Deciphering microglial activation and neuronal apoptosis post‑traumatic brain injury: The role of TYROBP in inflammation regulation networks.

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro‑arrays, high‑throughput RNA sequencing and single‑cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase‑binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF‑α), vascular endothelial growth factor and transforming growth factor β via the NF‑κB pathway. Cells co‑culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non‑contact mechanisms. Activated microglia secrete cytokines, including TNF‑α, CXCL‑8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.