Secondary insults worsen blood brain barrier dysfunction assessed by MRI in cerebral contusion.

Abstract

Understanding the cause of post-traumatic intracranial hypertension requires information about the pathophysiology of edema formation. Secondary insults are known to exacerbate edema formation following experimental contusion, however the influence of these insults on blood brain barrier (BBB) integrity is not known. This study non-invasively assesses the influence of hypoxia and hypotension on BBB permeability following experimental cortical contusion. Sprague-Dawley rats (350-380 g) were divided into three groups. Group A: (n = 3) Sham, Group B (n = 8) focal injury (controlled cortical impact 6.0 m/sec, 3 mm depth), Group C (n = 8), focal injury with secondary insult. Cortical BBB integrity was assessed four hours post-trauma using an i.v. bolus of 0.2 mmol/kg Gd-DTPA with serial T1 MR images, over 30 minutes. Absolute tissue concentrations of Gd were measured empirically using known references. The time course of accumulation was analyzed with respect to BBB permeability. BBB permeability was greatest in the site of contusion, and Gd accumulation was greatly enhanced by secondary insult (p < 0.01). Regions of lowest ADC and maximal swelling correlated with regions of maximal BBB permeability (p < 0.05). Secondary insults enhance BBB dysfunction in contusion. Positive relationships between low ADC, tissue swelling and BBB dysfunction suggest synergy between underlying cytotoxic swelling and BBB permeability in contusion. These data also suggest that restoration of BBB integrity after injury may be an energy dependent process. These findings have important implications for the pathophysiology of ICP elevations following cerebral contusion.