Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis
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University of Toledo Health Science Campus / OhioLINK
2011
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=mco1313737400 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-mco13137374002021-08-03T05:38:54Z Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis Dwyer, Trisha A. Biomedical Research Neurosciences Ischemia Hypoxia Hypoglycemia Seizures Glyceraldehyde 3-phosphate dehydrogenase GABA receptor Glycolysis Ketogenic diet 2-deoxyglucose Pentose phosphate pathway <p>Brain ischemia induces a metabolic insult that disrupts normal neuronal transmission and leads to a prolonged hyperexcitable state. As a result of increased hyperexcitability, the brain may fire hypersychronous electrical discharges known as seizures. Seizures which become self-sustaining for 30 min or more, called status epilepticus (SE) are highly indicative of a poor prognosis. Thus, identifying how low oxygen and/or low glucose contribute to the generation of seizures may unveil mechanisms related to epileptogenesis, as well as provide a therapeutic target. Often, an imbalance in excitatory and inhibitory neurotransmission is associated with seizure development, which primarily involves glutamate and γ-aminobutyric acid (GABA) neurotransmission, respectively. GABARs are known for mediating the majority of fast inhibitory neurotransmission in the brain and play an integral role in the development of seizures. While GABARs are well-known for mediating anticonvulsant effects, their dysfunction during the development of seizures remains unclear. The lack of oxygen and/or low glucose may alter inhibition in the brain leading to an increased hyperexcitable state. In this thesis, we created a model of mild-to-moderate hypoxia/hypoglycemia that would allowinvestigation into the differential effects of hypoxia, hypoglycemia, or the combination on GABARs in the in vivo setting.</p><p>We found that seizures were readily induced in rats when moderate doses of insulin were combined with or without oxygen. Rats treated with insulin alone (5U/kg) exhibited lethargy and developed myoclonic jerks, barrel rotations, and tonic-clonic seizures. No seizure activity was observed in rats treated with hypoxia (10% FiO2). Pulse oximetry data showed that rats treated with insulin had a decreased heart rate, while hypoxia and hypoxia/hypoglycemia treated rats displayed a decrease in peripheral oxygen saturation (SPO2). Future studies will be directed at assessing the differential effects of low oxygen and/or low glucose on GABARs, with a particular focus on the glycolysis-dependent modulation of GABAAR α1 subunit. A low energy state may disrupt the phosphorylation status of the α1 subunit, which could lead GABAR dysfunction and subsequent hyperexcitability. Although this mechanism bridges glycolysis with neuronal inhibition, whether glycolysis or particular glycolytic enzymes are absolutely necessary in maintaining normal neuronal excitability remains to be established.</p> 2011-12-28 English text University of Toledo Health Science Campus / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=mco1313737400 http://rave.ohiolink.edu/etdc/view?acc_num=mco1313737400 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Research Neurosciences Ischemia Hypoxia Hypoglycemia Seizures Glyceraldehyde 3-phosphate dehydrogenase GABA receptor Glycolysis Ketogenic diet 2-deoxyglucose Pentose phosphate pathway |
| spellingShingle |
Biomedical Research Neurosciences Ischemia Hypoxia Hypoglycemia Seizures Glyceraldehyde 3-phosphate dehydrogenase GABA receptor Glycolysis Ketogenic diet 2-deoxyglucose Pentose phosphate pathway Dwyer, Trisha A. Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis |
| author |
Dwyer, Trisha A. |
| author_facet |
Dwyer, Trisha A. |
| author_sort |
Dwyer, Trisha A. |
| title |
Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis |
| title_short |
Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis |
| title_full |
Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis |
| title_fullStr |
Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis |
| title_full_unstemmed |
Brain Hypometabolism and Seizures: The Dynamics of Hypoxia and Hypoglycemia in Brain Energy Homeostasis |
| title_sort |
brain hypometabolism and seizures: the dynamics of hypoxia and hypoglycemia in brain energy homeostasis |
| publisher |
University of Toledo Health Science Campus / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=mco1313737400 |
| work_keys_str_mv |
AT dwyertrishaa brainhypometabolismandseizuresthedynamicsofhypoxiaandhypoglycemiainbrainenergyhomeostasis |
| _version_ |
1719423003829207040 |