Role of 5-HT in Cerebral Edema after Traumatic Brain Injury

Abstract

The pathogenesis of edema after traumatic brain injury is complex including the destruction of micro-vessels and alterations in microcirculation around the primary injury and leakage of plasma constituents into the tissue, due to permeability changes of the vessel walls. Many functional molecules like histamine, serotonin, arachidonic acid, prostaglandins and thromboxane have been shown to induce blood–brain barrier (BBB) disruption or cell swelling. It is believed that released 5-HT binds to 5-HT2 receptors stimulating cAMP and prostaglandins in vessels that cause more vesicular transport in endothelial cells leading to serum component’s extravasation. The additional amount of serotonin into the tissue due to injury maintains the state of increased vascular permeability that ultimately causes edema. Serotonin is clearly involved in early cytotoxic edema after TBI. Reduction of serotonin in the nervous tissue reduces swelling and the milder cell changes in the brain or spinal cord of traumatized rats. Inhibition of serotonin synthesis before closed head injury (CHI) in rat models or administration of serotonin antiserum after injury attenuates BBB disruption and brain edema volume swelling, and brain pathology. Maintaining low serotonin levels immediately after injury may show neuroprotection and combat various secondary outcomes that occur after traumatic brain injury.