A MODEL OF DIFFUSE TRAUMATIC BRAIN INJURY IN THE IMMATURE RAT

Diffuse cerebral swelling after severe traumatic brain injury (TBI) de velops more commonly in children than adults; however, models of diffu se brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a rec ently described closed head injury model for adult rats. A total of 10 5 Sprague-Dawley immature rats (17 days old; average weight 38.5 +/- 5 .46 g) were subjected to he:td impact using variable weights (0 g (sha m), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neu rological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period afte r severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurolog ical recovery was complete in the sham-injured animals (11 rats) by 4. 1 +/- 0.23 minutes (mean +/- standard error of the mean), but was dela yed in both moderately injured (MI) (75 g/2 m; Il rats) (14.97 +/- 3.9 9 minutes) and ST (20.57 +/- 1.31 minutes (p < 0.05)) rats. In the fir st 24 hours, the sham-injured animals were more active than the injure d ones as reflected by a greater net weight gain: 2.9 +/- 1.0 g, 1.2 /- 1.6 g, and -0.6 +/- 2.1 g in sham-injured, MI, and SI animals, resp ectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 +/- 0.7 minutes and 1.27 +/- 0.53 minutes in MI and SI groups, respective ly), which either resolved or deteriorated to death. Intubation and as sisted ventilation in animals with SI for 9.57 +/- 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonin tubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Ot her injuries included neuronal death in the deep nuclei, bilateral dis ruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventric ulomegaly. Following a diffuse TBI in immature rats, SI produced a mor tality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maint aining the height of the weight drop but varying the weights. Weight l oss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilato ry support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.