Synaptogenesis in the Hippocampal CA1 Field following Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) results in both acute and chronic disruption of cognitive ability that may be mediated through a disruption of hippocampal circuitry. Experimental models of TBI have demonstrated that cortical contusion injuries can result in the loss of specific neurons in the CA3 subfield of the ipsilateral hippocampus, resulting in partial loss of afferents to the CA1 subfield. Numerous studies have documented the ability of the central nervous system to compensate for deafferentation by initiating a plasticity response capable of restoring lost synaptic contacts. The present study was designed to examine the time course of loss and replacement of synaptic contacts in stratum radiatum dendritic field of CA1. Young adult rats were subjected to a lateral cortical contusion injury and assayed for total synaptic numbers using unbiased stereology coupled with transmission electron microscopy. Injured animals demonstrated a 60% loss of synapses in CA1 at 2 days post-injury, followed by a reinnervation process that was apparent as early as 10 days post-injury. By 60 days post-injury, total synaptic numbers had approached pre-injury levels but were still significantly lower. Some animals were behaviorally tested for spatial memory in a Morris Water Maze at 15 and 30 days post-injury. While there was some improvement in spatial memory, injured animals continued to demonstrate a significant deficit in acquisition. These results show that the hippocampus ipsilateral to the cortical contusion is capable of a significant plasticity response but that synapse replacement in this area does not necessarily result in significant improvement in spatial learning.

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

“…Altered energy metabolism and oxidative stress negatively affects synaptic plasticity and cognitive function though oxidation of synaptic proteins [18,20]. Oxidative stress contributes to synaptic dysfunction and disconnection, with impaired mitochondrial transport to the synapses contributing to both neuronal death and neuritic degenerative cascades [15,16].…”

“…As a consequence of oxidative stress both the function and transport of mitochondrial to synaptic regions is impaired, decrease synaptic function [15,16], which results in neurodegeneration after brain injury [17,18]. A recent study reported that oxidative stress alters the function of PSD-95 by decreasing a voltage-gated potassium channel that is closely linked to the PSD [19], suggesting that synapse loss and replacement, known to occur following TBI [20], could be modulated by the levels of oxidative stress.…”

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

“…Acute perturbations of glial function and ionic fluxes highlight the transient nature of injury-induced alterations that can alter excitability [21,45]. Lastly, disruption of synapse function or number [77,80], without neuronal loss, could contribute to the acute injury-induced deficits in conditioned fear, prompting future studies at the ultrastructural level. It follows, therefore, that the natural course of functional recovery in experimental and clinical TBI may be amenable to therapeutic intervention to overcome the transient lesion.…”

Dose- and Time-Dependent Neuroprotective Effects of Pycnogenol® following Traumatic Brain Injury

“…1 Multiple primary and secondary injury cascades are involved in TBI, which result in delayed neuronal dysfunction, synapse loss, and cell death. [2][3][4][5][6][7][8][9] These secondary injury cascades can occur very rapidly, within minutes or hours after the trauma and last for days or weeks. Although there are many different factors, most researchers believe that pharmacologic intervention following trauma can disrupt these cascades and result in a more positive outcome.…”