Early Onset of Rapid Lesion Growth in an Acute Subdural Hematoma Model in Rats

Abstract

Objective: Acute subdural hematoma (ASDH) leads to the highest mortality rates of all head injuries with secondary brain damage playing a pivotal role in terms of morbidity and mortality. In patients with ASDH, a delay in surgery leads to disproportional mortality. The benefit of (very) early therapy is therefore, a target of ongoing research. As the process of delayed brain damage in ASDH has not yet been described, this study therefore aimed to examine secondary lesion growth in an experimental rat model of ASDH to define the ideal timing for testing potential neuroprotective therapies.

Methods: Cerebral blood flow was monitored during ASDH induction with 300 μl of autologous blood. Lesion growth was characterized using Hematoxylin-Eosin- , Cresyl-Violet-, and Fluoro-Jade B-staining for early signs of neuronal degeneration. Histological evaluations were performed between 15 minutes and 24 hours after ASDH.

Results: There was a significant reduction of cerebral blood flow after ASDH. Fluoro-Jade B-positive cells were visible 15 minutes after ASDH in the lesioned hemisphere. Nonlinear growth of lesion volume from 3.7 ± 0.4 mm³ to 17.5 ± 0.6 mm³ was observed at 24 hours in Hematoxylin-Eosin-staining.

Conclusions: The most damage develops between 15 minutes and 1 hour and again between 2 and 6 hours after ASDH. The time course of lesion growth supports the approach of early surgery for patients. It furthermore constitutes a basis for further ASDH research with more clearly defined time windows for therapy in animal models.

Keywords: Acute subdural hematoma; Cerebral blood flow; Rat; Secondary brain damage; Traumatic brain injury.