Increased hippocampal uptake of tumor necrosis factor alpha and behavioral changes in mice

Brain trauma may alter the function of the blood-brain barrier (BBB) and affect psychomotor activity. We have shown that the transport system for tumor necrosis factor alpha (TNF alpha) at the BBB undergoes regulatory changes after spinal cord injury. In this study, we show in CD1 mice that mild trauma by weight-drop to the right temporal region specifically increases the uptake of blood-borne TNF alpha. This increase, measured by use of radiolabeled murine TNF alpha, occurred only in the right hippocampus 24 h after injury and returned to normal at 1 week. There was no increase in the uptake of the vascular marker albumin at 1 h, 24 h, or 1 week postinjury, indicating that the BBB remained relatively intact. Human interleukin-1 beta, which does not cross the BBB by saturable transport, showed no significant changes in brain uptake after trauma. Therefore, the selective entry of TNF alpha in the injured right hippocampus may be explained by enhanced transport across the BBB. To explore the functional relevance of this transport regulation, we measured mouse behavior by the staircase test. The number of rearings, mainly reflective of exploratory behavior, decreased at 1 h and 1 day after injury but increased at 1 week after a 30-g weight-drop injury. The number of stairs ascended, mainly indicative of locomotor activity, was unchanged at all times tested. We conclude that mild, blunt brain trauma involving the hippocampus causes specific upregulation of TNF alpha transport and a selective change in exploratory behavior. Although no causal relationship can be established at this time, the behavioral changes might be related to the increased TNF alpha transport after trauma.