Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.

Stroke is one of the leading causes of death worldwide and currently only few therapeutic options are available. Stroke is a sexually dimorphic disease contributing to the difficulty in finding efficient treatments. Poststroke neuroinflammation is geared largely by brain microglia and infiltrating peripheral immune cells and largely contributes to sex differences in the outcome of stroke. Microglia, since very early in the development, are sexually divergent, imprinting specific sex-related features. The diversity in terms of microglial density, morphology, and transcriptomic and proteomic profiles between sexes remains in the adulthood and is likely to contribute to the observed sex-differences on the postischemic inflammation. The impact of sexual hormones is fundamental: changes in terms of risk and severity have been observed for females before and after menopause underlining the importance of altered circulating sexual hormones. Moreover, aging is a driving force for changes that interact with sex, shifting the inflammatory response in a sex-dependent manner. This review summarizes the present literature on sex differences in stroke-induced inflammatory responses, with the focus on different microglial responses along lifespan.