Experimental Acute Subdural Hematoma in Infant Piglets

Shaver, Ellen G.; Duhaime, Ann‐Christine; Curtis, Mark J.; Gennarelli, L; Barrett, Ronald

doi:10.1159/000121109

Cited by 56 publications

(36 citation statements)

References 15 publications

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“…26,37,46 Contusion injury, diffuse axonal injury, acute subdural hematoma, and epidural hematoma have been characterized in pigs or piglets. 7,32,33,44,46 The piglet ages selected for this study were based on parallels between pig and human development. These three time points were chosen to help answer the question of when maturational differences occur that might be relevant to injury response; it is not clear from clinical experience whether only infants show different injury patterns or whether vulnerability changes in a continuum or in a step-wise manner.…”

Section: Discussionmentioning

confidence: 99%

Maturation-dependent response of the piglet brain to scaled cortical impact

Duhaime¹,

Margulies²,

Durham³

et al. 2000

Journal of Neurosurgery

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Object. The goal of this study was to investigate the relationship between maturational stage and the brain's response to mechanical trauma in a gyrencephalic model of focal brain injury. Age-dependent differences in injury response might explain certain unique clinical syndromes seen in infants and young children and would determine whether specific therapies might be particularly effective or even counterproductive at different ages.Methods. To deliver proportionally identical injury inputs to animals of different ages, the authors have developed a piglet model of focal contusion injury by using specific volumes of rapid cortical displacement that are precisely scaled to changes in size and dimensions of the growing brain. Using this model, the histological response to a scaled focal cortical impact was compared at 7 days after injury in piglets that were 5 days, 1 month, and 4 months of age at the time of trauma. Despite comparable injury inputs and stable physiological parameters, the percentage of hemisphere injured differed significantly among ages, with the youngest animals sustaining the smallest lesions (0.8%, 8.4%, and 21.5%, for 5-day-, 1-month-, and 4-month-old animals, respectively, p = 0.0018).Conclusions. These results demonstrate that, for this particular focal injury type and severity, vulnerability to mechanical trauma increases progressively during maturation. Because of its developmental and morphological similarity to the human brain, the piglet brain provides distinct advantages in modeling age-specific responses to mechanical trauma. Differences in pathways leading to cell death or repair may be relevant to designing therapies appropriate for patients of different ages.

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Section: Discussionmentioning

confidence: 99%

Maturation-dependent response of the piglet brain to scaled cortical impact

Duhaime¹,

Margulies²,

Durham³

et al. 2000

Journal of Neurosurgery

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146

120

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“…In our large-animal models of TBI, we have demonstrated that cortical impact alone 22,23 or SDH alone causes focal damage, 15 but not the extensive widespread acute hypoxic-ischemic type damage observed in HH. In immature rodents prior to 18 days of age, parental kainic acid (1-6 mg/kg) induced severe, generalized tonic-clonic seizures without any histopathological damage, and limbic seizures and ''red neurons,'' neuronal dropout, and a gliotic reaction and scarring at 18 days of age and thereafter.…”

Section: Discussionmentioning

confidence: 79%

“…In previous models of pediatric brain injury, we demonstrated that neither cortical impact 22,23 nor SDH 48 cause HH, but we have not yet tested the theory that HH could be due to seizures alone.…”

Section: Discussionmentioning

confidence: 84%

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

Costine-Bartell

McGuone

Price

et al. 2019

Journal of Neurotrauma

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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.

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“…9,10,30 To date, experimental models and clinical evidence have failed to fully explain the development of HH in association with subdural blood. Animal studies designed to mimic SDH in the immature brain, such as the subdural murine model, in which blood is injected over the cerebral convexity through a burr hole 31 or the cranial window infant piglet model, 32 have failed to lead to HH. Moreover, studies to recapitulate the possible mechanisms of AHT using rat 33 and piglet 34 shaking models have not shown HH.…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Hemispheric Hypodensity after Subdural Hematoma following Abusive Head Trauma in Children

Foster

Recker

Lee

et al. 2014

Journal of Neurotrauma

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Abusive head trauma (AHT) is a unique form of pediatric TBI with increased mortality and neurologic sequelae. Hemispheric hypodensity (HH) in association with subdural blood after AHT has been described. Though risk factors for HH are not understood, we hypothesized that risk factors could be identified. We retrospectively enrolled children under 5 years with TBI secondary to AHT (child advocacy diagnosis) who had undergone initial and interval brain imaging. Records were interrogated for prearrival and in-hospital physiologic and radiographic findings. HH was determined by a blinded observer. Twenty-four children were enrolled and 13 developed HH. HH was not significantly associated with age, initial Glascow Coma Scale, or mortality. Pediatric Intensity Level of Therapy (PILOT) scores ( p = 0.01) and daily maximal intracranial pressure (ICP max ; p = 0.037) were higher in HH. Hypoxia, hypotension, cardiopulmonary arrest, need for blood transfusion, and daily blood glucoses tended to be greater in HH. Whereas all children with HH had acute subdural hematoma (SBH), many children without HH also had subdural blood; the presence of skull fracture was more likely in the children who did not develop HH ( p = 0.04), but no other intracranial radiographic pattern of injury was associated with HH. Surgical intervention did not appear to protect against development of HH. A variety of insults associated with ischemia, including intracranial hypertension, ICP-directed therapies, hypoxia, hypotension, and cardiac arrest, occurred in the children who developed HH. Given the morbidity and mortality of this condition, larger studies to identify mechanisms leading to the development of HH and mitigating clinical approaches are warranted.

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Experimental Acute Subdural Hematoma in Infant Piglets

Cited by 56 publications

References 15 publications

Maturation-dependent response of the piglet brain to scaled cortical impact

Maturation-dependent response of the piglet brain to scaled cortical impact

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

Factors Associated with Hemispheric Hypodensity after Subdural Hematoma following Abusive Head Trauma in Children

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