Remote and Persistent Alterations in Glutamate Receptor Subunit Composition Induced by Spreading Depolarizations in Rat Brain

Barhorst, Kinsey; Alfawares, Yara; McGuire, Jennifer L.; Danzer, Steve C.; Hartings, Jed A.; Ngwenya, Laura B.

doi:10.1007/s10571-020-01000-3

Cited by 5 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After hypoxia injury in rats, MLT administration reduced glutamate levels and hypoxiainduced structural damage to neurons, axons, and dendrites in the brainstem, suggesting that it can ameliorate excitotoxic injury (Kaur et al, 2011). Notably, gamma-aminobutyric acid and glutamate neurotransmitters are causally related to the neuroexcitability influences on CSD (Lima et al, 2009;Barhorst et al, 2022).…”

Section: Discussionmentioning

confidence: 98%

Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats

Araújo,

Figueira-de-Oliveira,

Noya

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

IntroductionMelatonin (MLT) reportedly has beneficial effects in neurological disorders involving brain excitability (e.g., Epilepsy and Migraine) and behavioral patterns (e.g., Anxiety and Depression). This study was performed to investigate, in the developing rat brain, the effect of early-in-life administration of two different doses of exogenous MLT on behavioral (anxiety and memory) and electrophysiological (CSD analysis) aspects of brain function. Additionally, brain levels of malondialdehyde (MDA) and superoxide dismutase (SOD), both cellular indicators of redox balance status, were evaluated. We hypothesize that MLT differentially affects the behavioral and CSD parameters as a function of the MLT dose.Materials and methodsMale Wistar rats received, from the 7th to the 27th postnatal day (PND), on alternate days, vehicle solution, or 10 mg/kg/or 40 mg/kg MLT (MLT-10 and MLT-40 groups), or no treatment (intact group). To perform behavioral and cognition analysis, from PND30 to PND32, they were tested in the open field apparatus, first for anxiety (PND30) and then for object recognition memory tasks: spatial position recognition (PND31) and shape recognition (PND32). On PND34, they were tested in the elevated plus maze. From PND36 to 42, the excitability-related phenomenon known as cortical spreading depression (CSD) was recorded, and its features were analyzed.ResultsTreatment with MLT did not change the animals’ body weight or blood glucose levels. The MLT-10 treatment, but not the MLT-40 treatment, was associated with behaviors that suggest less anxiety and improved memory. MLT-10 and MLT-40 treatments, respectively, decelerated and accelerated CSD propagation (speed of 2.86 ± 0.14 mm/min and 3.96 ± 0.16 mm/min), compared with the control groups (3.3 ± 0.10 mm/min and 3.25 ± 0.11 mm/min, for the intact and vehicle groups, respectively; p < 0.01). Cerebral cortex levels of malondialdehyde and superoxide dismutase were, respectively, lower and higher in the MLT-10 group but not in the MLT40 group.ConclusionOur findings suggest that MLT intraperitoneal administration during brain development may differentially act as an antioxidant agent when administered at a low dose but not at a high dose, according to behavioral, electrophysiological, and biochemical parameters.

show abstract

Section: Discussionmentioning

confidence: 98%

Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats

Araújo,

Figueira-de-Oliveira,

Noya

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The tissue was homogenized in an mPER and protease inhibitor cocktail (100×). Western blots were performed following a previously optimized protocol [ 26 ]. A BCA assay was conducted to determine the protein concentration of each sample.…”

Section: Methodsmentioning

confidence: 99%

“…Spreading depolarizations are episodes of extensive neuronal depolarization resulting in loss of neuronal ion homeostasis and a period of electrical silencing [ 25 ]. This activity spreads across the contiguous cortex and can be induced in many brain regions, including the hippocampus [ 26 ]. These spreading depolarizations have been shown to be a prominent pathology in patients with TBI and prognosticate a worse outcome [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…We investigated glutamatergic signaling in the rat model of depression (WKY) compared with its parent Wistar strain (WIS) after a moderate LFPI. We examined the glutamate receptor subunit expression in the hippocampal dentate gyrus, as we have previously shown changes in glutamate signaling in the hippocampus and because of the now recognized importance of this neurotransmitter system in both TBI and depression [ 20 , 21 , 26 ]. In addition, we also examined hippocampal volume and cell proliferation, as these are known histopathological features of MDD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lack of Glutamate Receptor Subunit Expression Changes in Hippocampal Dentate Gyrus after Experimental Traumatic Brain Injury in a Rodent Model of Depression

Knott

Ngwenya

Correll

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Traumatic brain injury (TBI) affects over 69 million people annually worldwide, and those with pre-existing depression have worse recovery. The molecular mechanisms that may contribute to poor recovery after TBI with co-morbid depression have not been established. TBI and depression have many commonalities including volume changes, myelin disruption, changes in proliferation, and changes in glutamatergic signaling. We used a well-established animal model of depression, the Wistar Kyoto (WKY) rat, to elucidate changes after TBI that may influence the recovery trajectory. We compared the histological and molecular outcomes in the hippocampal dentate gyrus after experimental TBI using the lateral fluid percussion injury (LFPI) in the WKY and the parent Wistar (WIS) strain. We showed that WKY had exaggerated myelin loss after LFPI and baseline deficits in proliferation. In addition, we showed that while after LFPI WIS rats exhibited glutamate receptor subunit changes, namely increased GluN2B, the WKY rats failed to show such injury-related changes. These differential responses to LFPI helped to elucidate the molecular characteristics that influence poor recovery after TBI in those with pre-existing depression and may lead to targets for future therapeutic interventions.

show abstract

“…However, as Navratilova and colleagues describe, once central sensitization has set in, there are certainly CGRPindependent physiologies as well. Similarly, while glutamate is highly implicated in the acute phase of TBI leading to cortical spreading depression, there may also be persistent changes to glutamate receptor composition [26].…”

Section: Persistent Pth Treatment Modelsmentioning

confidence: 99%

Models for Treating Post-traumatic Headache

Kamins

2021

Curr Pain Headache Rep

View full text Add to dashboard Cite

Purpose of Review To discuss the treatment of post-traumatic headache (PTH) and how to choose pharmacotherapy based upon known pathophysiology. Recent Findings Preclinical models of traumatic brain injury are finally revealing some of the mechanisms of PTH, including the significant role that inflammatory neuropeptides like calcitonin gene-related peptide (CGRP) play in the initiation and persistence of symptoms. Summary To effectively treat post-traumatic headache (PTH), one needs to understand the pathophysiology behind the initiation and persistence of symptoms. Recent animal models are starting to elucidate these mechanisms, but effective treatment will also likely rely on the identification of patients who are most at risk for persistent PTH. Trials of early, targeted therapy for at-risk patients will be needed to validate these hypotheses. Additionally, high powered clinical trials are lacking in the field of persistent PTH for medications that are known to be effective in primary headache disorders. Effective treatment for persistent PTH also requires understanding how headache interacts with the complex nature of persistent post-concussion symptoms, as this disease often necessitates a multi-disciplinary approach. Regardless, with the knowledge gained by new PTH models cited in this paper, and an increasing availability of novel headache medications, more effective treatment models are on the horizon.

show abstract

Remote and Persistent Alterations in Glutamate Receptor Subunit Composition Induced by Spreading Depolarizations in Rat Brain

Cited by 5 publications

References 34 publications

Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats

Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats

Lack of Glutamate Receptor Subunit Expression Changes in Hippocampal Dentate Gyrus after Experimental Traumatic Brain Injury in a Rodent Model of Depression

Models for Treating Post-traumatic Headache

Contact Info

Product

Resources

About