Focal Damage to the Adult Rat Neocortex Induces Wound Healing Accompanied by Axonal Sprouting and Dendritic Structural Plasticity

Abstract

Accumulating evidence indicates that damage to the adult mammalian brain evokes an array of adaptive cellular responses and may retain a capacity for structural plasticity. We have investigated the cellular and architectural alterations following focal experimental brain injury, as well as the specific capacity for structural remodeling of neuronal processes in a subset of cortical interneurons. Focal acute injury was induced by transient insertion of a needle into the neocortex of anesthetized adult male Hooded-Wistar rats and thy1 green fluorescent protein (GFP) mice. Immunohistochemical, electron microscopy, and bromodeoxyuridine cell proliferation studies demonstrated an active and evolving response of the brain to injury, indicating astrocytic but not neuronal proliferation. Immunolabeling for the neuron-specific markers phosphorylated neurofilaments, α-internexin and calretinin at 7 days post injury (DPI) indicated phosphorylated neurofilaments and α-internexin but not calretinin immunopositive axonal sprouts within the injury site. However, quantitative studies indicated a significant realignment of horizontally projecting dendrites of calretinin-labeled interneurons at 14 DPI. This remodeling was specific to calretinin immunopositive interneurons and did not occur in a subpopulation of pyramidal neurons expressing GFP in the injured mouse cortex. These data show that subclasses of cortical interneurons are capable of adaptive structural remodeling.

In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits

“…We hypothesized that axons that normally display a high rate of synaptic and branch remodelling, that is, from Layer (L) 6 cortical cells would more readily respond to a lesion than axons that are typically more stable, that is, thalamocortical axons (TCA) projecting to the upper layers of the cortex 8 . This intrinsically specified plasticity is reminiscent of the differences in regeneration between different axonal tracts following injury [9][10][11] .…”

Mild Traumatic Brain Injury Leads to Decreased Inhibition and a Differential Response of Calretinin Positive Interneurons in the Injured Cortex

“…50 It is well established that after a traumatic injury to the brain, neurons can respond and attempt regeneration through the spontaneous rearrangement of the affected network in the form of compensatory morphological or structural plasticity; however, the role that neuronal plasticity plays in mild forms of trauma is not clear. 20 • 51 The current study utilized two contrasting models of injury (in vivo mild diffuse injury vs. in vitro single complete neurite transection in relatively mature neurons) to investigate the response of intemeurons, focusing on calretinin+ intemeurons, to injury. Mild injuries in vivo were confirmed by the lack of clear structural damage, absence of postinjury mortality, and short time required for mice to regain their righting reflex post-TBI.…”

“…However, studies examining a discreet focal injury to the somatosensory cortex indicate that subpopulations of intemeurons, specifically the calretinin + intemeurons, have an underappreciated potential for plasticity and remodeling following trauma. 20 Calretinin+ intemeurons represent approximately 10-30% of the total intemeuron population in the cortex. 33 Even though this is a relatively small fraction of the inhibitory neurons, their unique connectivity and placement in the circuitry affords them significant control over inhibitory regulation as a whole.…”

Regulation of Basal and Injury-Induced Fate Decisions of Adult Neural Precursor Cells: Focus on SOCS2 and Related Signalling Pathways

“…A traumatic lesion to the brain cortex results in an increase in proliferation of NSCs in the SVZ, although varied locations and degrees of injury have resulted in an incongruity of results across the literature [93][94][95][96][97][98]. Nonetheless, it is generally agreed that the increase in proliferation results in an increase in neurogenesis at the SVZ [99].…”

“…Unfortunately, this does not appear to be consistent. Recent work on ischemia has demonstrated that new neurons from the SVZ are found in the cortex near the lesioned area, while injury of the somatosensory cortex showed the generation of astrocytes and microglia/macrophages without any new neurons [98,121]. Other work has found the production of astrocytes and oligodendrocytes near the injury site as a result of expression of repressors of neuronal fate [122,123].…”