Neurogenesis After Traumatic Brain Injury

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Neuronal loss in traumatic brain injury

Neuronal loss after TBI is focal and diffuse. Focal damage typically involves hemorrhagic lesions within the gray matter or at gray-white junctions. These contusions are typically observed at the frontal poles, orbital frontal lobes, temporal poles, and cortex above the Sylvian fissure [8]. Within contusions and adjacent neocortex of TBI patients, focal neuronal death occurs by necrotic and apoptotic mechanisms [9], [10]. Among diffuse injury sites, the hippocampus is known to be damaged

Posttraumatic hippocampal neurogenesis

In human beings, constitutive endogenous neurogenesis was demonstrated in the hippocampus after examination of postmortem tissue obtained from cancer patients who had received an intravenous infusion of bromodeoxyuridine (BrdU) for diagnostic purposes [5]. Studies from rodents demonstrate that astrocytic cells residing in the adult subgranular zone (SGZ) of the dentate gyrus continually generate neurons that migrate a short distance into the granule cell layer [16]. These new neurons

Posttraumatic subventricular zone neurogenesis

The SVZ is the largest germinal region of the adult mammalian brain, although in comparison to other species, relatively little is known regarding the contribution of human SVZ progenitor cells to adult neurogenesis. Sanai and colleagues [7] recently described a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. These investigators subsequently undertook a more detailed analysis of the

Posttraumatic cortical neurogenesis

Although the hippocampus is selectively damaged in TBI, a great deal of neuronal loss obviously occurs in focal parenchymal contusions arising in locations that vary with the specific primary or secondary injury. As discussed previously, injury signals may induce migration of neuroblasts from the SVZ, but there is also evidence for the activation of latent NPCs at sites of cortical injury in the mammalian brain. The studies of Macklis and his colleagues (eg, Magavi and coworkers [59]) in adult

Potential for therapeutic intervention

Assuming that the adult human brain is capable of generating new neurons in response to injury, as has been observed in rodents, there are still significant blockades to actual functional neuronal regeneration, with two of the foremost being glial scar formation and inflammation. To overcome the inhibitory environment of the glial scar, combinatorial treatments to provide a growth-related pathway across lesion cavities while enhancing the ability of neurons to elongate by manipulating growth

Summary

The relatively preliminary studies described here have begun to delineate aspects of the neurogenic response to TBI that should determine whether this phenomenon can be manipulated for therapeutic purposes. Clarifying the time course over which NPC proliferation, migration, differentiation, and integration occur after injury is necessary for defining therapeutic windows in which to attempt to augment these processes. From studies thus far, it is known that there are an increased number of

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  • Cited by (147)

    • Traumatic brain injury modifies synaptic plasticity in newly-generated granule cells of the adult hippocampus

      2021, Experimental Neurology
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      While research into effective neuroprotective strategies is essential, there is growing interest in cell-based and pharmacological therapies that enhance endogenous neurorestorative processes by facilitating neurogenesis, synaptogenesis, angiogenesis, and axonal remodeling (e.g., review by Xiong et al., 2015). Work in our laboratory, and others, has demonstrated hippocampal neurogenesis to be an endogenous process which may be enhanced to benefit innate restorative processes after TBI (Dash et al., 2001; Richardson et al., 2007; Sun et al., 2007, 2009, 2015; Weston and Sun, 2018). The dentate gyrus (DG) of the hippocampus is known to serve an essential role in learning and memory, while being extremely vulnerable to TBI.

    • Photobiomodulation for traumatic brain injury in mouse models

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    This work was supported by Commonwealth of Virginia Neurotrauma Initiative grant 02-319 (MRB).

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