Following injury, astrocytes undergo major alterations in morphology and gene expression, leading to the acquisition of distinct “reactivity” states that play important roles in brain tissue repair. Evidence indicates that these cellular states are also marked by rewiring of mitochondrial energy metabolism, i.e. the central hub for cellular energy metabolism and metabolic signaling. However, how such mitochondrial responses are regulated and how they may influence astrocyte reactivity remains unclear. Our prior research unveiled temporal and region-specific morphological changes in astrocytic mitochondrial networks, delineating distinct reactivity states following acute injury. Namely, astrocytes positioned in the lesion penumbra displayed elongated mitochondria, while those within the pro-inflammatory lesion core exhibited pronounced mitochondrial fragmentation. Notably, we observed that fragmentation in these astrocytes was reversed upon resolution of inflammation, suggesting mitochondrial dynamics to regulate astrocyte function during reactivity. Accordingly, we recently showed that, by regulating mitochondrial-ER contact sites and calcium dynamics, mitochondrial fusion promotes the formation of stable perivascular mitochondrial domains that facilitate vascular remodeling. In contrast, little is known about the role of mitochondrial fission during the acute phase after injury. To impair mitochondrial fission, we conditionally ablated the astrocytic dynamin-related protein Drp1. This manipulation led to an intensified inflammation in the injured area, marked by an enlarged Gfap+ penumbra and robust microglial reactivity. Remarkably, Drp1-deficient astrocytes within the lesion core (but not penumbra) exhibited swollen mitochondria with loss of cristae, indicating that Drp1 activity is needed to preserve mitochondrial quality control in response to inflammation.