Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed experiments in Px1 ^−/− , Px2 ^−/− , and Px1 ^−/− Px2 ^−/− knockout mice. IL-1β release, channel function in astrocytes, and cortical spreading depolarization were not altered in Px1 ^−/− Px2 ^−/− mice, indicating that, in contrast to previous concepts, these processes occur normally in the absence of pannexin channels. However, ischemia-induced dye release from cortical neurons was lower, indicating that channel function in Px1 ^−/− Px2 ^−/− neurons was impaired. Furthermore, Px1 ^−/− Px2 ^−/− mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. In conclusion, our data demonstrate that Px1 and Px2 underlie channel function in neurons and contribute to ischemic brain damage.

Objectives: The aim of this ecological study was to investigate what the impact of digital learning due to the COVID-19 pandemic was on the burnout and overall mental health (MH) of medical students. Background: During the unprecedented era of the COVID-19 pandemic, the majority of countries worldwide adopted very strong measures. Universities closed their doors, and education continued through digital learning lectures. Methods: An anonymous questionnaire was administered to all 189 eligible candidates before and during the COVID-19 pandemic. Mental health was assessed via the MH domain of the 36-item Short Form Health Survey (SF-36) and burnout with the Maslach Burnout Inventory—Student Survey (MBI-SS). Results: The overall response rate was 81.5%. The overall burnout prevalence did not differ significantly between the two periods (pre-COVID-19 18.1% vs. COVID-19 18.2%). However, the burnout prevalence dropped significantly in year 4 (pre-COVID-19 40.7% vs. COVID-19 16.7%, p = 0.011), whereas it increased significantly in year 6 (pre-COVID-19 27.6% vs. COVID-19 50%, p = 0.01). When looking at each MBI-SS dimension separately, we found that emotional exhaustion decreased significantly in year 4 but increased in year 6, and cynicism increased in all years. The overall MH deteriorated significantly between the two periods (pre-COVID-19 58.8 ± 21.6 vs. COVID-19 48.3 ± 23, p < 0.001). Conclusions: Digital learning in medical studies carries significant risks. Not only does the MH deteriorate, but cynicism levels also increase. Emotional exhaustion was found to increase particularly in final year students, who struggle with the lack of clinical experience just before they start working as qualified junior doctors.

Neuronal apoptosis contributes to ischemic brain damage and neurodegenerative disorders. Key regulators of neuronal apoptosis are the transcription factor NF-κB and the MAP kinases p38/MAPK and JNK, which share a common upstream activator, the mitogen-activated protein kinase kinase kinase (MAP3K) TGFβ-activated kinase 1 (TAK1). Here we investigate the function of TAK1 in ischemia-induced neuronal apoptosis. In primary cortical neurons, TAK1 was activated by oxygen glucose deprivation (OGD), an in vitro model of cerebral ischemia. We found that short-term inhibition of TAK1 protected against OGD in vitro and reduced the infarct volume after middle cerebral artery occlusion in vivo. Prolonged inhibition or deletion of the TAK1 gene in neurons was, however, not protective. Short-term, but not prolonged inhibition of TAK1 interfered with the activation of p38/MAPK and JNK by OGD, the induction of the pro-oxidative genes Cox-2, Nox-2, and p40^phox, and the formation of superoxide. We found that prolonged TAK1 inhibition upregulated another MAP3K, apoptosis signal-regulating kinase-1, which is able to compensate for TAK1 inhibition. Our study demonstrates that TAK1 is a central target for short-term inhibition of key signaling pathways and neuroprotection in cerebral ischemia.