Gordon S. Mitchell
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View article: Phrenic Long-Term Facilitation Following Acute Intermittent Hypercapnic-Hypoxia in Rats
Phrenic Long-Term Facilitation Following Acute Intermittent Hypercapnic-Hypoxia in Rats Open
Phrenic long-term facilitation (pLTF) is a form of respiratory motor plasticity, expressed as a lasting increase in phrenic nerve activity following acute intermittent hypoxia (AIH). Whereas AIH also elicits ventilatory LTF (vLTF) in unane…
View article: Phrenic long-term facilitation following severe acute intermittent hypoxia is preserved in geriatric male rats
Phrenic long-term facilitation following severe acute intermittent hypoxia is preserved in geriatric male rats Open
We report new findings that advance our understanding of how cellular mechanisms underlying respiratory motor plasticity shift with age. Age-related shifts in the magnitude or mechanism driving plasticity have major clinical relevance as w…
View article: Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial
Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial Open
Background Respiratory impairment is a major concern in amyotrophic lateral sclerosis (ALS), shortening survival and lowering quality of life. One therapy with promise to delay respiratory decline in ALS is acute intermittent hypoxia (AIH)…
View article: Increased spinal adenosine after subacute cervical injury correlates with sustained upregulation of CD39 and CD73 in microglia
Increased spinal adenosine after subacute cervical injury correlates with sustained upregulation of CD39 and CD73 in microglia Open
Cervical spinal cord injuries (cSCI) are associated with decreased breathing ability. Although no treatment options are currently available, moderate acute intermittent hypoxia (mAIH) is a promising therapeutic modality to improve breathin…
View article: Characterization of Ventilatory Drive in Community-Dwelling Adults with Chronic Spinal Cord Injury
Characterization of Ventilatory Drive in Community-Dwelling Adults with Chronic Spinal Cord Injury Open
Independently breathing adults with chronic SCI have P0.1 values within normal range. This suggests their intrinsic resting ventilatory drive recovers from potentially elevated states in the acute phase of injury and is sufficient to susta…
View article: Rodent Breathing Waveforms in ApoE Rats: Statistical and Entropic Differentiation.
Rodent Breathing Waveforms in ApoE Rats: Statistical and Entropic Differentiation. Open
Apolipoprotein E (ApoE) gene variations are involved in lipid metabolism and cholesterol transport, with the ApoE4 allele being a known risk factor associated with neurodegenerative conditions later in life. Emerging evidence suggests thes…
View article: Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial (Preprint)
Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial (Preprint) Open
BACKGROUND Respiratory impairment is a major concern in amyotrophic lateral sclerosis (ALS), shortening survival and lowering quality of life. One therapy with promise to delay respiratory decline in ALS is acute intermittent hypoxia (AIH…
View article: Daily acute intermittent hypoxia elicits age & sex-dependent changes in molecules regulating phrenic motor plasticity
Daily acute intermittent hypoxia elicits age & sex-dependent changes in molecules regulating phrenic motor plasticity Open
Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Exposure to repetitive daily AIH (dAIH) enhances pLTF, a form of metaplasticity. Little is known concerning cel…
View article: Ventilatory long-term facilitation at rest increases the feedforward contribution to subsequent exercise ventilatory responses
Ventilatory long-term facilitation at rest increases the feedforward contribution to subsequent exercise ventilatory responses Open
We demonstrate that by inducing ventilatory long-term facilitation (LTF) at rest, subsequent ventilatory responses to mild or moderate exercise are altered. When ventilatory LTF was induced via hypercapnic acute intermittent hypoxia, the f…
View article: A case report of long-latency evoked diaphragm potentials after exposure to acute intermittent hypoxia in post-West Nile virus meningoencephalitis
A case report of long-latency evoked diaphragm potentials after exposure to acute intermittent hypoxia in post-West Nile virus meningoencephalitis Open
A 42-year-old female with post-West Nile virus meningoencephalitis demonstrated long-latency diaphragmatic potentials evoked by transcranial and cervical magnetic stimulation following exposure to acute intermittent hypoxia that were not p…
View article: Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling
Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling Open
We report an important role for microglia in regulating neuroplasticity within phrenic motor neurons. Brief episodes of low oxygen (acute intermittent hypoxia; AIH) elicit a form of respiratory motor plasticity known as phrenic long-term f…
View article: Acute postnatal inflammation alters adult microglial responses to LPS that are sex-, region- and timing of postnatal inflammation-dependent
Acute postnatal inflammation alters adult microglial responses to LPS that are sex-, region- and timing of postnatal inflammation-dependent Open
View article: Cardiopulmonary adaptations of a diving marine mammal, the bottlenose dolphin: Physiology during anesthesia
Cardiopulmonary adaptations of a diving marine mammal, the bottlenose dolphin: Physiology during anesthesia Open
Diving marine mammals are a diverse group of semi‐ to completely aquatic species. Some species are targets of conservation and rehabilitation efforts; other populations are permanently housed under human care and may contribute to clinical…
View article: Acute Postnatal Inflammation Alters Adult Microglial Responses to LPS that Are Sex-, Region- and Timing of Postnatal Inflammation-Dependent
Acute Postnatal Inflammation Alters Adult Microglial Responses to LPS that Are Sex-, Region- and Timing of Postnatal Inflammation-Dependent Open
Background. Adverse events in early life can have impact lasting into adulthood. We investigated the long-term effects of systemic inflammation during postnatal development on adult microglial responses to LPS in two CNS regions (cortex, c…
View article: Microglia regulate motor neuron plasticity via reciprocal fractalkine/adenosine signaling
Microglia regulate motor neuron plasticity via reciprocal fractalkine/adenosine signaling Open
Microglia are innate CNS immune cells that play key roles in supporting key CNS functions including brain plasticity. We now report a previously unknown role for microglia in regulating neuroplasticity within spinal phrenic motor neurons, …
View article: Daily Acute Intermittent Hypoxia Elicits Age & Sex-Dependent Changes in Molecules Regulating Phrenic Motor Plasticity
Daily Acute Intermittent Hypoxia Elicits Age & Sex-Dependent Changes in Molecules Regulating Phrenic Motor Plasticity Open
Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (LTF). Repetitive daily AIH (dAIH) exposure enhances phrenic LTF, demonstrating a form of metaplasticity. Two additiona…
View article: Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons
Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons Open
We report important new findings concerning the mechanisms regulating a form of spinal neuroplasticity elicited by prolonged inhibition of respiratory neural activity, inactivity-induced phrenic motor facilitation (iPMF). We demonstrate th…
View article: Inaugural Review Prize 2023: The exercise hyperpnoea dilemma: A 21st‐century perspective
Inaugural Review Prize 2023: The exercise hyperpnoea dilemma: A 21st‐century perspective Open
During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO 2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over…
View article: Progressive tauopathy disrupts breathing stability and chemoreflexes during presumptive sleep in mice
Progressive tauopathy disrupts breathing stability and chemoreflexes during presumptive sleep in mice Open
Rationale: Although sleep apnea occurs in over 50% of individuals with Alzheimer’s Disease (AD) or related tauopathies, little is known concerning the potential role of tauopathy in the pathogenesis of sleep apnea. Here, we tested the hypo…
View article: Increased spinal adenosine impairs phrenic long-term facilitation in aging rats
Increased spinal adenosine impairs phrenic long-term facilitation in aging rats Open
Advanced age undermines respiratory motor plasticity, specifically phrenic long-term facilitation (pLTF) following moderate acute intermittent hypoxia (mAIH). We report that spinal adenosine increases in aged male rats, undermining mAIH-in…
View article: Mild inflammation impairs acute intermittent hypoxia-induced phrenic long-term facilitation by a spinal adenosine-dependent mechanism
Mild inflammation impairs acute intermittent hypoxia-induced phrenic long-term facilitation by a spinal adenosine-dependent mechanism Open
Mild inflammation undermines motor plasticity elicited by mAIH. In a model of mAIH-induced respiratory motor plasticity (phrenic long-term facilitation; pLTF), we report that inflammation induced by low-dose lipopolysaccharide undermines m…
View article: A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO <sub>2</sub> ST Trial
A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO <sub>2</sub> ST Trial Open
Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALK tSTIM ) …
View article: BDNF-induced phrenic motor facilitation shifts from PKCθ to ERK dependence with mild systemic inflammation
BDNF-induced phrenic motor facilitation shifts from PKCθ to ERK dependence with mild systemic inflammation Open
We demonstrate that even mild systemic inflammation shifts signaling mechanisms giving rise to BDNF-induced phrenic motor plasticity. This finding has important experimental, biological, and translational implications, particularly since B…
View article: APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia
APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia Open
Rationale Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials repor…
View article: APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia
APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia Open
Rationale Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual response…
View article: Magnitude and Mechanism of Phrenic Long-term Facilitation Shift Between Daily Rest Versus Active Phase
Magnitude and Mechanism of Phrenic Long-term Facilitation Shift Between Daily Rest Versus Active Phase Open
Plasticity is a fundamental property of the neural system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic nerve activity elicited by acute in…
View article: Daily fluctuations in spinal adenosine determine mechanisms of respiratory motor plasticity
Daily fluctuations in spinal adenosine determine mechanisms of respiratory motor plasticity Open
Plasticity is a fundamental property of the neuromotor system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic nerve activity after exposure t…
View article: Dose-dependent phosphorylation of endogenous Tau by intermittent hypoxia in rat brain
Dose-dependent phosphorylation of endogenous Tau by intermittent hypoxia in rat brain Open
Sleep apnea is highly prevalent in people with Alzheimer’s disease, suggesting the potential to accelerate disease onset and/or progression. These studies demonstrate that intermittent hypoxia (IH) induces dose-dependent, region-specific T…
View article: Caffeine Enhances Intermittent Hypoxia-Induced Gains in Walking Function for People with Chronic Spinal Cord Injury
Caffeine Enhances Intermittent Hypoxia-Induced Gains in Walking Function for People with Chronic Spinal Cord Injury Open
Incomplete spinal cord injury (iSCI) often results in lifelong walking impairments that limit functional independence. Thus, treatments that trigger enduring improvement in walking after iSCI are in high demand. Breathing brief episodes of…
View article: Acute intermittent hypercapnic‐hypoxia elicits central neural respiratory motor plasticity in humans
Acute intermittent hypercapnic‐hypoxia elicits central neural respiratory motor plasticity in humans Open
Acute intermittent hypoxia (AIH) elicits long‐term facilitation (LTF) of respiration. Although LTF is observed when CO 2 is elevated during AIH in awake humans, the influence of CO 2 on corticospinal respiratory motor plasticity is unknown…