scholarly journals Drug Action on the Metabolic Changes Induced by Acute Hypoxia on Synaptosomes from the Cerebral Cortex

1982 ◽  
Vol 2 (2) ◽  
pp. 229-239 ◽  
Author(s):  
G. Benzi ◽  
E. Arrigoni ◽  
O. Pastoris ◽  
R. F. Villa ◽  
M. Dossena ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Acute Hypoxia ◽  
Hypoxic Condition ◽  
Creatine Phosphate ◽  
Motor Area ◽  
Cortical Motor ◽  
Anesthetic Action ◽  
Surface Freezing ◽  
Cytidine Diphosphate

The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, normoxic, or hypoxic, untreated beagle dogs and of pentobarbital (Nembutal®)- or cytidine diphosphate (CDP)-choline-treated dogs were incubated and analyzed for ATP, ADP, AMP, creatine phosphate, pyruvate, and lactate. The data were compared with data obtained by the surface freezing technique from the whole contralateral cortical area. The in vivo intracarotid perfusion of the drug differentially affected the content of the metabolites and their ratio. This occurred whether the evaluations were performed in the incubated synaptosomal preparations or in whole cerebral tissue, both during normoxia and after hypoxia (15 min; Pao2 = 17–19 mm Hg). Thus intracarotid perfusion of nembutal increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, whereas the effect on the metabolism of the contralateral cortical motor area as a whole was in all cases less than that observed in the synaptosomal fraction. Perfusion with CDP-choline increased synaptosomal phosphorylation after the hypoxic condition, but had no effect in normoxia or on the whole cortical tissue of the motor area. The possibility of obtaining a cerebral sparing action by utilizing molecules devoid of anesthetic action is suggested.

scholarly journals Responses to stimulation of the motor area of the cerebral cortex

1927 ◽  
Vol 102 (716) ◽  
pp. 222-236 ◽  
Keyword(s):  
Cerebral Cortex ◽  
Motor Cortex ◽  
Motor Area ◽  
Motor Innervation ◽  
Triceps Brachii ◽  
Cortical Motor ◽  
Upper Limit ◽  
Extensor Carpi Radialis ◽  
Present Subject ◽  
Stimulation Of

In a previous paper on concurrent mechanical and electrical responses to stimulation of the motor cortex in the monkey (3), we reported the transmission of stimulus rates of 18 to 68 a second. We were unable at that time to carry the enquiry farther owing to lack of means of obtaining higher variable rates of stimulus. Since then we have improvised apparatus giving higher rates and have been able to continue this part of our investigation, using rates up to 290 a second. The object was to determine the upper limit of rate of stimulus which would be transmitted directly to the muscle. We have also been able to collect much information as to the effects of low rates of stimulus, latent periods and the nature of cortical motor innervation as a whole. In the course of the work six further monkeys were used, all small Macacus Rhesus . Of these two had also been used for experiments having no bearing on the present subject and not of a nature to affect our results. The animals were prepared as previously described and the muscles from which records were obtained were M. brachialis anticus , M. flexor profundus digitorum , M. extensor carpi radialis and M. triceps brachii .

scholarly journals High-resolution in vivo imaging of rhesus cerebral cortex with ultrafast portable photoacoustic microscopy

NeuroImage ◽  
2021 ◽  
pp. 118260
Author(s):  
Wei Qin ◽  
Qi Gan ◽  
Lei Yang ◽  
Yongchao Wang ◽  
Weizhi Qi ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
High Resolution ◽  
In Vivo Imaging ◽  
Photoacoustic Microscopy

scholarly journals Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line

2021 ◽  
Vol 11 (4) ◽  
pp. 308
Author(s):  
Valentina Bravatà ◽  
Walter Tinganelli ◽  
Francesco P. Cammarata ◽  
Luigi Minafra ◽  
Marco Calvaruso ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Line ◽  
Acute Hypoxia ◽  
Hypoxic Condition ◽  
Biological Processes ◽  
Microarray Gene Expression ◽  
Hypoxic Conditions ◽  
Gene Expression Analyses ◽  
Shed Light ◽  
New Strategies

In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.

scholarly journals Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Hua Yang ◽  
Mengjie Zhang ◽  
Jiahao Shi ◽  
Yunhe Zhou ◽  
Zhipeng Wan ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mouse Model ◽  
Glutamate Release ◽  
Critical Role ◽  
Conditional Knockout ◽  
Snare Complex ◽  
Extracellular Glutamate ◽  
Glutamate Level

Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness.

Peptide Blocking Self-Polymerization of Extracellular Calcium-Sensing Receptor Attenuates Hypoxia-Induced Pulmonary Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Rui Xiao ◽  
Shengquan Luo ◽  
Ting Zhang ◽  
Yankai Lv ◽  
Tao Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Disulfide Bonds ◽  
Acute Hypoxia ◽  
Extracellular Domain ◽  
Left Ventricular ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Activation of the CaSR (extracellular calcium-sensing receptor) has been recognized as a critical mediator of hypoxia-induced pulmonary hypertension. Preventive targeting of the early initiating phase as well as downstream events after CaSR activation remains unexplored. As a representative of the G protein-coupled receptor family, CaSR polymerizes on cell surface upon stimulation. Immunoblotting together with MAL-PEG technique identified a reactive oxygen species-sensitive CaSR polymerization through its extracellular domain in pulmonary artery smooth muscle cells upon exposure to acute hypoxia. Fluorescence resonance energy transfer screening employing blocking peptides determined that cycteine129/131 residues in the extracellular domain of CaSR formed intermolecular disulfide bonds to promote CaSR polymerization. The monitoring of intracellular Ca 2+ signal highlighted the pivotal role of CaSR polymerization in its activation. In contrast, the blockade of disulfide bonds formation using a peptide decreased both CaSR and hypoxia-induced mitogenic factor expression as well as other hypoxic-related genes in vitro and in vivo and attenuated pulmonary hypertension development in rats. The blocking peptide did not affect systemic arterial oxygenation in vivo but inhibited acute hypoxia-induced pulmonary vasoconstriction. Pharmacokinetic analyses revealed a more efficient lung delivery of peptide by inhaled nebulizer compared to intravenous injection. In addition, the blocking peptide did not affect systemic arterial pressure, body weight, left ventricular function, liver, or kidney function or plasma Ca 2+ level. In conclusion, a peptide blocking CaSR polymerization reduces its hypoxia-induced activation and downstream events leading to pulmonary hypertension and represents an attractive inhaled preventive alternative worthy of further development.

scholarly journals Aerobic and anaerobic metabolism for the zebrafish, Danio rerio, reared under normoxic and hypoxic conditions and exposed to acute hypoxia during development

2010 ◽  
Vol 70 (2) ◽  
pp. 425-434 ◽  
Author(s):  
WR Barrionuevo ◽  
MN Fernandes ◽  
O Rocha
Keyword(s):  
Danio Rerio ◽  
Anaerobic Metabolism ◽  
Developmental Stages ◽  
Acute Hypoxia ◽  
Lactate Concentration ◽  
Growth Delay ◽  
Hypoxic Conditions ◽  
Aerobic And Anaerobic ◽  
Mild Hypoxia

In order to verify the influence of chronic and acute ambient oxygen levels from egg to adult stage of the zebrafish, in vivo oxygen consumption (MO2), critical tensions of oxygen (Pcrit), heart rate (fH) and total body lactate concentration (Lc) were determined for Danio rerio (Hamilton, 1822) raised at 28 °C under normoxic (7.5 mgO2.L-1 or 80 mm.Hg-1) and hypoxic conditions (4.3 mgO2.L-1) and exposed to acute hypoxia during different developmental stages. Our findings confirmed that very early stages do not respond effectively to ambient acute hypoxia. However, after the stage corresponding to the age of 30 days, D. rerio was able to respond to acute hypoxia through effective physiological mechanisms involving aerobic and anaerobic metabolism. Such responses were more efficient for the fishes reared under hypoxia which showed that D. rerio survival capability increased during acclimation to mild hypoxia. Measurements of body mass and length showed that moderate hypoxia did not affect growth significantly until the fish reached the stage of 60 days. Moreover, a growth delay was verified for the hypoxic-reared animals. Also, the D. rerio eggs-to-larvae survival varied from 87.7 to 62.4% in animals reared under normoxia and mild hypoxia, respectively. However, the surviving animals raised under moderated hypoxia showed a better aptitude to regulate aerobic and anaerobic capacities when exposed to acute hypoxia.

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