Stroke is one of the main reasons of acquired epilepsy in adults. Little is known about the underlying pathomechanisms that occur during epileptogenesis, so between the transient hypoxia and the first late seizure.Some transcription factors drive gene-expression towards an epileptogenic phenotype through channelopathies, which may be acquired through brain insults, such as the T-type Ca2+ channel CaV3.2.Hypoxia-inducible factor 1α (HIF-1α) is quickly activated and can bind to the promoter of CaV3.2, potentially inducing an epileptogenic cascade in penumbra neurons.We used NS20Y cells and primary mouse cortical neurons, overexpressed HIF-1α (AAV-hSyn-HIF1A-GFP), and measured Cav3.2 levels by luciferase dual reporter assay or using the Cav3.2 core reporter unit controlling expression of a fluorescent reporter. To identify the effects of HIF-1α overexpression on the network activity of cortical neurons, microelectrode arrays (MEA) were performed.In both NS20Y cells and primary cortical neurons, we found a drastic upregulation of CaV3.2 expression upon overexpression of HIF-1α under normoxic conditions. In primary cortical neurons, MEA recordings showed that neurons transduced with HIF-1α developed an increased weighted-mean firing rate as well as higher numbers of network bursts compared to control neuronal populations.We provide first evidence that transient ischemia could trigger pro-epileptogenic processes, which could lead to chronic seizures after stroke. We could show that overexpression of HIF-1α not only leads to an upregulation of Cav3.2, but also causes network activity changes. Taken together, these results provide first insights into the molecular and electrophysiological mechanisms underlying the development of recurrent seizures after transient ischemia.