Research Article
Mast Cell Activation, Neuroinflammation, and Tight Junction Protein Derangement in Acute Traumatic Brain Injury
Figure 9
Schematic representation of mast cell activation in neuroinflammation, BBB disruption, and neuronal death in closed-head acute TBI brain. Neurotrauma/TBI can cause primary damage to neurovascular and gliovascular units in the brain with subsequent neuroimmune and neuroinflammatory responses. This leads to the activation of immune cells, including microglia, astrocytes, and mast cells in the brain. Mast cell activation causes degranulation and release of prestored and preactivated mediators such as histamine, proteases, and TNF-α followed by newly synthesized cytokines, chemokines, and neurotoxic mediators that can act on glial cells and neurons. Subsequently, peripheral immune as well as inflammatory cells can infiltrate the region of injury in the brain due to the BBB breach. CCL2 released from mast cells and brain cells induces the infiltration of inflammatory cells. Activated glial cells release neuroinflammatory mediators that further activate glial cells, neurons, and mast cells in a vicious fashion and induce PAR-2 and VEGFR2 expression and BBB breach with decreased tight junction protein such as claudin 5 and ZO-1 and its derangements. This continuous process can cause and upregulate neuroinflammation and neuronal death and secondary brain damage after TBI.