Journal of neurotrauma
-
Journal of neurotrauma · Nov 2010
Early and sustained increase in the expression of hippocampal IGF-1, but not EPO, in a developmental rodent model of traumatic brain injury.
Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). ⋯ EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.
-
Journal of neurotrauma · Nov 2010
Spinal cord blood flow and blood vessel permeability measured by dynamic computed tomography imaging in rats after localized delivery of fibroblast growth factor.
Following spinal cord injury, profound vascular changes lead to ischemia and hypoxia of spinal cord tissue. Since fibroblast growth factor 2 (FGF2) has angiogenic effects, its delivery to the injured spinal cord may attenuate the tissue damage associated with ischemia. To limit systemic mitogenic effects, FGF2 was delivered to the spinal cord via a gel of hyaluronan and methylcellulose (HAMC) injected into the intrathecal space, and compared to controls receiving HAMC alone and artificial cerebrospinal fluid (aCSF) alone. ⋯ Laminin staining for blood vessels showed a qualitative increase in vessel density after 7 days when FGF2 was locally delivered. Additionally, permeability stains showed that FGF2 moderately decreased permeability at 7 days post-injury. These data demonstrate that localized delivery of FGF2 improves spinal cord hemodynamics following injury, and that perfusion CT is an important technique to serially measure these parameters in small animal models of spinal cord injury.
-
Journal of neurotrauma · Oct 2010
Longitudinal characterization of motor and cognitive deficits in a model of penetrating ballistic-like brain injury.
Traumatic brain injury (TBI) produces a wide range of motor and cognitive changes. While some neurological symptoms may respond to therapeutic intervention during the initial recovery period, others may persist for many years after the initial insult, and often have a devastating impact on quality of life for the TBI victim. ⋯ The results showed that PBBI produced consistent and significant (1) neurological deficits (neuroscore examination: 30 min to 10 weeks post-PBBI), (2) sensorimotor dysfunction in the contralateral forelimb (forelimb asymmetry task: 7 and 21 days), (3) motor dysfunction (balance beam task: 3-7 days; and fixed-speed rotarod task: 3-28 days), and (4) spatial learning deficits in the Morris water maze (MWM) task out to 10 weeks post-injury. Overall, the results of this study demonstrate that PBBI produces enduring motor and cognitive deficits, and identifies the optimal task and testing parameters for facilitating longitudinal screening of promising therapeutic interventions in this brain injury model.
-
Journal of neurotrauma · Oct 2010
In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury.
Comprehensive in vivo longitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. ⋯ Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI.
-
Journal of neurotrauma · Oct 2010
Effects of traumatic brain injury of different severities on emotional, cognitive, and oxidative stress-related parameters in mice.
Cognitive deficits and psychiatric disorders are significant sequelae of traumatic brain injury (TBI). Animal models have been widely employed in TBI research, but few studies have addressed the effects of experimental TBI of different severities on emotional and cognitive parameters. In this study, mice were subjected to weight-drop TBI to induce mild, intermediate, or severe TBI. ⋯ Intermediate and severe TBI caused extensive macroscopic and microscopic brain damage, while mild TBI typically had no histological abnormalities. Moreover, a significant increase in TBARS in the ipsilateral cortex and GPx in the ipsilateral hippocampus was observed at 24 h and 14 days, respectively, following intermediate TBI. The current experimental TBI model induced emotional and cognitive changes comparable to sequelae seen in human TBI, and it might therefore represent a useful approach to the study of mechanisms of and new treatments for TBI and related disorders.