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.

Figures

FIG. 1.

Decreases in stimulus-evoked electrophysiology responses in the noninjured S1 in TBI rats 2 weeks after injury. (A) Cresyl violet histology sections of the damaged left somatosensory cortex. (B) An illustration of the axial array microelectrode that was centered at the noninjured S1 (bregma 0), contralateral to the injury. (C) Poststimulus time histograms of representative control and TBI rats show a decrease in the number of MUA responses across all S1 layers. Green arrows on the time axis represent forepaw stimulus onset. (D) Local field potential maps of representative control and TBI rats show a decrease in amplitude across S1 depth. Green arrows on time axis represent stimulus onset. TBI, traumatic brain injury; MUA, multi-unit activity. Color image is available online at www.liebertpub.com/neu

FIG. 2.

Decreases in BOLD fMRI responses in the noninjured S1 in TBI rats 2 weeks after injury. (A) Representative BOLD fMRI Z-maps (p<0.05) obtained from control (top) and TBI (bottom) rats are overlaid on the anatomical images. The noninjured S1 in TBI rat showed less BOLD fMRI activation extent in response to the contralateral forepaw (FP) stimulation, as compared to the control rat. The injured S1 in the TBI rat showed no BOLD fMRI responses induced by contralateral FP stimulation. The cortical damage resulting from TBI can be clearly visualized in the left hemisphere. (B) Group averaged fMRI Z-maps (p<0.05) obtained from control (n=5) and TBI (n=5) rats. (C) Average time course of the BOLD fMRI percentage changes (±standard error of the mean) in response induced by contralateral FP stimulation in TBI (n=5) and control (n=5) rats. The orange bar illustrates the stimulation duration. (D) The average number of activated pixels across the slices representing S1, within the S1 region, show a significant decrease in hemodynamic activity in TBI rats (n=5), compared to control (n=5; *p<0.05). TBI, traumatic brain injury; BOLD, blood-oxygen-level dependent; fMRI, functional magnetic resonance imaging. Color image is available online at www.liebertpub.com/neu

FIG. 3.

Corpus callosum abnormalities in TBI rats 2 weeks after injury. (A) Group averaged FA images at bregma 1.89 of control (n=5, top row) and TBI (n=5, bottom row) rats. Left: The corpus callosum area was segmented as marked in red. Right: Pseudo color maps of FA images show decreases in FA value in the corpus callosum of TBI rats, compared to controls. (B) Examples of the corpus callosum as segmented out of myelin-stained brain sections. Corpus callosum of a TBI rat at different sections within S1 (green) is superimposed on control (black). TBI, traumatic brain injury; FA, fractional anisotropy. Color image is available online at www.liebertpub.com/neu

FIG. 4.

Altered synaptic transmission in the noninjured S1 in TBI rats 2–3 weeks after injury. (A) The firing frequency of spontaneous miniature excitatory postsynaptic currents (mEPSC) was significantly decreased in TBI rats, compared to controls. Examples of traces of mEPSC from TBI and control rats are shown. (B) EPSCs were measured to evaluate the efficacy of neurotransmission between corpus callosum and layer V pyramidal neurons. Examples of the evoked EPSCs are shown. Traces in black are averaged from baseline recordings and in green after high-frequency stimulation (HFS) of the transcallosal projections. Long-term potentiation in layer V neurons after HFS of the transcallosal projections were decreased in TBI (red circles), compared to control (blue circles) rats. TBI, traumatic brain injury. Color image is available online at www.liebertpub.com/neu