Neuroinflammation and M2 microglia: the good, the bad, and the inflamed Microglia, the resident immune cells of the central nervous system (CNS), have long been studied for their role in maintaining brain homeostasis. Recent research has revealed that microglia can exist in multiple activation states, including classical (M1) and alternative (M2) activation. While M1 microglia are involved in pro-inflammatory responses, M2 microglia are associated with anti-inflammatory functions, tissue repair, and debris clearance. This review discusses the various activation states of microglia, their functional relevance in both acute and chronic CNS diseases, and the potential therapeutic applications of M2 microglial polarization. Microglia were first identified in the 19th century and were initially thought to be passive cells. However, modern research has shown that microglia are highly dynamic and can respond to various stimuli, including pathogens and damage-associated molecular patterns (DAMPs). In response to these stimuli, microglia can transition between M1 and M2 activation states. M1 microglia produce inflammatory cytokines and reactive oxygen species, while M2 microglia produce anti-inflammatory cytokines and are involved in tissue repair. The activation of microglia is influenced by various factors, including cytokines such as IL-4 and IL-10, which promote M2 activation. In contrast, pro-inflammatory cytokines like IFNγ and TNFα promote M1 activation. The balance between these activation states is crucial for maintaining CNS homeostasis. However, in neurodegenerative diseases such as Alzheimer's and multiple sclerosis, an imbalance in microglial activation can lead to chronic inflammation and tissue damage. M2 microglia have been shown to play a beneficial role in various CNS diseases, including spinal cord injury, traumatic brain injury, and stroke. For example, M2 microglia can promote tissue repair, reduce inflammation, and enhance neurogenesis. However, the effectiveness of M2 microglia in these contexts is still being studied, and there are concerns about the applicability of peripheral macrophage polarization models to the CNS. In Alzheimer's disease, microglial activation is a key factor in the progression of the disease. Aβ accumulation can trigger microglial activation, leading to chronic inflammation and neurodegeneration. However, M2 microglia have the potential to clear Aβ and reduce inflammation. The use of therapeutic agents such as glatiramer acetate, bexarotene, and PPARγ agonists has shown promise in modulating microglial activation and reducing disease severity. In conclusion, microglia play a critical role in maintaining CNS homeostasis and can exist in multiple activation states. The balance between M1 and M2 activation is essential for proper CNS function. Understanding the mechanisms of microglial activation and identifying therapeutic targets for modNeuroinflammation and M2 microglia: the good, the bad, and the inflamed Microglia, the resident immune cells of the central nervous system (CNS), have long been studied for their role in maintaining brain homeostasis. Recent research has revealed that microglia can exist in multiple activation states, including classical (M1) and alternative (M2) activation. While M1 microglia are involved in pro-inflammatory responses, M2 microglia are associated with anti-inflammatory functions, tissue repair, and debris clearance. This review discusses the various activation states of microglia, their functional relevance in both acute and chronic CNS diseases, and the potential therapeutic applications of M2 microglial polarization. Microglia were first identified in the 19th century and were initially thought to be passive cells. However, modern research has shown that microglia are highly dynamic and can respond to various stimuli, including pathogens and damage-associated molecular patterns (DAMPs). In response to these stimuli, microglia can transition between M1 and M2 activation states. M1 microglia produce inflammatory cytokines and reactive oxygen species, while M2 microglia produce anti-inflammatory cytokines and are involved in tissue repair. The activation of microglia is influenced by various factors, including cytokines such as IL-4 and IL-10, which promote M2 activation. In contrast, pro-inflammatory cytokines like IFNγ and TNFα promote M1 activation. The balance between these activation states is crucial for maintaining CNS homeostasis. However, in neurodegenerative diseases such as Alzheimer's and multiple sclerosis, an imbalance in microglial activation can lead to chronic inflammation and tissue damage. M2 microglia have been shown to play a beneficial role in various CNS diseases, including spinal cord injury, traumatic brain injury, and stroke. For example, M2 microglia can promote tissue repair, reduce inflammation, and enhance neurogenesis. However, the effectiveness of M2 microglia in these contexts is still being studied, and there are concerns about the applicability of peripheral macrophage polarization models to the CNS. In Alzheimer's disease, microglial activation is a key factor in the progression of the disease. Aβ accumulation can trigger microglial activation, leading to chronic inflammation and neurodegeneration. However, M2 microglia have the potential to clear Aβ and reduce inflammation. The use of therapeutic agents such as glatiramer acetate, bexarotene, and PPARγ agonists has shown promise in modulating microglial activation and reducing disease severity. In conclusion, microglia play a critical role in maintaining CNS homeostasis and can exist in multiple activation states. The balance between M1 and M2 activation is essential for proper CNS function. Understanding the mechanisms of microglial activation and identifying therapeutic targets for mod