Small Shifts in Craniotomy Position in the Lateral Fluid Percussion Injury Model Are Associated with Differential Lesion Development

Abstract

Previous studies have shown that location and direction of injury may affect outcome in experimental models of traumatic brain injury. Significant variability in outcome data has also been noted in studies using the lateral fluid percussion brain injury model (FPI) in rats. In recent studies from our laboratory, we observed considerable variability in localization and severity of tissue damage as a function of small changes in craniotomy position. To further address this issue, we examined the relationship between craniotomy position and brain lesion size/location in rats subjected to moderate FPI (2.28 +/- 0.18 atmospheres). With placement of a 5-mm craniotomy adjacent to the sagittal suture, there was both ipsilateral and contralateral damage as detected at 3 weeks posttrauma using T2-weighted magnetic resonance imaging (MRI). The MRI lesions were generally restricted to the hippocampus and subcortical layers. Shifting of the craniotomy site laterally was associated with increased ipsilateral tissue damage and a greater cortical component that correlated with distance from the sagittal suture. In contrast, the contralateral MRI lesion did not change significantly in size or location unless the center of the craniotomy was placed more than 3.5 mm from the sagittal suture, under which condition contralateral damage could no longer 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 during the lateral FPI model in rats. Addressing such potential variability is essential for studies that address either injury mechanisms or therapeutic treatments.

Experimental models of traumatic axonal injury

“…50,51 The craniotomy position also has an important influence on the extent of tissue injury produced in the FPI model. 52,53 The FPI device consists of a methacrylate cylindrical reservoir filled with sterile isotonic saline. One end of the reservoir includes a transducer connected to a tube that is attached through a plastic fitting to a cap cemented to the animals' skull.…”

Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences

“…Originally developed as a midline injury in cats [2] and rabbits [3], a lateral fluid percussion injury was used in rats [4], and further adapted for mice [5], now widely used given the utility of transgenic lines. Lateral fluid percussion injury produces a combined focal cortical contusion and diffuse subcortical neuronal injury in rats [6], the extent and location of which is subject to small changes in craniotomy position [7]. It is noteworthy that small alterations in craniotomy position in rats lead to differences in cognitive performance [8].…”

A behavioral and histological comparison of fluid percussion injury and controlled cortical impact injury to the rat sensorimotor cortex

“…[11] Additionally, it has been shown that any small shift in craniotomy location alters the neurological outcome, as well as the lesion size and location of the injury. [13]…”