Depletion of neutrophils reduces neuronal degeneration and inflammatory responses induced by quinolinic acid in vivo.

The use of anti-neutrophil serum (anti-PMN) to induce neutropenia has been assessed for neuroprotection, modulation of microgliosis and astrogliosis, effects on oxidative stress, and intactness of blood-brain barrier (BBB) following injection of the excitotoxin quinolinic acid (QUIN) into rat striatum. At 1 day following QUIN injection, considerable striatal neurodegeneration was measured (Fluoro-Jade B marker). At this time, marked microgliosis (OX-42 marker) and astrogliosis (GFAP marker) were evident in QUIN-injected striatum. Treatment of QUIN-injected animals with anti-PMN protected neurons (48% reduction of striatal neuron loss) and inhibited microgliosis (61% reduction) and astrogliosis (43% reduction) compared with QUIN injection alone. Anti-PMN treatment was effective in decreasing levels of superoxide anions (by 42%) compared with QUIN alone; in addition, expressions of the neutrophil enzyme myeloperoxidase and the neutrophil oxidant 3-chlorotyrosine were markedly reduced (by 79 and 72%, respectively) with neutrophil depletion. QUIN-induced leakiness in BBB was indicated by elevated striatal levels of the blood protein fibrinogen, a result confirmed using Evans blue dye; anti-PMN was effective in reducing BBB permeability. Measurements from QUIN-injected animals directly confirmed anti-PMN efficacy in diminishing numbers of circulating neutrophils. Longer term neuroprotection and reduced microgliosis were also observed at 7 days post-injection of anti-PMN; at this time, anti-PMN-treated rats also demonstrated an improved apomorphine-induced rotational performance. We conclude that anti-PMN treatment could serve as a novel strategy to prevent leakiness to BBB, reduce gliosis, and protect striatal neurons in excitotoxin-injected brain.