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You searched for subject:(Neuronal hyperexcitability). Showing records 1 – 3 of 3 total matches.

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University of Houston

1. -9202-6472. Regulating Neuronal Hyperexcitability: The Role of Glutamate Transport, Cannabinoids, and Platinum-Based Anti-Cancer Drugs.

Degree: PhD, Cell and Molecular Biology, 2017, University of Houston

Our studies consist of three distinct projects addressing the modulation of neuronal hyperexcitability states. Hyperexcitability is linked to many neurological disorders and can occur as a consequence of excitatory/inhibitory imbalance, head trauma, or chemical toxin exposure. In this dissertation, each project uses distinct pharmacological approaches in two models of hyperexcitability. The first study focuses on glutamate dysregulation in the hyper-excitable physiological state called cortical spreading depression (CSD). CSD is implicated in several neurological disorders including stroke, migraine aura, epilepsy, and traumatic brain injury (TBI). Despite the critical link between increased glutamate levels during CSD and following TBI, the role of astrocytic glutamate transporters on CSD properties remain unknown. We revealed that impaired glutamate transport and acute injury profoundly affected the physiological and spatiotemporal properties of CSD and neuronal excitability. Our findings emphasize the importance of glutamate transport and brain injury on CSD characteristics, opening new treatment avenues for CSD and related disorders such as migraine and seizure. Our second study observes the effects of the major non-psychoactive cannabinoid – cannabidiol (CBD) and its acidic precursor – cannabidiolic acid (CBDA) on intrinsic neuron electrophysiological characteristics and on control of neuronal hyperexcitability. This study was motivated by several human reports of the potent anti-epileptic properties of CBD in intractable epilepsies, a void in known mechanisms of actions of CBDA, and a lack of information regarding the effects CBD and CBDA on single neuron and network physiology. We show that CBD and CBDA can control neuronal hyperexcitability in a robust in vitro seizure model. Our findings from this project highlight that CBDA can effectively control neuronal cell properties and seizure-like activity in vitro. The third project examined the neuromodulatory properties of the novel platinum derivative anticancer compounds (RRD4) and oxaliplatin on CA1 pyramidal neurons. Rare cases of chemotherapy-induced seizures during or after administration of platinum- derived agents, like oxaliplatin, are well documented. RRD4 is structurally similar to oxaliplatin, but it contains phosphate groups and showed contrasting effects to RRD4. Oxaliplatin changed intrinsic cell membrane properties, induced hyperexcitability and even caused cell death, while RRD4 only reduced seizure-like hyperexcitability. Advisors/Committee Members: Ziburkus, Jokubas (advisor), Bond, Richard A. (committee member), Chung, Sang-Hyuk (committee member), Dryer, Stuart E. (committee member).

Subjects/Keywords: Neuronal hyperexcitability; Glutamate transporter; Cannabis

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APA (6th Edition):

-9202-6472. (2017). Regulating Neuronal Hyperexcitability: The Role of Glutamate Transport, Cannabinoids, and Platinum-Based Anti-Cancer Drugs. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4821

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Chicago Manual of Style (16th Edition):

-9202-6472. “Regulating Neuronal Hyperexcitability: The Role of Glutamate Transport, Cannabinoids, and Platinum-Based Anti-Cancer Drugs.” 2017. Doctoral Dissertation, University of Houston. Accessed October 31, 2020. http://hdl.handle.net/10657/4821.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

MLA Handbook (7th Edition):

-9202-6472. “Regulating Neuronal Hyperexcitability: The Role of Glutamate Transport, Cannabinoids, and Platinum-Based Anti-Cancer Drugs.” 2017. Web. 31 Oct 2020.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-9202-6472. Regulating Neuronal Hyperexcitability: The Role of Glutamate Transport, Cannabinoids, and Platinum-Based Anti-Cancer Drugs. [Internet] [Doctoral dissertation]. University of Houston; 2017. [cited 2020 Oct 31]. Available from: http://hdl.handle.net/10657/4821.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Council of Science Editors:

-9202-6472. Regulating Neuronal Hyperexcitability: The Role of Glutamate Transport, Cannabinoids, and Platinum-Based Anti-Cancer Drugs. [Doctoral Dissertation]. University of Houston; 2017. Available from: http://hdl.handle.net/10657/4821

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete


University of Toronto

2. Mahadevan, Vivek. Regulation of neuronal Cl- homeostasis and GABAergic inhibition by components of excitatory neurotransmission.

Degree: PhD, 2015, University of Toronto

KCC2 is the neuron-specific member of the K+-Cl- cotransporter family of proteins, which maintains a low intracellular Cl− essential for fast inhibitory synaptic transmission in the mature central nervous system (CNS). KCC2 is essential for survival, as KCC2 knock-out mice die at birth due to respiratory failure. Moreover several neurological disorders including neuropathic pain, epileptic seizures and autism spectrum disorders exhibit impaired synaptic inhibition due to decreased KCC2 expression and function. Despite the critical importance of this protein in maintaining fast synaptic inhibition, KCC2 was discovered to be abundantly expressed at the vicinity of excitatory synapses in 2001. Since this discovery, no study has systematically analyzed how components of synaptic excitation regulate KCC2 function and fast synaptic inhibition in the CNS The principal novel discoveries from my thesis research are: (i) native-KCC2 exists in a multiprotein complex with key members of excitatory synapse namely, the kainate-type ionotropic glutamate receptor (iGluR) subunit GluK2, and its auxiliary subunit Neto2; (ii) these components of excitatory synapse could serve as auxiliary subunits of KCC2 – a concept which was previously non-existent for transporters in general, and in particularly for KCC2; (iii) Neto2 and GluK2 regulates several aspects of KCC2 cellular regulation including total and surface abundance, oligomerization and transporter efficacy in vitro and in vivo; (iv) finally, loss of Neto2 or GluK2 result in impaired KCC2 transporter function in hippocampal neurons. Hence, my discovery represent a novel regulation of KCC2 function and fast synaptic inhibition by components of excitatory transmission, significantly advancing our growing understanding of the tight interplay between excitation and inhibition.

2018-02-12 00:00:00

Advisors/Committee Members: Woodin, Melanie A, Cell and Systems Biology.

Subjects/Keywords: Excitation-inhibition balance; Hyperexcitability; Epilepsy; Neuropathic pain; Neurodevelopmental disorders; GABA; Glutamate; Hippocampus; CNS; Glutamate receptors; Auxiliary subunits; iGluR; Kainate receptors; Multi-protein complex; Neuronal chloride homeostasis; Cation chloride cotransporters; SLC12A5; KCC2; Neto2; GluK2; 0317

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Mahadevan, V. (2015). Regulation of neuronal Cl- homeostasis and GABAergic inhibition by components of excitatory neurotransmission. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/82449

Chicago Manual of Style (16th Edition):

Mahadevan, Vivek. “Regulation of neuronal Cl- homeostasis and GABAergic inhibition by components of excitatory neurotransmission.” 2015. Doctoral Dissertation, University of Toronto. Accessed October 31, 2020. http://hdl.handle.net/1807/82449.

MLA Handbook (7th Edition):

Mahadevan, Vivek. “Regulation of neuronal Cl- homeostasis and GABAergic inhibition by components of excitatory neurotransmission.” 2015. Web. 31 Oct 2020.

Vancouver:

Mahadevan V. Regulation of neuronal Cl- homeostasis and GABAergic inhibition by components of excitatory neurotransmission. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2020 Oct 31]. Available from: http://hdl.handle.net/1807/82449.

Council of Science Editors:

Mahadevan V. Regulation of neuronal Cl- homeostasis and GABAergic inhibition by components of excitatory neurotransmission. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/82449

3. Kras, Jeffrey. The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability.

Degree: 2015, University of Pennsylvania

Traumatic neck injuries commonly result from rear-end motor vehicle collisions and are associated with a high incidence of neck pain and considerable annual costs. The facet joint is the most common source of neck pain. That joint is innervated by nociceptors that are activated by tensile stretching of the joint's capsular ligament. Although activation of those joint afferents and joint inflammation contribute to facet-mediated pain, the cellular response(s) within the joint that initiate pain via the joint afferents are unknown. Similarly, the mechanisms that induce central sensitization and maintain facet pain are not fully defined. Nerve growth factor (NGF) is a potent mediator of inflammatory cascades and is hypothesized to contribute to joint pain. Further, NGF regulates brain-derived neurotrophic factor (BDNF), which, when released in the spinal cord, sensitizes spinal neurons. Despite their roles in inflammatory pain, no studies have identified whether the neurotrophins NGF and/or BDNF contribute to facet joint-mediated pain. These studies utilize a rat model of mechanical facet joint injury to investigate the roles of NGF and BDNF in facet pain. Because joint afferents are crucial for the initiation and maintenance of facet pain, the innervation pattern of the C6/C7 facet joint in the rat is quantitatively defined. NGF expression is measured in the facet joint and the dorsal root ganglion (DRG) following a painful facet joint distraction. Further, the role of intra-articular NGF in the initiation and maintenance of facet-mediated pain and spinal neuronal hyperexcitability is evaluated by selectively blocking intra-articular NGF signaling. BDNF expression is quantified in the DRG and spinal cord after joint injury. Selective inhibition of spinal BDNF is utilized to determine its contribution to facet-mediated pain. This thesis demonstrates that throughout the peripheral and central nervous systems neurotrophins are key mediators of behavioral hypersensitivity and contribute to the hyperexcitability of spinal neurons after a painful facet joint injury. This work further establishes the need for future studies to integrate investigations throughout all aspects of the pain pathway to fully understand the mechanisms underlying facet-mediated pain.

Subjects/Keywords: Brain-Derived Neurotrophic Factor; Facet Joint; Injury; Nerve Growth Factor; Neuronal Hyperexcitability; Pain; Biomedical; Engineering

…Articular NGF-Induced Pain & Neuronal Hyperexcitability.......101 5.4.4 Blocking Intra-Articular… …associated with spinal neuronal hyperexcitability… …NGF-induced behavioral sensitivity or neuronal hyperexcitability .........106 Figure 5.8… …modulates the development of FJD-induced pain and spinal neuronal hyperexcitability at day one… …neuronal hyperexcitability… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Kras, J. (2015). The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/1078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Kras, Jeffrey. “The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability.” 2015. Thesis, University of Pennsylvania. Accessed October 31, 2020. https://repository.upenn.edu/edissertations/1078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Kras, Jeffrey. “The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability.” 2015. Web. 31 Oct 2020.

Vancouver:

Kras J. The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability. [Internet] [Thesis]. University of Pennsylvania; 2015. [cited 2020 Oct 31]. Available from: https://repository.upenn.edu/edissertations/1078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kras J. The Role of Intra-Articular Nerve Growth Factor in Facet-Mediated Pain: Relationships to Spinal BDNF and Neuronal Hyperexcitability. [Thesis]. University of Pennsylvania; 2015. Available from: https://repository.upenn.edu/edissertations/1078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.