Functional magnetic resonance imaging of the primary somatosensory cortex in piglets
Dartmouth–Hitchcock Medical Center, LEB, New Hampshire, United States Journal of Neurosurgery
(Impact Factor: 3.74).
05/2006; 104(4 Suppl):259-64. DOI: 10.3171/ped.2006.104.4.259
The piglet is an excellent model for the developing human brain, and has been used increasingly in various centers for studies of traumatic brain injury and other insults. Unlike rodent or primate models, however, there are few behavioral scales for the piglet, and the available ones are used to test general responsiveness rather than specific functional outcome. The differing behavioral repertoires of animals of different ages provide an additional challenge when age-dependent injury responses are compared. To overcome these experimental limitations of piglets in brain injury research, the authors developed a functional magnetic resonance (fMR) imaging paradigm that can be used to track recovery in the somatosensory cortex over time in anesthetized animals of different ages.
Fifteen fMR imaging studies in eight piglets were performed before and after scaled cortical impact injury to the primary somatosensory cortex subserving snout sensation. Specific anesthetic and imaging protocols enabled visualization of cortical activation, and comparison with somatosensory evoked potentials obtained before and after injury was obtained. A piglet brain template for group-level analysis of these data was constructed, similar to the fMR imaging techniques used in humans, to allow for group comparisons and longitudinal change analysis over time.
Loss of function in a specifically traumatized cortical region and its subsequent recovery over time can now be demonstrated visually by fMR imaging in the piglet. Besides its value in understanding intrinsic recovery mechanisms and plasticity at different ages, this functional outcome measure will enable the use of the piglet model in treatment trials specifically designed for the immature brain.
Available from: Andrew O. Koob
- "Studies have shown the activity of this area through functional magnetic resonance imaging (fMRI) (Grate et al., 2003; Duhaime et al., 2006). In addition to fMRI, sensory responses of the snout in the somatasensory cortex can be analyzed with electroencephalograph (EEG) and focal injury to the area abolishes EEG and fMRI activity when the snout is touched (Duhaime et al., 2006). These established models can be helpful for the discovery of effective treatments for head injury and the extent of cellular genesis after injury. "
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ABSTRACT: Because of the anatomical and developmental similarity of the piglet brain to the human brain we were interested in characterizing the areas of cellular genesis which occur postnatally to validate the model for subsequent neurobiological research. In this study, four piglets were injected with 5-bromodeoxyuridine (BrdU) at 6, 7 and 8 days of age. The animals were sacrificed at 13 days of age and the brains were analyzed to characterize areas of cellular genesis. BrdU was seen throughout the brain and found to be most abundant in the subventricular zone (SVZ); doublecortin (DCX) expressing cells were found throughout the white matter-with an extensive DCX network in the SVZ. Here we describe for the first time the use of immunohistochemistry for BrdU and DCX to study cellular genesis in the piglet brain.
International Journal of Developmental Neuroscience 11/2008; 26(6):641-6. DOI:10.1016/j.ijdevneu.2008.04.001 · 2.58 Impact Factor
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ABSTRACT: Large animal models have been used much less frequently than rodent models to study traumatic brain injury. However, large animal models offer distinct advantages in replicating specific mechanisms, morphology and maturational stages relevant to age-dependent injury responses. This paper reviews how each of these features is relevant in matching a model to a particular scientific question and discusses various scaling strategies, advantages and disadvantages of large animal models for studying traumatic brain injury in infants and children. Progress to date and future directions are outlined.
Developmental Neuroscience 02/2006; 28(4-5):380-7. DOI:10.1159/000094164 · 2.70 Impact Factor
Available from: reanimacao.com.br
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ABSTRACT: This review will update the reader on the most significant recent findings with regards to both the clinical research and basic science of pediatric traumatic brain injury.
The developing brain is not simply a smaller version of the mature brain. Studies have uncovered important distinctions of the younger brain after traumatic brain injury, including an increased propensity for apoptosis, age-dependent parameters for cerebral blood flow and metabolism, development-specific biomarkers, increased likelihood of early posttraumatic seizures, differential sensitivity to commonly used neuroactive medications and altered neuroplasticity during recovery from injury. Specifically, there is strong preclinical evidence for increased neuronal apoptosis in the developing brain being triggered by anesthetics and anticonvulsants, making it paramount that future studies more clearly delineate preferred agents and specific indications for use, incorporating long-term functional outcomes as well as short-term benefits. In addition, the young brain may actually benefit from therapeutic interventions that have been less effective following adult traumatic brain injury, such as decompressive craniectomy and hypothermia.
An increasing body of evidence demonstrates the importance of establishing age-dependent guidelines for physiological monitoring, pharmacological intervention, management of intracranial pressure and facilitating recovery of function.
Current Opinion in Critical Care 05/2007; 13(2):143-52. DOI:10.1097/MCC.0b013e32808255dc · 2.62 Impact Factor
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