Oxytocin Exhibits Neuroprotective Effects on Hippocampal Cultures under Severe Oxygen-Glucose Deprivation Conditions.

Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen-glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may confound any measured treatment effect. Oxytocin (OXT) has emerged as a potential neuroprotective agent against the deleterious effects of PA. Previous studies have demonstrated OXT's potential to enhance neuronal survival in immature hippocampal cultures exposed to OGD, possibly by modulating gamma-aminobutyric acid-A receptor activity. Moreover, OXT's precise impact on developing hippocampal neurons under different severities of OGD/PA remains uncertain. In this study, we investigated the effects of OXT (0.1 µM and 1 µM) on 7-day-old primary rat hippocampal cultures subjected to 2 h OGD/sham normoxic conditions. Cell culture viability was determined using the resazurin assay. Our results indicate that the efficacy of 1 µM OXT treatment varied according to the severity of the OGD-induced lesion, exhibiting a protective effect (p = 0.022) only when cellular viability dropped below 49.41% in non-treated OGD cultures compared to normoxic ones. Furthermore, administration of 0.1 µM OXT did not yield significant effects, irrespective of lesion severity (p > 0.05). These findings suggest that 1 µM OXT treatment during OGD confers neuroprotection exclusively in severe lesions in hippocampal neurons after 7 days in vitro. Further research is warranted to elucidate the mechanisms involved in OXT-mediated neuroprotection.

Investigating Different Levels of Bimanual Interaction With a Novel Motor Learning Task: A Behavioural and Transcranial Alternating Current Stimulation Study.

Many tasks require the skilled interaction of both hands, such as eating with knife and fork or keyboard typing. However, our understanding of the behavioural and neurophysiological mechanisms underpinning bimanual motor learning is still sparse. Here, we aimed to address this by first characterising learning-related changes of different levels of bimanual interaction and second investigating how beta tACS modulates these learning-related changes. To explore early bimanual motor learning, we designed a novel bimanual motor learning task. In the task, a force grip device held in each hand (controlling x- and y-axis separately) was used to move a cursor along a path of streets at different angles (0°, 22.5°, 45°, 67.5°, and 90°). Each street corresponded to specific force ratios between hands, which resulted in different levels of hand interaction, i.e., unimanual (Uni, i.e., 0°, 90°), bimanual with equal force (Bi eq , 45°), and bimanual with unequal force (Bi uneq 22.5°, 67.5°). In experiment 1, 40 healthy participants performed the task for 45 min with a minimum of 100 trials. We found that the novel task induced improvements in movement time and error, with no trade-off between movement time and error, and with distinct patterns for the three levels of bimanual interaction. In experiment 2, we performed a between-subjects, double-blind study in 54 healthy participants to explore the effect of phase synchrony between both sensorimotor cortices using tACS at the individual's beta peak frequency. The individual's beta peak frequency was quantified using electroencephalography. 20 min of 2 mA peak-to-peak amplitude tACS was applied during task performance (40 min). Participants either received in-phase (0° phase shift), out-of-phase (90° phase shift), or sham (3 s of stimulation) tACS. We replicated the behavioural results of experiment 1, however, beta tACS did not modulate motor learning. Overall, the novel bimanual motor task allows to characterise bimanual motor learning with different levels of bimanual interaction. This should pave the way for future neuroimaging studies to further investigate the underlying mechanism of bimanual motor learning.

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

Stroke affects millions of people worldwide each year, and stroke survivors are often left with motor deficits. Current therapies to improve these functional deficits are limited, making it a priority to better understand the pathophysiology of stroke recovery and find novel adjuvant options. The excitation-inhibition balance undergoes significant changes post-stroke, and the inhibitory neurotransmitter γ-aminobutyric acid (GABA) appears to play an important role in stroke recovery. In this review, we summarise the most recent studies investigating GABAergic inhibition at different stages of stroke. We discuss the proposed role of GABA in counteracting glutamate-mediated excitotoxicity in hyperacute stroke as well as the evidence linking decreased GABAergic inhibition to increased neuronal plasticity in early stroke. Then, we discuss two types of interventions that aim to modulate the excitation-inhibition balance to improve functional outcomes in stroke survivors: non-invasive brain stimulation (NIBS) and pharmacological interventions. Finding the optimal NIBS administration or adjuvant pharmacological therapies would represent an important contribution to the currently scarce therapy options.

Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation.

Neuronal ischemia results in chloride gradient alterations which impact the excitatory-inhibitory balance, volume regulation, and neuronal survival. Thus, the Na+/K+/Cl- co-transporter (NKCC1), the K+/ Cl- co-transporter (KCC2), and the gamma-aminobutyric acid A (GABAA) receptor may represent therapeutic targets in stroke, but a time-dependent effect on neuronal viability could influence the outcome. We, therefore, successively blocked NKCC1, KCC2, and GABAA (with bumetanide, DIOA, and gabazine, respectively) or activated GABAA (with isoguvacine) either during or after oxygen-glucose deprivation (OGD). Primary hippocampal cultures were exposed to a 2-h OGD or sham normoxia treatment, and viability was determined using the resazurin assay. Neuronal viability was significantly reduced after OGD, and was further decreased by DIOA treatment applied during OGD (p < 0.01) and by gabazine applied after OGD (p < 0.05). Bumetanide treatment during OGD increased viability (p < 0.05), while isoguvacine applied either during or after OGD did not influence viability. Our data suggests that NKCC1 and KCC2 function has an important impact on neuronal viability during the acute ischemic episode, while the GABAA receptor plays a role during the subsequent recovery period. These findings suggest that pharmacological modulation of transmembrane chloride transport could be a promising approach during stroke and highlight the importance of the timing of treatment application in relation to ischemia-reoxygenation.

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats.

BACKGROUND: High-fat diet (HFD) is a detrimental habit with harmful systemic consequences, including low-grade, long-lasting inflammation. During pregnancy, HFD can induce developmental changes. Moreover, HFD-related maternal obesity might enhance the risk of peripartum complications including hypoxic-ischemic encephalopathy secondary to perinatal asphyxia (PA). OBJECTIVES: Following our previous results showing that PA increases neuroinflammation and neuronal injury in the immature hippocampus and modifies hippocampal epigenetic programming, we further aimed to establish the impact of maternal HFD on offspring hippocampus response to PA. METHODS: We assessed hippocampal tumor necrosis factor alpha (TNFα), interleukin 1 beta -(IL-1b) and S-100B protein (S-100B), 24-48 h after PA exposure in postnatal day 6 Wistar rats, whose mothers received either the standard diet or HFD. The expression of small non-coding microRNA species miR124, miR132, miR134, miR146, and miR15a, as epigenetic markers for the maternal dietary influence on immature hippocampus response after PA, was determined 24 h after asphyxia exposure. Metabolic activity was measured using resazurin test in hippocampal cell suspension obtained 24 h after PA. RESULTS: Our results indicate that maternal HFD additionally increases hippocampal TNFα, IL-1b, and S-100B after PA. Also, PA associated with maternal HFD induces miR124 upregulation and miR132 downregulation relative to PA only. Metabolic activity was increased in hippocampal cells from pups whose mothers received HFD. CONCLUSION: HFD increases the PA-induced neuroinflammation and neuronal injury, and epigenetically influences homeostatic synaptic plasticity and neuronal tolerance to asphyxia, processes associated with a higher hippocampal cellular metabolism.