Publications by authors named "Donna M Geddes-Klein"

NMDA receptors are essential for neurotransmission and key mediators of synaptic signaling, but they can also trigger deleterious degenerative processes that lead to cell death. Growing evidence suggests that selective blockade of the heterogeneous subunits that comprise the NMDA receptor may enable better control of pharmacotherapies for treating neurological diseases and injuries. We investigated the relationship between NMDAR activation, MAPK signaling, and mitochondrial shape following an excitotoxic insult.

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N-methyl-D-aspartate receptors (NMDARs), critical mediators of both physiologic and pathologic neurological signaling, have previously been shown to be sensitive to mechanical stretch through the loss of its native Mg(2+) block. However, the regulation of this mechanosensitivity has yet to be further explored. Furthermore, as it has become apparent that NMDAR-mediated signaling is dependent on specific NMDAR subtypes, as governed by the identity of the NR2 subunit, a crucial unanswered question is the role of subunit composition in observed NMDAR mechanosensitivity.

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Traumatic brain injury (TBI) represents one of most common disorders to the central nervous system (CNS). Despite significant efforts, though, an effective clinical treatment for TBI is not yet available. The complexity of human TBI is modeled with a broad group of experimental models, with each model matching some aspect of the human condition.

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Increases in cytosolic calcium ([Ca(2+)](i)) following mechanical injury are often considered a major contributing factor to the cellular sequelae in traumatic brain injury (TBI). However, very little is known on how developmental changes may affect the calcium signaling in mechanically injured neurons. One key feature in the developing brain that may directly impact its sensitivity to stretch is the reduced inhibition which results in spontaneous [Ca(2+)](i) oscillations.

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The deformation to the brain that occurs during traumatic brain injury (TBI) results in a complex strain distribution throughout the brain tissue. Recently, many in vitro models of neuronal injury have been developed to simplify the mechanics which occur during TBI. We hypothesized that the type of mechanical insult imparted onto neurons would significantly alter both the mechanism and severity of the neuronal response to injury.

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Synopsis of recent research by authors named "Donna M Geddes-Klein"

  • Donna M Geddes-Klein's research primarily focuses on the mechanisms of neuronal injury and protective responses, particularly in the context of traumatic brain injury (TBI) and excitotoxicity, exploring the roles of NMDA receptor subunits in mediating signaling pathways and cellular outcomes.
  • Her findings indicate that the specific subunits of NMDA receptors (NR2A and NR2B) differentially influence MAPK signaling and mitochondrial morphology following excitotoxic insults, offering insights into potential pharmacological strategies for treating neurological conditions.
  • Geddes-Klein's work emphasizes the complexity of TBI and suggests that the mechanics of neuronal injury can significantly affect cellular responses, highlighting the importance of model selection in understanding the pathophysiology of brain injuries.