Leukotriene production by human glia

Abstract

Elevated intracranial pressure and acute cerebrovascular changes following head injury remain the principle challenge in the management of traumatic brain injury. Recent work has demonstrated that leukotrienes can induce increases in blood brain barrier permeability and alter cerebrovascular dynamics. We investigated whether human astroglia in culture: 1. generate specific leukotrienes; 2. how they metabolize leukotrienes, and; 3. if astroglia generate leukotrienes in response to barotraumatic injury. Human astroglial cultures established from normal human brain obtained at surgery were exposed to either ionophore, exogenous 3H-LTC4, or barotraumatic injury. Supernatants were assayed for specific leukotrienes by one of three methods: HPLC, radioimmunoassay, or enzyme-immunoassay. Glial cells exposed to exogenous LTC4 metabolized nearly all of the LTC4 to LTD4 and LTE4 within 20 minutes. Glial cells stimulated with ionophore produced mostly LTC4 at five minutes after stimulation and LTD4 and LTE4 at fifteen minutes after stimulation. Glial cells subject to barotraumatic injury produced LTC4 in concentrations of 40-200 pg/ml 15 minutes after injury. These results demonstrate that human astroglial cells are capable of rapidly generating and degrading LTC4 and this capability of glial cells may play an important role in the pathophysiology of cerebrovascular changes following head injury.