Recent advances in the role of excitation–inhibition balance in motor recovery post-stroke

Grigoras, Ioana; Stagg, Charlotte J.

doi:10.12703/r/10-58

Cited by 24 publications

(14 citation statements)

References 84 publications

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“…However, not all the groups showed the showed the bene cial role in functional recovery. The signi cant motor recovery was only shown in PV-ChR2 group There have been many trials to measure the GABA level with controversial results 55 . We found that two types of GABA exist in PV-ChR2 group; GABA released from reactive astrocyte after Wallerian degeneration in the cortex and neuronal GABA released from PV-expressing neurons in capsular infarct model 21 .…”

Section: Discussionmentioning

confidence: 99%

Neuron-type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Kim,

Cho

et al. 2023

Preprint

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Cortical electrical stimulation (CNM) is widely used to promote recovery after stroke. Despite beneficial results, current CNM techniques are unable to differentiate the roles played by different neuron types in their effects. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to post-stroke recovery. We transduced sensory-parietal cortex (SPC) in rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons produced significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed the significant reduction of cortical diaschisis and activation of corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could enhance post-stroke outcomes.

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Section: Discussionmentioning

confidence: 99%

Neuron-type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Kim,

Cho

et al. 2023

Preprint

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“…41,42 Alternatively, pharmacological agents to modify E/I ratio are available. 43 Therefore, in future stroke, rehabilitation studies spectral exponents could serve as a novel biomarker to identify individuals that might profit from a targeted therapy and simultaneously monitor the effect of such an intervention.…”

Section: Discussionmentioning

confidence: 99%

Normalization of Aperiodic Electrocorticography Components Indicates Fine Motor Recovery After Sensory Cortical Stroke in Mice

Biskamp

Cainzos

Higgen

et al. 2022

Stroke

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BACKGROUND: Electrophysiological signatures of ischemic stroke might help to develop a deeper understanding of the mechanisms of recovery. However, to identify critical windows for novel treatment approaches, suitable readout parameters in vivo with the potential to close the gap between functional modifications within the peri-infarct cortex and behavioral outcome on the systems-level are still lacking. METHODS: Wild-type mice were trained in a skilled reaching task and underwent permanent distal medial cerebral artery occlusion or sham intervention. Functional deficits and their recovery were monitored both behaviorally and electrophysiologically recording multichannel electrocorticography from both hemispheres. RESULTS: Ischemic strokes are located in sensory cortical areas. Affected mice presented fine motor deficits of their contralateral forepaw. Analyses of electrocorticography signals from awake animals demonstrated a modulation of the shape of power spectral density in the vicinity of the infarct. While power spectral density consists of both rhythmic oscillatory and nonrhythmic, aperiodic components, the alteration of spectrum shape was reflected in a transient increase of aperiodic exponents in the peri-infarct cortex. The relative power and frequency of slow oscillations remained unchanged. Exponents derived from motor areas significantly correlated with fine motor recovery, thus indicating functional modifications of neuronal activity. CONCLUSIONS: Aperiodic spectral exponents exhibited a unique spatiotemporal profile in the mouse cortex after stroke and might complement future translational studies providing a dynamic link from pathophysiology to behavior.

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“…Commensurate with decreased inhibitory drive in epilepsy, there is an increase in glutamate-receptor mediated excitability, in part due to alterations in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-Daspartate receptor (NMDAR) subunits expression, with increases in the ratios of GluA1/GluA2 AMPAR subunits and GluN2B/GluN2A NMDAR subunits resulting in GluA2-lacking, Ca 2+permeable AMPAR [26][27][28] and extended decay times and elevated Ca 2+ influx, respectively [29][30][31] . Pathologic E:I alterations are not unique to epilepsy, as evidence for neuronal hyperexcitability has been seen in other neurodevelopmental and neurodegenerative disorders [32][33][34][35] . In AD patients, altered GABAAR subunit regulation has been observed 36 , including decreased α1/α3 expression 37 .…”

Section: Introductionmentioning

confidence: 99%

Excitatory: inhibitory imbalance in Alzheimer’s disease is exacerbated by seizures with attenuation after rapamycin treatment in 5XFAD mice

Barbour

Gourmaud

et al. 2023

Preprint

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Increasing evidence indicates a bidirectional relationship between epilepsy and Alzheimer’s disease (AD) with 22% of AD patients additionally suffering from seizures, which may be a targetable component of disease progression. Since epileptogenesis is associated with changes in excitatory: inhibitory (E:I) balance, we examined postmortem AD brain tissue from patients with and without seizure history and five times familial AD (5XFAD) mice for changes in several markers of E:I balance, including the inhibitory GABAAreceptor, the chloride cotransporters, sodium potassium chloride cotransporter 1 (NKCC1) and potassium chloride cotransporter 2 (KCC2), and the excitatory NMDA and AMPA type glutamate receptors. We hypothesized that seizure history in AD patients would be associated with greater E:I imbalances, and that such changes would also be observed in the 5XFAD mice following pentylenetetrazol (PTZ) kindling. We found that seizures in AD patients were associated with alterations in NKCC1 and KCC2 expression, indicative of depolarizing GABA, and exacerbated cognitive deficits. Seizures also significantly contributed to E:I imbalance in the 5XFAD mouse model, as similar changes in NKCC1 and KCC2 expression were found in PTZ treated 5XFAD mice, along with altered AMPA receptor protein expression indicative of calcium permeable-AMPA receptors. In addition, we found that chronic treatment with the mTOR inhibitor rapamycin at doses we have previously shown to attenuate seizure-inducedβ-amyloid pathology and cognitive deficits in 5XFAD mice, can mitigate the dysregulation of markers of E:I balance in this model. These data suggest that mTOR activation plays a role in modifying the E:I imbalance and network hyperexcitability in AD and that the FDA-approved mTOR inhibitors such as rapamycin may have potential for therapy in AD patients with a seizure history.

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Recent advances in the role of excitation–inhibition balance in motor recovery post-stroke

Cited by 24 publications

References 84 publications

Neuron-type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Neuron-type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Normalization of Aperiodic Electrocorticography Components Indicates Fine Motor Recovery After Sensory Cortical Stroke in Mice

Excitatory: inhibitory imbalance in Alzheimer’s disease is exacerbated by seizures with attenuation after rapamycin treatment in 5XFAD mice

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