Posttreatment with high-dose albumin reduces histopathological damage and improves neurological deficit following fluid percussion brain injury in rats

We have recently shown that high-dose human serum albumin (HSA) therapy con fers marked histological protection in experimental middle cerebral artery occlusion. Thus, the purpose of this study was to determine whether treatme nt with high-dose HSA would protect in a rat model of traumatic brain injur y (TBI). Twenty-four hours prior to TBI, the fluid percussion interface was positioned parasagittally over the right cerebral cortex. On the following day, fasted rats were anesthetized with 3% halothane, 70% nitrous oxide, a nd 30% oxygen and received right parieto-occipital parasagittal fluid-percu ssion injury (1.5-2.0 atm). Cranial and rectal temperatures were monitored throughout the experiment and held at normothermic levels (36.5-37.5 degree s C) by a warming lamp above the animal's head. The agent (25% human serum albumin, HSA) or vehicle (sodium chloride 0.9%) was administered i.v. (1% o f body weight) 15 min after trauma. Behavioral function was evaluated in al l rats before and after TBI (at 2 h, 24 h, 48 h, 72 h, and 7 days). Neurolo gical function was graded on a scale of 0-12 (normal score 0; maximal score = 12). Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas in the superficial, middle and deep layers of cortex and in the underlying fimbria were measure d. HSA significantly improved the neurological score compared to saline at 24 h, 72 h, and 7 days after TBI (6.0 +/- 0.6 [albumin] versus 8.4 +/- 0.5 [saline]; 3.6 +/- 0.7 versus 6.8 +/- 1.0; and 2.6 +/- 0.6 versus 5.7 +/- 0. 8, respectively; p < 0.05). HSA therapy also significantly reduced total co ntusion area (0.89 +/- 0.2 versus 1.82 +/- 0.3 mm(2); p = 0.02). Our findin gs document that high-concentration albumin therapy instituted 15 min after trauma significantly improves the neurological score and reduces histologi cal damage. We believe that this pharmacological agent may have promising p otential for the clinical treatment of brain injury.