Reducing GABAA-mediated inhibition improves forelimb motor function after focal cortical stroke in mice

Alia, Claudia; Spalletti, Cristina; Lai, Stefano; Panarese, Alessandro; Micera, Silvestro; Caleo, Matteo

doi:10.1038/srep37823

Cited by 65 publications

(79 citation statements)

References 86 publications

(139 reference statements)

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“…Glu‐Gln cycle is involved in the Glu synthesis from Gln, while Glu acts as a precursor for GABA synthesis (Meldrum, ). Key modulators of post‐stroke neuronal plasticity are GABA, mI, Glu, Gln, and NAA (Cristea et al, ; Alia et al, ). In a photothrombotic stroke model, inhibition of GABAergic signaling restored motor functions, and Glu‐induced excitotoxicity was associated with elevated MMP‐9 activity (Michaluk & Kaczmarek., ; Alia et al, ).…”

Section: Discussionmentioning

confidence: 99%

Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Gupta

Upadhayay

Sharma

et al. 2018

J of Neuroscience Research

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Oxidative stress and inflammation are implicated as cardinal mechanisms of neuronal death following stroke. In the present study citalopram (Cit) was investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8 mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post-MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of Cit (4 mg/kg) was administered i.p., 0.5 h post-reperfusion (Post Cit) only, and 1 h prior to MCAo and again at 0.5 h post-reperfusion (Pre + Post Cit), respectively. These two groups were assessed for NDS and cerebral infarction. Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups, significant reduction in cerebral infarction was evident only in Pre + Post Cit group. Infarct volume assessed by magnetic resonance imaging was significantly attenuated in Pre + Post Cit group (10.6 ± 1.1%) compared to MCAo control group (18.5 ± 3.0%). Further, Pre + Post Cit treatment significantly altered 17 metabolites along with attenuation of malondialdehyde, reduced glutathione, matrix metalloproteinases, and apoptotic markers as compared to MCAo control. These results support the neuroprotective effect of Cit, mediated through amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic profile.

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Section: Discussionmentioning

confidence: 99%

Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Gupta

Upadhayay

Sharma

et al. 2018

J of Neuroscience Research

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“…In animal models, reorganization of motor maps has been observed using intracortical microstimulation (ICMS; Nudo and Milliken, 1996; Nishibe et al, 2010; Alia et al, 2016) or optogenetic techniques (Harrison et al, 2013). …”

Section: Neuroplasticity After Strokementioning

confidence: 99%

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Alia

Spalletti

Lai

et al. 2017

Front. Cell. Neurosci.

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165

119

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Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration.

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“…Under avertin anesthesia (intraperitoneal injection of 2,2,2-tribromoethanol solution; 250 mg/kg body weight; Sigma Aldrich, USA), mice received a stereotaxically guided injection of 40,000 GL261 cells as described (Vannini et al, 2016(Vannini et al, , 2017. In C57BL/6J, Thy1-ChR2 and PV-Cre mice, cells were injected either into the primary visual cortex (Vannini et al, 2016) or into the motor cortex (Vannini et al, 2017) in correspondence with the forelimb representation (caudal forelimb area (Alia et al, 2016;Allegra Mascaro et al, 2019)).…”

Section: Tumor Inductionmentioning

confidence: 99%

Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation

Tantillo

Vannini

Cerri

et al. 2020

Preprint

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AbstractRecent studies have demonstrated an active role for neurons in glioma progression. Specifically, peritumoral neurons establish functional excitatory synapses with glioma cells, and optogenetic stimulation of cortical pyramidal neurons drives tumor progression. However, the specific role of different subsets of cortical neurons, such as GABAergic interneurons, remains unexplored. Here, we directly compared the effects of optogenetic stimulation of pyramidal cells vs. fast-spiking, GABAergic neurons. In mice inoculated with GL261 cells into the motor cortex, we show that optogenetic stimulation of pyramidal neurons enhances glioma cell proliferation. In contrast, optogenetic stimulation of fast-spiking, parvalbumin-positive interneurons reduces proliferation as measured by BrdU incorporation and Ki67 immunolabelling. Since both principal cells and fast-spiking interneurons are directly activated by sensory afferent input, we next placed tumors in the occipital cortex to test the impact of visual stimulation/deprivation. We report that total lack of visual input via dark rearing enhances the density of proliferating glioma cells, while daily visual stimulation by gratings of different spatial frequencies and contrast reduces tumor growth. The effects of sensory input are region-specific, as visual deprivation has no significant effect on tumor proliferation in mice with gliomas in the motor cortex. We also report that sensory stimulation combined with temozolomide administration delays the loss of visual responses in peritumoral neurons. Altogether, these data demonstrate complex effects of different neuronal subtypes in the control of glioma proliferation.HighlightsActivity of GABAergic neurons reduces glioma cell proliferationLevels of sensory afferent input regulate tumor proliferationEffects of sensory input are region-specific

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Reducing GABAA-mediated inhibition improves forelimb motor function after focal cortical stroke in mice

Cited by 65 publications

References 86 publications

Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation

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