title: Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia.
abstract: We investigated the temporal and regional profile of blood-brain barrier (BBB) permeability to both large and small molecules after moderate fluid percussion (FP) brain injury in rats and determined the effects of post-traumatic modest hypothermia (33 degrees C/4 h) on these vascular perturbations. The visible tracers biotin-dextrin-amine 3000 (BDA-3K, 3 kDa) and horseradish peroxidase (HRP, 44 kDa) were injected intravenously at 4 h or 3 or 7 days post-TBI. At 30 min after the tracer infusion, both small and large molecular weight tracers were detected in the contusion area as well as remote regions adjacent to the injury epicenter in both cortical and hippocampal structures. In areas adjacent to the contusion site, increased permeability to the small molecular weight tracer (BDA-3K) was evident at 4 h post-TBI and remained visible after 7 days survival. In contrast, the larger tracer molecule (HRP) appeared in these remote areas at acute permeable sites but was not detected at later post-traumatic time periods. A regionally specific relationship was documented at 3 days between the late-occurring permeability changes observed with BDA-3K and the accumulation of CD68-positive macrophages. Mild hypothermia initiated 30 min after TBI reduced permeability to both large and small tracers and the infiltration of CD68-positive cells. These results indicate that moderate brain injury produces temperature-sensitive acute, as well as more long-lasting vascular perturbations associated with secondary injury mechanisms.
authors: Department of Neurological Surgery, Neurotrauma Research Center, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: George
authors: G
authors: Lotocki
authors: Juan Pablo
authors: JP
authors: de Rivero Vaccari
authors: Enrique R
authors: ER
authors: Perez
authors: Juliana
authors: J
authors: Sanchez-Molano
authors: Ofelia
authors: O
authors: Furones-Alonso
authors: Helen M
authors: HM
authors: Bramlett
authors: W Dalton
authors: WD
authors: Dietrich
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002452:Cell Count; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley