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Biomechanics of traumatic brain injury: influences of the morphologic heterogeneities of the cerebral cortex.

ABSTRACT: Traumatic brain injury (TBI) can be caused by accidents and often leads to permanent health issues or even death. Brain injury criteria are used for assessing the probability of TBI, if a certain mechanical load is applied. The currently used injury criteria in the automotive industry are based on global head kinematics. New methods, based on finite element modeling, use brain injury criteria at lower scale levels, e.g., tissue-based injury criteria. However, most current computational head models lack the anatomical details of the cerebrum. To investigate the influence of the morphologic heterogeneities of the cerebral cortex, a numerical model of a representative part of the cerebral cortex with a detailed geometry has been developed. Several different geometries containing gyri and sulci have been developed for this model. Also, a homogeneous geometry has been made to analyze the relative importance of the heterogeneities. The loading conditions are based on a computational head model simulation. The results of this model indicate that the heterogeneities have an influence on the equivalent stress. The maximum equivalent stress in the heterogeneous models is increased by a factor of about 1.3-1.9 with respect to the homogeneous model, whereas the mean equivalent stress is increased by at most 10%. This implies that tissue-based injury criteria may not be accurately applied to most computational head models used nowadays, which do not account for sulci and gyri.

SUBMITTER: Cloots RJ

PROVIDER: S-EPMC2413127 | biostudies-other | 2008 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundTraumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent.ResultsAmong the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-delta and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, alpha-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen.ConclusionThe different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since trauma is a risk factor for development of neurodegenerative disease, this knowledge may also reduce late negative effects.

Project description:Few translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17 and PND35 rats (n = 75) received a mild to moderate midline fluid percussion injury or sham surgery. In three cortical regions [peri-injury, primary somatosensory barrel field (S1BF), perirhinal], we investigated the glial response relative to age-at-injury (PND17 or PND35), time post-injury (2 hours, 1 day, 7 days, 25 days, or 43 days), and post-natal age, such that rats injured at PND17 or PND35 were compared at the same post-natal-age (e.g., PND17 + 25D post-injury = PND42; PND35 + 7D post-injury = PND42). We measured Iba1 positive microglia cells (area, perimeter) and quantified their activation status using skeletal analysis (branch length/cell, mean processes/cell, cell abundance). GFAP expression was examined using immunohistochemistry and pixel analysis. Data were analyzed using Bayesian multivariate multi-level models. Independent of age-at-injury, TBI activated microglia (shorter branches, fewer processes) in the S1BF and perirhinal cortex with more microglia in all regions compared to uninjured shams. TBI-induced microglial activation (shorter branches) was sustained in the S1BF into early adulthood (PND60). Overall, PND17 injured rats had more microglial activation in the perirhinal cortex than PND35 injured rats. Activation was not confounded by age-dependent cell size changes, and microglial cell body sizes were similar between PND17 and PND35 rats. There were no differences in astrocyte GFAP expression. Increased microglial activation in PND17 brain-injured rats suggests that TBI upregulates the glial response at discrete stages of development. Age-at-injury and aging with an injury are translationally important because experiencing a TBI at an early age may trigger an exaggerated glial response.

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Biomechanics of traumatic brain injury: influences of the morphologic heterogeneities of the cerebral cortex.

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