Breakdown of the blood-brain barrier after fluid percussive brain injury in the rat. Part 1: Distribution and time course of protein extravasation

Abstract

Experimental brain injury is associated with marked vasogenic edema, as evidenced by an increase in brain water content. This prominent and widespread response raises questions about the vulnerability of microvasculature in the brain to injury. In the present report we further characterize the vascular response by evaluating the integrity of the blood-brain barrier to circulating proteins. Vascular permeability to endogenous immunoglobulins (IgG) and to the protein horseradish peroxidase (HRP) was examined after a lateral, fluid percussive brain injury in the rat. In study 1 IgG was immunolocalized in brain sections 1-24 hr after injury. In studies 2 and 3 HRP was given intravenously either before impact (study 2) or 10 min before sacrifice (study 3). Permeability to this protein was assessed at 1-6 hr (study 2) or at 1-72 hr (study 3) after injury. In studies 1 and 2 the extravascular accumulation of proteins was evaluated. Pronounced abnormal permeability to IgG and HRP occurred within the first hour after injury and was widespread throughout both hemispheres. The intensity of immunostaining for IgG increased with time up to 24 hr after injury. In contrast, maximal extravascular accumulation of HRP occurred within the first hour after injury. In study 3 the time course for re-establishment of the blood-brain barrier to HRP was determined. Maximal permeability occurred at 1 hr after injury. At 24 hr abnormal permeability was restricted to the impact site and this area remained permeable up to 72 hr after injury. In summary this study demonstrates that breakdown of the blood-brain barrier to plasma proteins is a prominent feature of experimental brain injury. This abnormal permeability is characterized by its transient expression and widespread distribution. The time course for re-establishment of the blood-brain barrier to circulating proteins is most delayed at the impact site.