Abstract
Hippocampal injury-associated learning and memory deficits are frequent hallmarks of brain trauma and are the most enduring and devastating consequences following traumatic brain injury (TBI). Several reports, including our recent paper, showed that TBI brought on by a moderate level of controlled cortical impact (CCI) induces immature newborn neuron death in the hippocampal dentate gyrus. In contrast, the majority of mature neurons are spared. Less research has been focused on these spared neurons, which may also be injured or compromised by TBI. Here we examined the dendrite morphologies, dendritic spines, and synaptic structures using a genetic approach in combination with immunohistochemistry and Golgi staining. We found that although most of the mature granular neurons were spared following TBI at a moderate level of impact, they exhibited dramatic dendritic beading and fragmentation, decreased number of dendritic branches, and a lower density of dendritic spines, particularly the mushroom-shaped mature spines. Further studies showed that the density of synapses in the molecular layer of the hippocampal dentate gyrus was significantly reduced. The electrophysiological activity of neurons was impaired as well. These results indicate that TBI not only induces cell death in immature granular neurons, it also causes significant dendritic and synaptic degeneration in pathohistology. TBI also impairs the function of the spared mature granular neurons in the hippocampal dentate gyrus. These observations point to a potential anatomic substrate to explain, in part, the development of posttraumatic memory deficits. They also indicate that dendritic damage in the hippocampal dentate gyrus may serve as a therapeutic target following TBI.
Highlights
Traumatic brain injury (TBI) results in immediate CNS tissue disruption, and causes secondary damage among the surviving cells via complex mechanisms triggered by the primary event [1,2]
Decreased Nissl staining of spared neurons may be a reflection of cell stress. These results indicate that TBI caused by a moderate level of impact may lead to cell stress but does not obviously change the architecture of the hippocampus, and the majority of the mature granular neurons in the hippocampal dentate gyrus (HDG) survived but stressed at this level of cortical impact (CCI)-injury
In order to further assess the subtle degeneration of those spared mature granular neurons in the HDG following TBI, we evaluated their dendrites, dendritic spines, and synapses following moderate cortical controlled impact (CCI) injury
Summary
Traumatic brain injury (TBI) results in immediate CNS tissue disruption (primary injury), and causes secondary damage among the surviving cells via complex mechanisms triggered by the primary event [1,2]. This secondary injury initiated by the primary impact leads to persistent cognitive, sensory, and motor dysfunction [3]. The hippocampus undergoes similar neuropathological changes after both human closed-head injury and experimental injury models of TBI, including controlled cortical impact (CCI) injury [2,4], fluid percussion [5], and stretch injury [6]. It is critically important to understand the molecular and cellular mechanisms behind learning and memory impairment following TBI in hopes of finding a way to prevent the progression of damage or encourage the recovery of learning and memory
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