Development of a Model of Hemispheric Hypodensity (“Big Black Brain”)

Abstract

Subdural hematoma (SDH) is the most common finding after abusive head trauma (AHT). Hemispheric hypodensity (HH) is a radiological indicator of severe brain damage that encompasses multiple vascular territories, and may develop in the hemisphere(s) underlying the SDH. In some instances where the SDH is predominantly unilateral, the widespread damage is unilateral underlying the SDH. To date, no animal model has successfully replicated this pattern of injury. We combined escalating severities of the injuries and insults commonly associated with HH including SDH, impact, mass effect, seizures, apnea, and hypoventilation to create an experimental model of HH in piglets aged 1 week (comparable to human infants) to 1 month (comparable to human toddlers). Unilateral HH evolved over 24 h when kainic acid was applied ipsilateral to the SDH to induce seizures. Pathological examination revealed a hypoxic-ischemic injury-type pattern with vasogenic edema through much of the cortical ribbon with relative sparing of deep gray matter. The percentage of the hemisphere that was damaged was greater on the ipsilateral versus contralateral side and was positively correlated with SDH area and estimated seizure duration. Further studies are needed to parse out the pathophysiology of this injury and to determine if multiple injuries and insults act synergistically to induce a metabolic mismatch or if the mechanism of trauma induces severe seizures that drive this distinctive pattern of injury.

Big Black Brain Phenomenon: Understanding Clinicoradiological Dissociation in Non-Accidental Traumatic Brain Injury in Children

“…Infants are prone to a distinctive injury pattern of developing unilateral or bilateral hemispheric hypodensity (HH) or "big black brain," terms reflective of CT findings in the setting of acute SDH. HH is believed to reflect a decompensation of hemispheric cerebral perfusion/metabolic demand related to SDH and other stressors, including hypoventilation, hypoxia, and seizures or other electrophysiologic perturbations, although the exact pathophysiology is incompletely understood [2]. The visual tracking movements seen in our patient reflect a brain stem reflex to non-specific movement similar to the oculocephalic reflex.…”

The (Extracellular) Matrix Reloaded: Imaging Matrix Metalloproteinase Activity

“…It would be interesting to extend this study to look for common patterns of MMP activity in animal models of PTE, which more directly model human epilepsy. Furthermore, since ACPPs do not require genetic alterations to the species being studied, they could be applied to study PTE in large animals, 8 giving insight into the ECM remodeling that takes place following trauma in a gyrencephalic brain.…”

Abusive and Nonabusive Traumatic Brain Injury: Different Diseases, Not Just Different Intent

“…4 This finding comports with other evidence of AHT-specific patterns of inflammatory, ischemic, or excitotoxic secondary injury processes found in animal and imaging studies. [10][11][12] If further study confirms inflammatory processes particular to AHT, such information could improve both AHT recognition and our understanding of the processes of secondary injury; that is, when damage occurs after the initial trauma. Coupled with improved prevention, mitigation of secondary injuries is likely to be our most promising target for therapy.…”