095. Greater matrix metalloproteinase activity and vasogenic edema in toddlers than infants in a gyrencephalic, multi-factorial, severe TBI model.

Authors: Amy Baohan, MD

Brain injury due to abusive head trauma (AHT) is the leading cause of trauma-related death in children under the age of four. Hemispheric hypodensity (HH) is a radiographic pattern of diffuse hemispheric atrophy and hypodensity seen on CT associated with subdural hematoma (SDH) following AHT in infants and toddlers, encompassing multiple vascular territories. If the SDH is unilateral, the HH is unilateral with sparing of the contralateral hemisphere. However, little is understood about the underlying pathophysiology.Methods: In our model of HH, consisting of cortical impact, midline shift, SDH with subarachnoid hemorrhage (SAH), traumatic seizures with brief apnea and hypoventilation, “toddlers” (30-day old piglets) have extensive hypoxic-ischemic type injury with vasogenic edema in the hemisphere underlying the SDH/SAH whereas “infants” (7-day old piglets) have less damage spread over both hemispheres.
Seizure duration is positively correlated with area of tissue damage in “toddlers” but not “infants”. Here, we examine the involvement of matrix metalloproteinases (MMPs) that could explain the age-dependent pattern and response to seizure. “Toddlers” displayed widespread MMP-9 expression, restricted to the hemisphere underlying the SDH/SAH while “infants” had less MMP-9 expression spread over both hemispheres. MMP-9 protein abundance via Western blot in the cortex rostral to the cortical impact was increased at 1hr post-injury in “toddlers” but not in “infants”. There was a significant time by age interaction with cortical expression of MMP-3 increasing over 24hrs in “toddlers” but decreasing over time in “infants”. Similarly, using gelatin zymography on peripheral plasma, MMP-9 activity increased over time in “toddlers”, but decreased over time in “infants”. MMP-2 activity increased in “toddlers” but not “infants”.
“Infants” may be resistant to the effects of traumatic seizure by downregulating MMPs, thus reducing spread of tissue damage. Further work is needed to determine if MMPs can be targets of intervention to improve long-term outcome.