TY - JOUR

T1 - Small shifts in craniotomy position in the lateral fluid percussion injury model are associated with differential lesion development

AU - Vink, R

AU - Mullins, P G

AU - Temple, M D

AU - Bao, W

AU - Faden, A I

PY - 2004/7/8

Y1 - 2004/7/8

N2 - 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.

AB - 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.

KW - Animals

KW - Behavior, Animal

KW - Brain

KW - Brain Injuries

KW - Craniotomy

KW - Disease Models, Animal

KW - Magnetic Resonance Imaging

KW - Male

KW - Maze Learning

KW - Rats

KW - Rats, Sprague-Dawley

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1089/089771501316919201

DO - 10.1089/089771501316919201

M3 - Article

C2 - 11526990

VL - 18

SP - 839

EP - 847

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 8

ER -