Raman Fiber Photometry for Understanding Mitochondrial Superoxide Burst and Extracellular Calcium Ion Influx upon Acute Hypoxia in the Brain of Freely Moving Animals

2021 ◽  
Author(s):  
Zhichao Liu ◽  
Zhonghui Zhang ◽  
Yuandong Liu ◽  
Yuxiao Mei ◽  
Enduo Feng ◽  
...  
Keyword(s):  
Calcium Ion ◽  
Acute Hypoxia ◽  
Extracellular Calcium ◽  
Mitochondrial Superoxide ◽  
Ion Influx ◽  
Freely Moving ◽  
The Brain

Vasomotor responses in MnSOD-deficient mice

2004 ◽  
Vol 287 (3) ◽  
pp. H1141-H1148 ◽  
Author(s):  
Jon J. Andresen ◽  
Frank M. Faraci ◽  
Donald D. Heistad
Keyword(s):  
Oxidative Stress ◽  
Acute Hypoxia ◽  
Vasomotor Response ◽  
Wild Type ◽  
Similar Extent ◽  
Sod Activity ◽  
Vasomotor Function ◽  
Mitochondrial Superoxide ◽  
Prostaglandin F ◽  
Deficient Mice

MnSOD is the only mammalian isoform of SOD that is necessary for life. MnSOD−/− mice die soon after birth, and MnSOD+/− mice are more susceptible to oxidative stress than wild-type (WT) mice. In this study, we examined vasomotor function responses in aortas of MnSOD+/− mice under normal conditions and during oxidative stress. Under normal conditions, contractions to serotonin (5-HT) and prostaglandin F2α (PGF2α), relaxation to ACh, and superoxide levels were similar in aortas of WT and MnSOD+/− mice. The mitochondrial inhibitor antimycin A reduced contraction to PGF2α and impaired relaxation to ACh to a similar extent in aortas of WT and MnSOD+/− mice. The Cu/ZnSOD and extracellular SOD inhibitor diethyldithiocarbamate (DDC) paradoxically enhanced contraction to 5-HT and superoxide more in aortas of WT mice than in MnSOD+/− mice. DDC impaired relaxation to ACh and reduced total SOD activity similarly in aortas of both genotypes. Tiron, a scavenger of superoxide, normalized contraction to 5-HT, relaxation to ACh, and superoxide levels in DDC-treated aortas of WT and MnSOD+/− mice. Hypoxia, which reportedly increases superoxide, reduced contractions to 5-HT and PGF2α similarly in aortas of WT and MnSOD+/− mice. The vasomotor response to acute hypoxia was similar in both genotypes. In summary, under normal conditions and during acute oxidative stress, vasomotor function is similar in WT and MnSOD+/− mice. We speculate that decreased mitochondrial superoxide production may preserve nitric oxide bioavailability during oxidative stress.

Evaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheres

2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov
Keyword(s):  
Acute Hypoxia ◽  
Life Time ◽  
The Body ◽  
Cerebral Hemispheres ◽  
Antihypoxic Activity ◽  
Hypoxic Episode ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Outbred Mice ◽  
The Brain

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.

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 Simultaneous CMOS-Based Imaging of Calcium Signaling of the Central Amygdala and the Dorsal Raphe Nucleus During Nociception in Freely Moving Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Romeo Rebusi ◽  
Joshua Phillipe Olorocisimo ◽  
Jeric Briones ◽  
Yasumi Ohta ◽  
Makito Haruta ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Central Amygdala ◽  
Critical Areas ◽  
Freely Moving ◽  
Increased Activity ◽  
The Brain ◽  
Dorsal Raphé

Fluorescence imaging devices have been indispensable in elucidating the workings of the brain in living animals, including unrestrained, active ones. Various devices are available, each with their own strengths and weaknesses in terms of many factors. We have developed CMOS-based needle-type imaging devices that are small and lightweight enough to be doubly implanted in freely moving mice. The design also allowed angled implantations to avoid critical areas. We demonstrated the utility of the devices by using them on GCaMP6 mice in a formalin test experiment. Simultaneous implantations to the capsular-lateral central amygdala (CeLC) and dorsal raphe nucleus (DRN) were proven to be safe and did not hinder the execution of the study. Analysis of the collected calcium signaling data, supported by behavior data, showed increased activity in both regions as a result of pain stimulation. Thus, we have successfully demonstrated the various advantages of the device in its application in the pain experiment.

scholarly journals NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording

2018 ◽  
Author(s):  
Marc D. Ferro ◽  
Christopher M. Proctor ◽  
Alexander Gonzalez ◽  
Eric Zhao ◽  
Andrea Slezia ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Signal Amplitude ◽  
Brain Machine Interface ◽  
Behavioral Experiments ◽  
Adult Rats ◽  
Integrative Level ◽  
Machine Interface ◽  
Freely Moving ◽  
The Brain

AbstractMinimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.In this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10µm wide, 1.5µm thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35µm microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology rigs and with measurements of interests in behavioral experiments in adult rats freely moving into maze. We demonstrated that NeuroRoots electrodes reliably detected action potentials for at least 7 weeks and the signal amplitude and shape remained relatively constant during long-term implantation.This research represents a step forward in the direction of developing the next generation of seamless brain-machine interface to study and modulate the activities of specific sub-populations of neurons, and to develop therapies for a plethora of neurological diseases.

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