Early polymorphonuclear leukocyte accumulation correlates with the development of posttraumatic cerebral edema in rats.

To evaluate the role of polymorphonuclear leukocytes (PMNs) in the development of posttraumatic cerebral edema, we quantitatively assessed the time course and magnitude of PMN accumulation and its relationship to cerebral edema formation after cerebral trauma in 78 rats. 111In-labeled PMN accumulation was measured in 26 rats in the first 8 h after right hemispheric percussive cerebral trauma or a sham control condition. 51Cr-labeled erythrocyte accumulation was measured simultaneously in 22 rats to assess the contribution of expansion of blood volume to early posttraumatic PMN accumulation. Edema formation [right-left (R-L) hemispheric difference in percent brain water], R-L hemispheric labeled-PMN accumulation, and blood volume index-adjusted PMN accumulation were measured between 0-2 h and 4-8 h posttrauma. PMN accumulation was elevated markedly in the first 2 h posttrauma compared with values in sham controls (13.45 +/- 2.53 vs -0.03 +/- 0.31, p less than 0.01) but not when adjusted for blood volume index (BVI), suggesting that PMN accumulation in the first 2 h posttrauma was due to expansion of blood volume. Between 4 and 8 h posttrauma, however, both total (2.56 +/- 0.82 vs -0.29 +/- 0.52) and BVI-adjusted (8.78 +/- 3.97 vs -0.48 +/- 0.79) PMN accumulation were elevated (p less than 0.05) compared with sham. Brain edema and total PMN accumulation were significantly correlated at both 2 h and 8 h posttrauma (r2 = 0.77, p less than 0.001, and r2 = 0.69, p less than 0.002, respectively), but a significant correlation between edema and BVI-adjusted PMN accumulation was observed only at 8 h posttrauma (r2 = 0.96, p less than 0.001). These data show that PMN accumulation after traumatic brain injury occurs with an initial phase explained by an increase in blood volume in the first 2 h posttrauma followed by a subsequent acute inflammatory phase. The significant correlation between PMN accumulation and the development of cerebral edema is the first quantitative relationship demonstrated between PMN accumulation and a relevant pathophysiological variable. A causal role for PMNs in the genesis of posttraumatic cerebral edema has yet to be proved.