Effects of Neutropenia on Edema,Histology,and Cerebral Blood Flow After Traumatic Brain Injury in Rats

Abstract

Neutrophils accumulate during the acute inflammatory response to brain injury, but their role in the injury process remains controversial. We tested the hypothesis that neutrophils contribute to cerebral edema, tissue injury, and disturbed cerebral blood flow (CBF) (hyperemia or ischemia) during the first 24 h after traumatic brain injury. Wistar rats (n = 51) were injected with either vinblastine sulfate to induce neutropenia or the saline vehicle. Five days later, under halothane anesthesia, right hemispheric trauma was produced by weight drop (10 g × 5 cm) onto exposed dura. At 24 h after trauma, brain water (wet-dry weight), traumatic infarct size (percent of hemispheric section infarcted), or local CBF (lCBF,¹⁴C-iodoantipyrine autoradiography) was assessed. Vinblastine treatment produced profound neutropenia on the day of trauma (absolute neutrophil count 0.024 ± 0.008 × 10⁹/L vs 1.471 ± 0.322 × 10⁹/L,p < 0.05 in neutropenic vs saline, respectively, mean ± SEM). Neutropenia did not reduce the development of brain edema in the injured hemisphere (brain water 82.38 ± 0.29% vs 82.73 ± 0.37% in neutropenic and saline, respectively, mean ± SEM) or traumatic infarct size (34.5 ± 3.3% vs 33.2 ± 2.1 % in neutropenic vs saline respectively). In contrast, neutropenic rats exhibited 52 %, 41%, and 57% reductions in 1CBF in the frontal cortex, parietal cortex, and amygdala, respectively, of the injured hemisphere 24 h after trauma (all p < 0.05 vs nonneutropenic controls). These data suggest that neutrophils and the acute inflammatory process contribute to the level of CBF observed 24 h after trauma, but effects on edema or early posttraumatic infarct size could not be demonstrated.