Small shifts in craniotomy position in the lateral fluid percussion injurymodel are associated with differential lesion development

Previous studies have shown that location and direction of injury may affec t outcome in experimental models of traumatic brain injury. Significant var iability in outcome data has also been noted in studies using the lateral f luid percussion brain injury model (FPI) in rats. In recent studies from ou r laboratory, we observed considerable variability in localization and seve rity of tissue damage as a function of small changes in craniotomy position . To further address this issue, we examined the relationship between crani otomy position and brain lesion size/location in rats subjected to moderate FPI (2.28 +/- 0.18 atmospheres). With placement of a 5-mm craniotomy adjac ent to the sagittal suture, there was both ipsilateral and contralateral da mage as detected at 3 weeks posttrauma using T-2-weighted magnetic resonanc e imaging (MRI). The MRI lesions were generally restricted to the hippocamp us and subcortical layers. Shifting of the craniotomy site laterally was as sociated with increased ipsilateral tissue damage and a greater cortical co mponent that correlated with distance from the sagittal suture. In contrast , the contralateral MRI lesion did not change significantly in size or loca tion unless the center of the craniotomy was placed more than 3.5 mm from t he sagittal suture, under which condition contralateral damage could no lon ger be detected. Ipsilateral tissue damage as determined from the MRI scans was linearly correlated to motor outcome but not with cognitive outcome as assessed by the Morris Water Maze. We conclude that craniotomy position is critical in determining extent and location of tissue injury produced duri ng the lateral FPI model in rats. Addressing such potential variability is essential for studies that address either injury mechanisms or therapeutic treatments.