Inflammation impairs hippocampal neurogenesis in the adult brain. This study demonstrates that lipopolysaccharide-induced inflammation, which activates microglia in the region where new neurons are generated, significantly reduces basal hippocampal neurogenesis in rats. The increased neurogenesis following a brain injury is also reduced when associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. Systemic administration of minocycline, which inhibits microglia activation, restores neurogenesis suppressed by inflammation. These findings suggest that activated microglia may contribute to cognitive dysfunction in aging, dementia, epilepsy, and other brain inflammatory conditions. In the adult mammalian brain, neural progenitor cells in the subgranular zone (SGZ) of the dentate gyrus (DG) generate new neurons daily. These neurons integrate into existing neuronal circuits and may play a role in memory formation and mood regulation. Impairment of hippocampal neurogenesis is linked to cognitive decline in aging, Alzheimer's disease, and major depression. Brain inflammation is involved in the pathogenesis of chronic neurodegenerative disorders like Alzheimer's and Parkinson's disease. Inflammation activates microglia, which produce proinflammatory factors. Acute brain insults, such as stroke and status epilepticus (SE), are also linked to inflammation, which contributes to neuropathological events. These insults trigger increased neurogenesis in the SGZ. However, after severe SE, there is an 80% loss of newly formed dentate neurons, suggesting that the inflammatory response is detrimental to hippocampal neurogenesis. The study shows that microglia activation associated with inflammation impairs both basal and insult-induced hippocampal neurogenesis. Systemic administration of minocycline, which inhibits microglia activation, is effective in restoring neurogenesis suppressed by inflammation. The data suggest that activated microglia may suppress hippocampal neurogenesis, contributing to cognitive dysfunction in various conditions involving brain inflammation. The findings highlight the importance of anti-inflammatory treatments in improving neuronal replacement in neurodegenerative disorders.Inflammation impairs hippocampal neurogenesis in the adult brain. This study demonstrates that lipopolysaccharide-induced inflammation, which activates microglia in the region where new neurons are generated, significantly reduces basal hippocampal neurogenesis in rats. The increased neurogenesis following a brain injury is also reduced when associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. Systemic administration of minocycline, which inhibits microglia activation, restores neurogenesis suppressed by inflammation. These findings suggest that activated microglia may contribute to cognitive dysfunction in aging, dementia, epilepsy, and other brain inflammatory conditions. In the adult mammalian brain, neural progenitor cells in the subgranular zone (SGZ) of the dentate gyrus (DG) generate new neurons daily. These neurons integrate into existing neuronal circuits and may play a role in memory formation and mood regulation. Impairment of hippocampal neurogenesis is linked to cognitive decline in aging, Alzheimer's disease, and major depression. Brain inflammation is involved in the pathogenesis of chronic neurodegenerative disorders like Alzheimer's and Parkinson's disease. Inflammation activates microglia, which produce proinflammatory factors. Acute brain insults, such as stroke and status epilepticus (SE), are also linked to inflammation, which contributes to neuropathological events. These insults trigger increased neurogenesis in the SGZ. However, after severe SE, there is an 80% loss of newly formed dentate neurons, suggesting that the inflammatory response is detrimental to hippocampal neurogenesis. The study shows that microglia activation associated with inflammation impairs both basal and insult-induced hippocampal neurogenesis. Systemic administration of minocycline, which inhibits microglia activation, is effective in restoring neurogenesis suppressed by inflammation. The data suggest that activated microglia may suppress hippocampal neurogenesis, contributing to cognitive dysfunction in various conditions involving brain inflammation. The findings highlight the importance of anti-inflammatory treatments in improving neuronal replacement in neurodegenerative disorders.