Fig. 1: Dynamic profiles of molecular and cellular changes following needle trauma.

Upon needle injection, the brain experiences physical damage, leading to the rupture of resident cells such as neurons, astrocytes, microglia, and oligodendrocytes. This rupture results from the impact of the needle, causing these cells to burst. Subsequently, the ruptured cells release damage-associated molecular patterns (DAMPs) rapidly, which affect neighboring cells and trigger the production and secretion of cytokines and chemokines due to activation. Among the cells sensing this response, neutrophils are quickly recruited to the damaged site, playing a pivotal role in promptly eliminating the debris. Concurrently, astrocytes and microglia become increasingly activated and migrate toward the damaged area over time. Approximately by the third day, peripheral monocytes infiltrate, and depending on the severity of the brain damage, T and B cells may also infiltrate, engaging in reparative functions. This sequence of inflammatory processes is crucial for the removal of cell debris resulting from needle trauma, facilitating essential steps for the repair and homeostasis of the damaged area. At the same time, however, this event appears to cause substantial damage and death to engrafted mDANs.