In-depth characterization of a long-term, resuscitated model of acute subdural hematoma–induced brain injury

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OBJECTIVE

Acute subdural hematoma (ASDH) is a leading entity in brain injury. Rodent models mostly lack standard intensive care, while large animal models frequently are only short term. Therefore, the authors developed a long-term, resuscitated porcine model of ASDH-induced brain injury and report their findings.

METHODS

Anesthetized, mechanically ventilated, and instrumented pigs with human-like coagulation underwent subdural injection of 20 mL of autologous blood and subsequent observation for 54 hours. Continuous bilateral multimodal brain monitoring (intracranial pressure [ICP], cerebral perfusion pressure [CPP], partial pressure of oxygen in brain tissue [PbtO2], and brain temperature) was combined with intermittent neurological assessment (veterinary modified Glasgow Coma Scale [MGCS]), microdialysis, and measurement of plasma protein S100β, GFAP, neuron-specific enolase [NSE], nitrite+nitrate, and isoprostanes. Fluid resuscitation and continuous intravenous norepinephrine were targeted to maintain CPP at pre-ASDH levels. Immediately postmortem, the brains were taken for macroscopic and histological evaluation, immunohistochemical analysis for nitrotyrosine formation, albumin extravasation, NADPH oxidase 2 (NOX2) and GFAP expression, and quantification of tissue mitochondrial respiration.

RESULTS

Nine of 11 pigs survived the complete observation period. While ICP significantly increased after ASDH induction, CPP, PbtO2, and the MGCS score remained unaffected. Blood S100β levels significantly fell over time, whereas GFAP, NSE, nitrite+nitrate, and isoprostane concentrations were unaltered. Immunohistochemistry showed nitrotyrosine formation, albumin extravasation, NOX2 expression, fibrillary astrogliosis, and microglial activation.

CONCLUSIONS

The authors describe a clinically relevant, long-term, resuscitated porcine model of ASDH-induced brain injury. Despite the morphological injury, maintaining CPP and PbtO2 prevented serious neurological dysfunction. This model is suitable for studying therapeutic interventions during hemorrhage-induced acute brain injury with standard brain-targeted intensive care.

ABBREVIATIONS ASDH = acute subdural hematoma; CPP = cerebral perfusion pressure; ICP = intracranial pressure; I/E = inspiratory/expiratory; MGCS = modified Glasgow Coma Scale; NO = nitric oxide; NOX2 = NADPH oxidase 2; NSE = neuron-specific enolase; PbtO2 = partial pressure of oxygen in brain tissue; PEEP = positive end-expiratory pressure; ROS = reactive oxygen species.
Article Information

Contributor Notes

Correspondence Thomas Datzmann: University Hospital Ulm, Germany. thomas.datzmann@uni-ulm.de.INCLUDE WHEN CITING Published online December 20, 2019; DOI: 10.3171/2019.9.JNS191789.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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