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

Abstract

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. Cerebral blood flow was monitored during ASDH induction with 300μl 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 15minutes and 24hours after ASDH. There was a significant reduction of cerebral blood flow after ASDH. Fluoro-Jade B-positive cells were visible 15minutes after ASDH in the lesioned hemisphere. Nonlinear growth of lesion volume from 3.7±0.4mm3 to 17.5±0.6mm3 was observed at 24hours in Hematoxylin-Eosin-staining. The most damage develops between 15minutes and 1hour and again between 2 and 6hours 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.