THE ROLE OF NEUTROPHILS IN THE PRODUCTION OF HYPOXIC-ISCHEMIC BRAIN INJURY IN THE NEONATAL RAT

Neutrophils contribute to ischemic brain injury in adult animals. The role of neutrophils in perinatal hypoxic-ischemic (HI) brain injury is unknown. Allopurinol reduces neutrophil accumulation after tissue isc hemia and is protective against HI brain injury. This study was design ed to investigate how neutrophils contribute to perinatal hypoxic isch emic brain injury and how neutropenia compared with allopurinol in its neuroprotective effects. A HI insult was produced in the right cerebr al hemisphere of 7-d-old rats by right common carotid artery ligation and systemic hypoxia. Half the rats were rendered neutropenic with an anti-neutrophil serum (ANS). At 15 min of recovery from hypoxia, half the neutropenic and nonneutropenic rats received allopurinol (135 mg/k g, s.c.). The protective effect of the four treatment combinations was determined on brain swelling at 42 h of recovery. Neutropenia reduced brain swelling by about 70%, p < 0.01. Allopurinol alone produced sim ilar protection so that the relatively small number of animals studied did not permit assessment of an additive effect. Neutrophil accumulat ion in cerebral hemispheres was measured by myeloperoxidase (MPO) acti vity assay and by neutrophil counts in 6-mu m sections stained by MPO and ANS immunostaining. MPO activity peaked between 4 and 8 h of recov ery in both hemispheres. Hemispheric neutrophil counts peaked at the e nd of the HI insult and again at 18 h of recovery. Neutrophils were st ained within blood vessels and did not infiltrate the injured brain be fore infarction had occurred. We conclude that neutrophils contribute to HI brain injury in the neonate and that neutrophil depletion before the insult is neuroprotective.