Immunomorphological sequelae of severe brain injury induced by fluid-percussion in juvenile pigs - effects of mild hypothermia

Severe traumatic brain injury (TBI) often leads to a bad outcome with consi derable neurological deficits. Secondary brain injuries due to a rise of in tracranial pressure (ICP) and global hypoxia-ischemia are critical and may be reduced in extent by mild hypothermia. A porcine animal model was used t o study the effect of severe TBI, induced by fluid percussion (FP; 3.5 +/-0 .3 atm) in combination with a secondary insult, i.e., temporary blood loss with hypovolemic hypotension. Six-week-old juvenile pigs were subjected to this kind of severe TBI; one group was then submitted to moderate hypotherm ia at 32 degreesC for 6 h, starting 1 h after brain injury. Animals were ki lled after 24 h. TBI and hypothermia-associated alterations in the brains w ere investigated by immunohistochemistry with antibodies against microtubul e-associated protein 2 (MAP-2) and beta -amyloid precursor protein (beta AP P). In addition, DNA fragmentation was investigated by the terminal deoxynu cleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method. Seven of the 13 normothermic TBI animals developed a secondary increase in ICP (TBI-NT-ICP) after an interval of several hours. None of the animals i n the hypothermic trauma (TBI-HT) group exhibited a secondary ICP increase, indicating a protective effect of the treatment. TBI-HT animals showed sig nificantly higher levels of MAP-2 immunoreactivity, lower levels of beta AP P immunoreactivity and less DNA fragmentation than the TBI-NT-ICP animals. Differences between the TBI-HT group and normothermic animals without an IC P increase (TBI-NT) were less marked. A considerable decrease in MAP-2 outs ide the site of TBI-FP administration was seen only in the TBI-NT-ICP anima ls. MAP-2 immunohistochemistry was thus a reliable marker of diffuse brain damage. Axonal injury was present in all TBI groups, indicating its special significance in neurotrauma. Thus, severe TBI caused by FP, combined with temporary blood loss, consistently produced traumatic axonal injury and foc al brain damage. Mild hypothermia was able to prevent a secondary increase in ICP and its sequelae of diffuse hypoxic-ischemic brain injury. However, hypothermia did not afford protection from traumatic axonal injury.