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Clinical studies suggest that increased cerebral blood flow (CBF), or hyperemia, after traumatic brain injury (TBI) is commonly found in children and young adults, but is less often found in adults older than 40 years. However, whether posttraumatic cerebral hyperemia is truly an age-related phenomenon has not been proven. Using a model of focal percussive TBI, we hypothesized that (1) local CBF (ICBF) is increased by 24 after injury, and (2) the magnitude of the ICBF increase is age-related and is greatest in immature rats. Wistar rats that were immature (3.5-4.5 weeks), mature (2-3 months), and aged (14.5-15.5 months) were anesthetized and ventilated. TBI was produced by dropping a weight on the exposed right parietal cortex. LCBF was determined by [(14)C]iodoan-tipyrine autoradiography at 24 h posttrauma in all three age groups, at 48 h posttrauma in immature and mature rats, and at 7 days posttrauma in mature rats. In all age groups, low ICBF (<50 mL 100 g(-1) min(-1)) was present in the area of impact at all times studied. At 24 h, hyperemia was observed (vs. corresponding regions of age-matched control rats) in immature and mature rats (7/17 and 5/17 regions, respectively, both p < 0.05), but not in aged rats. Comparisons of ICBF between the three age groups revealed a hyperemic response in the peritrauma region in immature rats. Hyperemia persisted to 48 h in both immature and mature rats (2 and 7 of 17 structures with increased ICBF in immature and mature rats, respectively, both p < .05). By 7 days posttrauma no regions of increased ICBF were found. Posttraumatic hyperemia appears to be an age-dependent phenomenon. These results suggest possible age-related differences in vasoreactivity or regional metabolism after TBI.

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.

Clinical studies suggest that children respond to head injury with more pronounced cerebral edema and hyperemia than do adults. We hypothesized that these age-related differences could be demonstrated in an animal model. Anesthetized and ventilated mature (2-3 months) and immature (3.5-4.5 weeks) male Wistar rats were traumatized by weight drop onto the exposed right parietal cortex. Trauma severity was adjusted to keep the ratio of force to brain weight constant. This resulted in an energy delivered to the brain of about 9 x 10(3) ergs.mm-2.g-1 brain in both age groups. Percent right hemispheric brain water (%RBW) was measured at 2, 24, 48, and 168 h posttrauma. Infarct area, intracranial pressure (ICP), and 14C-iodoantipyrine autoradiographic local cerebral blood flow (ICBF) were measured at 2 h or 24 h posttrauma. In mature rats, %RBW was unchanged at 2 h, but increased at 24 and 48 h (both p < 0.05). In immature rats, %RBW increased at 2 h and remained elevated at 24 and 48 h (all p < 0.05). Traumatic infarct area as a percent of hemispheric area at 24 h did not differ between age groups. In mature rats, at 2 h posttrauma ICBF was reduced (p < 0.05) in 16 of 17 regions but in only 4 of 17 regions in immature rats. ICBF as a percent of age-matched control values showed a greater reduction in mature vs immature rats in 9 of 16 regions (p < 0.05). ICP increased at 24 h posttrauma in both age groups. In immature rats posttrauma, brain water increased earlier and cerebral hypoperfusion was less marked than in mature rats.

Polymorphonuclear leukocytes (PMN) are implicated in the pathogenesis of traumatic brain injury. We tested the following hypotheses: (1) leukocyte accumulation is present in brain tissue 24 h posttrauma, (2) leukocyte accumulation represents PMN, and (3) prior systemic PMN depletion attenuates brain tissue PMN accumulation. Trauma was induced in exposed right parietal cortex by weightdrop in anesthetized Wistar rats (n = 24). Of the traumatized rats, 12 were PMN-depleted with vinblastine sulfate i.v. Controls were 12 normal rats and 5 sham-operated rats (craniotomy). Sections of traumatized and contralateral hemispheres were analyzed for myeloperoxidase (MPO) activity. Brain MPO activity was increased fivefold at 24 h posttrauma, but only in the traumatized hemisphere (0.448 +/- 0.133 U/g vs 0.090 +/- 0.022 U/g in trauma vs normal, respectively, p < 0.05, mean +/- SEM). PMN depletion attenuated this increase in MPO activity and decreased circulating PMN counts (0.07 +/- 0.032 x 10(9)/L vs 0.894 +/- 0.294 x 10(9)/L PMN-depleted-trauma vs trauma rats, respectively, p < 0.05). Leukocyte accumulation in the brain posttrauma was confirmed by MPO assay. Inhibition of MPO activity in the PMN-depleted group and the specificity of vinblastine treatment for depletion of circulating PMN suggest that leukocyte accumulation in the brain at 24 h posttrauma is largely due to PMN.