved spectroscopy. Asphyxiated neonates with severe hypoxic-ischemic encephalopathy and a poor neurodevelopmental outcome showed the expected rise in inorganic orthophosphate and fall in phosphocreatine concentrations in both global and spatially localized spectra. Phase-modulated rotating frame imaging showed that metabolic derangement was less in superficial than in deeper brain tissue. The inorganic orthophosphateadenosine triphosphate ratio from 1 to 2 cm below the brain surface was more accurate than any global metabolite ratio for the identification of neonates with a poor short-term outcome. These data are consistent with the known vulnerability of subcortical brain tissue to hypoxic-ischemic injury in the full-term neonate.

DA mediated intermediate-early genes activation in the brain of young and old rats

1997 ◽  
Vol 42 (1) ◽  
pp. 95S-96S
Author(s):  
L. Giardino ◽  
M. Zanni ◽  
M. Pozza ◽  
F. Magliani ◽  
L. Calzà
Keyword(s):  
Early Genes ◽  
Old Rats ◽  
The Brain

Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain

1994 ◽  
Vol 267 (5) ◽  
pp. R1273-R1279 ◽  
Author(s):  
F. Thies ◽  
C. Pillon ◽  
P. Moliere ◽  
M. Lagarde ◽  
J. Lecerf
Keyword(s):  
Fatty Acids ◽  
Rat Brain ◽  
Acid Moiety ◽  
Degree Of Unsaturation ◽  
Old Rats ◽  
Young Rat ◽  
Arachidonic Acids ◽  
The Brain ◽  
Uptake And Metabolism ◽  
Preferential Incorporation

The uptake and metabolism of [3H]docosahexaenoic acid (DHA) esterified at the sn-2 position of lysophosphatidylcholine (lysoPC DHA) and in the unesterified form, both bound to albumin, was studied in 20-day-old rats. LysoPC DHA was preferentially recovered in the brain (4-5% of the injected radioactivity) over the unesterified form of DHA (0.3-0.4%). Conversely, the lysoPC form was taken up less than or at the same extent as the unesterified form by the liver, heart, and kidney. In the brain, DHA was mainly recovered in phosphatidylethanolamine whether the esterified or the unesterified form was used, although DHA from lysoPC was esterified at the same extent in phosphatidylcholine and phosphatidylethanolamine after 2.5 min. The uptake of labeled palmitic, oleic, linoleic, and arachidonic acids, esterified or not in lysophosphatidylcholine, was also studied in brain, liver, heart, and kidney. Only the brain preferentially incorporated unsaturated (but not saturated) lysoPC, with the uptake increasing with the degree of unsaturation of the fatty acid moiety. These results strongly suggest that the young rat brain specifically utilizes albumin-lysoPC-containing polyunsaturated fatty acids.

One-year Retention of Gadolinium in the Brain: Comparison of Gadodiamide and Gadoterate Meglumine in a Rodent Model

Radiology ◽  
2018 ◽  
Vol 288 (2) ◽  
pp. 424-433 ◽  
Author(s):  
Philippe Robert ◽  
Stefanie Fingerhut ◽  
Cécile Factor ◽  
Véronique Vives ◽  
Justine Letien ◽  
...  
Keyword(s):  
Rodent Model ◽  
Gadoterate Meglumine ◽  
One Year ◽  
The Brain

scholarly journals Combined Effects of Radiation and Methotrexate on the Cells of the Rat Subependymal Plate

1983 ◽  
Vol 76 (10) ◽  
pp. 848-852 ◽  
Author(s):  
A D Morris ◽  
J W Hopewell
Keyword(s):  
Cell Types ◽  
Intraventricular Injection ◽  
Nuclear Density ◽  
X Rays ◽  
Subependymal Plate ◽  
Severe Effect ◽  
Old Rats ◽  
Effects Of Radiation ◽  
Log Linear ◽  
The Brain

The brains of 20-week-old rats were locally irradiated with single doses of X-rays (400–1400 cGy). A similar group of animals received an intraventricular injection of methotrexate (MTX) prior to irradiation with single doses of X-rays (600–1400 cGy). Animals were killed six weeks after irradiation. A group of unirradiated age-matched animals acted as controls. In irradiated animals, the most severe effect on the subependymal plate (SEP) of the brain was denoted by the fall in the mitotic count (MC) and the number of small dark (SD) nucleated cells. SD nucleated cells are believed to represent the proliferative compartment of the subependymal layer. Other cell types in the SEP, believed to arise from the SD nucleated population, were affected to a lesser degree. After combination treatment with MTX, the decline in the MC and the SD nuclear density was more severe. The data for the dose-related decline in SD nuclear density and the MC fitted equally well on log-linear and linear plots. From the log-linear plots of the data it was concluded that MTX was radiation dose modifying (DMF 1.25–1.44). However, on the basis of the linear plots the effect of radiation and MTX was apparently additive. While no firm conclusions could be drawn regarding the mechanism of action of MTX on the radiation response of SEP cells, the possible mechanisms are discussed.

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