Biology subjects

Hofmeijer, J.

Publications and source records attributed to Hofmeijer, J..

2 recordsLinked to original sources

bioRxiv2024

Does sex matter in neurons response to hypoxic stress?

BackgroundStroke exhibits significant sex differences in incidence, response to treatment and outcome. Preclinical studies suggest that hormones, particularly estrogens, are key to differential sensitivity, as female neurons demonstrate enhanced resilience compared to males in both in vivo and in vitro models. This study investigates whether these sex-specific differences in neuronal vulnerability extend to the ischemic penumbra and explores the effects of estrogens under such conditions. MethodsPrimary cortical neuronal networks were generated from male and female new-born Wistar rats and cultured on micro-electrode arrays or glass coverslips. Male and female networks were subjected to hypoxic conditions, followed by a recovery phase, with or without exogenous estrogen treatment. Electrophysiological activity, including spikes and bursts, was monitored and analyzed. Apoptosis was assessed through immunocytochemistry, focusing on caspase-dependent and apoptosis inducing factor (AIF)-dependent pathways. ResultsUnder hypoxic conditions, male and female neuronal networks exhibited a similar decrease in firing and network burst rates, with an associated increase in network burst durations. Estrogen treatment altered these dynamics, leading to increased network burst rates and decreased network burst duration for both sexes. During recovery, no significant differences were observed between estrogen-treated and untreated networks. Immunocyto-chemistry revealed that estrogen significantly influenced caspase-dependent apoptosis, and to a lesser extent AIF-dependent apoptosis. ConclusionsIn our model of the ischemic penumbra, sex-dependent differences in neuronal responses to hypoxic injury are primarily driven by estrogen, rather than intrinsic neuronal characteristics. Although our electrophysiological data demonstrated that estrogen influenced network activity, it did not offer long-term neuroprotection after hypoxia.

neuroscience↗

bioRxiv2022

Preservation of thalamocortical circuitry is essential for good recovery in comatose survivors of cardiac arrest

Continuous EEG monitoring contributes to prediction of neurological outcome in comatose cardiac arrest survivors. While the phenomenology of EEG abnormalities in postanoxic encephalopathy is well-known, the pathophysiology, especially the presumed role of selective synaptic failure is less understood. To further this understanding, we estimate biophysical model parameters from the EEG power spectra from individual patients with a good or poor recovery from a postanoxic encephalopathy. This biophysical model includes intracortical, intrathalamic, and corticothalamic synaptic strengths, as well as synaptic time constants and axonal conduction delays. We used continuous EEG measurements from hundred comatose patients recorded during the first 48 hours post-cardiac arrest, fifty with a poor neurological outcome (Cerebral Performance Category (CPC=5)) and fifty with a good neurological outcome (CPC=1). We only included patients that developed (dis-) continuous EEG activity within 48 hours post-cardiac arrest. For patients with a good outcome, we observed an initial relative excitation in the corticothalamic loop and corticothalamic propagation that subsequently evolved towards values observed in healthy controls. For patients with a poor outcome, we observed an initial increase in the cortical excitation-inhibition ratio, increased relative inhibition in the corticothalamic loop, delayed corticothalamic propagation of neuronal activity, and severely prolonged synaptic time constants, that did not return to physiological values. We conclude that the abnormal EEG evolution in patients with a poor neurological recovery after cardiac arrest may result from persistent and selective synaptic failure that includes corticothalamic circuitry, but also delayed corticothalamic propagation.

neuroscience↗