Is being plastic fantastic? Mechanisms of altered plasticity after developmental traumatic brain injury

Abstract

Traumatic brain injury (TBI) is predominantly a clinical problem of young persons, resulting in chronic cognitive and behavioral deficits. Specifically, the physiological response to a diffuse biomechanical injury in a maturing brain can clearly alter normal neuroplasticity. To properly evaluate and investigate developmental TBI requires an understanding of normal principles of cerebral maturation, as well as a consideration of experience-dependent changes. Changes in neuroplasticity may occur through many age-specific processes, and our understanding of these responses at a basic neuroscience level is only beginning. In this article, we will particularly discuss mechanisms of TBI-induced altered developmental plasticity such as altered neurotransmission, distinct molecular responses, cell death, perturbations in neuronal connectivity, experience-dependent 'good plasticity' enhancements and chronic 'bad plasticity' sequelae. From this summary, we can conclude that 'young is not always better' and that the developing brain manifests several crucial vulnerabilities to TBI.

Fig. 1

Recovery of function after injury in different theoretical models. a Static (mature) model: baseline function does not change with time (solid line). Injury with no recovery shows downward step in function (dotted line). Injury with gradual return to premorbid baseline results in complete recovery (dashed line). b Dynamic (developmental) model: baseline function improves with time (solid line). Injury with gradual return to premorbid baseline results in incomplete recovery (dashed line). c Dynamic (interventional) model: baseline function shows no change with time (thin solid line), but following intervention, baseline function improves with time (thick solid line). Injury (followed by intervention) with return to premorbid baseline represents incomplete recovery (dashed line).

Fig. 2

Gene expression changes by functional category after mild and severe developmental brain injury. a Proportion of gene changes ascribed to specific functional categories following mild injury. The greatest proportion of downregulated genes can be classified as genes related to neurotransmission/plasticity or growth factors/hormones. b Proportion of gene changes ascribed to specific functional categories following severe injury. Again, genes associated with neurotransmission/plasticity and growth factors/hormones represent a much larger percentage of downregulated than upregulated genes. ROS = Reactive oxygen species.