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 x 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 x 10(9)/L vs 1.471 +/- 0.322 x 10(9)/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 lCBF 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.

Acute Brain Injury Triggers MyD88-Dependent, TLR2/4-Independent Inflammatory Responses

“…The latter finding is compatible with several reports on lack of infarction size reduction through depletion of neutrophils or interference with neutrophil-endothelial interactions after physical brain injury. 80,81 Although the mechanism underlying the neuroprotective effect of MyD88 deficiency remains to be elucidated in detail, our data and those of others suggest involvement of the IL-1R-MyD88 pathway. We observed here that injury-induced up-regulation of IL-1␤ expression was abrogated in MyD88-deficient mice.…”

Neutrophils Promote Mononuclear Cell Infiltration During Viral-Induced Encephalitis

“…Inflammatory cell migration across the BBB is often associated with the loss of vascular integrity (33). Surprisingly, neutropenia greatly reduced infiltration of all inflammatory cells in addition to reducing loss of BBB integrity.…”

Cerebral Vascular and Metabolic Response to Sustained Systemic Inflammation in Ovine Traumatic Brain Injury

“…Cerebral inflammation is nowadays increasingly recognized as a key element in the pathogenesis of secondary tissue damage both in traumatic and ischemic brain injury (Danton and Dietrich, 2003;Morganti-Kossmann et al, 2001). After head trauma, leukocyte infiltration and proinflammatory cytokines are related to disturbances of cerebral blood flow (Siren et al, 2001;Uhl et al, 1994) as well as tissue injury and apoptosis (Fee et al, 2003), and may also contribute to blood-brain-barrier breakdown (Whalen et al, 1998). Less attention, however, has been paid to the cerebral pathophysiology associated with inflammatory processes of primarily systemic origin.…”