title: Immunomorphological sequelae of severe brain injury induced by fluid-percussion in juvenile pigs--effects of mild hypothermia.
abstract: Severe traumatic brain injury (TBI) often leads to a bad outcome with considerable neurological deficits. Secondary brain injuries due to a rise of intracranial pressure (ICP) and global hypoxia-ischemia are critical and may be reduced in extent by mild hypothermia. A porcine animal model was used to 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 hypothermia at 32 degrees C for 6 h, starting 1 h after brain injury. Animals were killed after 24 h. TBI and hypothermia-associated alterations in the brains were investigated by immunohistochemistry with antibodies against microtubule-associated protein 2 (MAP-2) and beta-amyloid precursor protein (betaAPP). In addition, DNA fragmentation was investigated by the terminal deoxynucleotidyltransferase-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 in the hypothermic trauma (TBI-HT) group exhibited a secondary ICP increase, indicating a protective effect of the treatment. TBI-HT animals showed significantly higher levels of MAP-2 immunoreactivity, lower levels of betaAPP immunoreactivity and less DNA fragmentation than the TBI-NT-ICP animals. Differences between the TBI-HT group and normothermic animals without an ICP increase (TBI-NT) were less marked. A considerable decrease in MAP-2 outside the site of TBI-FP administration was seen only in the TBI-NT-ICP animals. 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 focal 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.
authors.affiliation: Institute of Pathology (Neuropathology), Friedrich Schiller University, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brodhun
authors.forename: H
authors.initials: H
authors.lastname: Fritz
authors.forename: B
authors.initials: B
authors.lastname: Walter
authors.forename: I
authors.initials: I
authors.lastname: Antonow-Schlorke
authors.forename: K
authors.initials: K
authors.lastname: Reinhart
authors.forename: U
authors.initials: U
authors.lastname: Zwiener
authors.forename: R
authors.initials: R
authors.lastname: Bauer
authors.forename: S
authors.initials: S
authors.lastname: Patt
mesh_terms: D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D053938:DNA Fragmentation / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced; D020896:Hypovolemia / Q000503:physiopathology / Q000628:therapy*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology / Q000628:therapy*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011312:Pressure / Q000009:adverse effects; D013552:Swine
chemical_list: D016564:Amyloid beta-Protein Precursor; D008869:Microtubule-Associated Proteins