Neurogenesis After Traumatic Brain Injury
Section snippets
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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2021, Experimental NeurologyCitation Excerpt :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.
Protein biomarkers of epileptogenicity after traumatic brain injury
2019, Neurobiology of DiseasePhotobiomodulation for traumatic brain injury in mouse models
2019, Photobiomodulation in the Brain: Low-Level Laser (Light) Therapy in Neurology and Neuroscience
This work was supported by Commonwealth of Virginia Neurotrauma Initiative grant 02-319 (MRB).