Antibodies to Serotonin Attenuate Closed Head Injury Induced Blood-Brain Barrier Disruption and Brain Pathology

摘要

Closed head injury (CHI) often results in profound brain swelling and instant death of the victims due to compression of the vital centers. However, the neurochemical basis of edema formation in CHI is still obscure. Previous studies from our laboratory show that blockade of serotonin synthesis prior to CHI in a rat model attenuates brain edema, indicating a prominent role for serotonin in head injury. Thus, neutralization of endogenous serotonin activity and/or blocking of its receptors will induce neuroprotection in CHI. Since serotonin has more than 14 receptors and selective serotonin antagonists are still not available, we used serotonin antiserum to neutralize its in vivo effects before or after CHI in a rat model. CHI was produced by an impact of 0.224 N on the right parietal skull bone under Equithesin anesthesia by dropping a weight of 114.6g from a height of 20 cm through a guide tube. This concussive brain injury resulted in blood-brain barrier (BBB) disruption, brain edema formation, and volume swelling at 5 h that were most pronounced in the contralateral cerebral hemisphere. The plasma and brain serotonin levels were increased several-fold at this time. Intracere-broventricular administration of serotonin antiserum (1:20, monoclonal) into the left lateral cerebral ventricle (30 μL in PBS) 30 min before or 30 min (but not 60 min) after CHI significantly attenuated BBB disruption, brain edema formation, volume swelling, and brain pathology. The plasma and brain serotonin levels continued to remain high. These observations are the first to suggest that antiserum to serotonin when administered into the CSF during the early phase of CHI are capable of inducing neuroprotection.