Evidence for Impaired Plasticity after Traumatic Brain Injury in the Developing Brain

Abstract

The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating. We investigated the altered cortical plasticity 2-3 weeks after injury in a pediatric rat model of TBI. Significant decreases in neurophysiological responses across the depth of the noninjured, primary somatosensory cortex (S1) in TBI rats, compared to age-matched controls, were detected with electrophysiological measurements of multi-unit activity (86.4% decrease), local field potential (75.3% decrease), and functional magnetic resonance imaging (77.6% decrease). Because the corpus callosum is a clinically important white matter tract that was shown to be consistently involved in post-traumatic axonal injury, we investigated its anatomical and functional characteristics after TBI. Indeed, corpus callosum abnormalities in TBI rats were detected with diffusion tensor imaging (9.3% decrease in fractional anisotropy) and histopathological analysis (14% myelination volume decreases). Whole-cell patch clamp recordings further revealed that TBI results in significant decreases in spontaneous firing rate (57% decrease) and the potential to induce long-term potentiation in neurons located in layer V of the noninjured S1 by stimulation of the corpus callosum (82% decrease). The results suggest that post-TBI plasticity can translate into inappropriate neuronal connections and dramatic changes in the function of neuronal networks.

Diffusion MRI and the detection of alterations following traumatic brain injury

“…For example, while reduced axial diffusivity was reported to acutely follow CCI in the presence of axonal damage without myelin changes, a second study in the same model found that weeks after injury, when demyelination became evident, reduced anisotropy was no longer accompanied by reduced axial diffusivity but, instead, by increased radial diffusivity. This is supported by similar findings of increased radial diffusivity in a model with demyelination without axonal damage (Sun et al, 2006) as well as subsequent studies demonstrating DTI changes primarily in anisotropy with abnormal myelin staining (Budde et al, 2011;Jiang et al, 2011;Li et al, 2014). Notably, changes in myelination and myelinated fibers may influence anisotropy differently depending on the tissue investigated.…”

“…For instance, observations in a model of focal cortical ischemia (Pierpaoli et al, 1993) have demonstrated increased diffusivity in nonischemic brain regions with edema adjacent to regions of decreased diffusivity where ischemic damage was later confirmed by histology. The implication of this for TBI research is that acutely increased diffusivity may indicate brain regions that undergo edema without cellular disruption, and possibly these areas will not progress to degenerative outcomes, while regions with acutely decreased diffusivity are more likely to have metabolic or Sato et al, 2001;Chen et al, 2003;Coleman, 2005;Stoica & Faden, 2010Assaf et al, 1997Van Putten et al, 2005;Immonen et al, 2009;Laitinen et al, 2015 axonal injury axon morphology changes including beading and varicosities reduction in anisotropy and reduction in diffusion, especially in the axial direction Johnson et al, 2013Budde et al, 2009;Jiang et al, 2011;Li et al, 2011;Bennett et al, 2012; van de Looij et al, 2012 neural plasticity sprouting, arborization increased number of coherent processes and new collaterals increased anisotropy and/or changed orientation Bach-y-Rita, 2003;Yiu & He, 2006;Werner & Stevens, 2015;Meaney & Smith, 2015Kharatishvili et al, 2007Hutchinson et al, 2012;Sierra et al, 2015 Oligodendrocytes demyelination direct damage, chronic pathology degenerating or lost decreased anisotropy Armstrong et al, 2016Jiang et al, 2011Budde et al, 2011;Li et al, 2014;Mac Donald, Dikranian, Song, et al, 2007 myelination repair remyelination regenerating normalized anisotropy…”

“…This is consistent with findings in a study of isolated axonal injury found to be related to decreased FA and axial diffusivity (Budde, Xie, Cross, & Song, 2009). In addition, numerous subsequent experimental TBI studies of CCI (Budde, Janes, Gold, Turtzo, & Frank, 2011;Davoodi-Bojd et al, 2014;Jiang et al, 2011;Li et al, 2014;Wang et al, 2013;Zhuo et al, 2012), closed head injury (CHI) (Bennett, Mac Donald, & Brody, 2012;Li, Li, Feng, & Gu, 2011;van de Looij et al, 2012), and blast (Budde et al, 2013;Calabrese et al, 2014) have been able to detect histologically verified axonal pathology using dMRI approaches.…”

Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms

“…Similarly, loss of Gabrb3 gene signaling is associated with deficits in sensory processing [90]. Post-TBI changes in plasticity can also lead to sensory processing deficits [91]. The sensory processing deficits observed following TBI are statistically different compared to the normal range seen in noninjured children [92].…”

Elucidating Mechanisms of Neurobehavioral Dysfunction in a Rodent Model of Traumatic Brain Injury

“…Histopathology including profound neuronal injury and neuroinflammation has been demonstrated in rodent models of bTBI (de Lanerolle et al, 2011;Abdul-Muneer et al, 2013). Furthermore, bTBI has been suggested to result in suppression of synaptic plasticity in rat hippocampus (Miyazaki et al, 1992;Li et al, 2013a). Moreover, common biochemical and molecular mechanisms of brain injury have been demonstrated in a variety of bTBI models (Goldstein et al, 2012;Kochanek et al, 2013;Sosa et al, 2013;Turner et al, 2013b).…”