Brain-derived neurotrophic factor in traumatic brain injury, post-traumatic stress disorder, and their comorbid conditions: role in pathogenesis and treatment

Abstract

As US military service members return from the wars in Iraq and Afghanistan with elevated rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), attention has been increasingly focused on TBI/PTSD comorbidity, its neurobiological mechanisms, and novel and effective treatment approaches. TBI and PTSD, and their comorbid conditions, present with a spectrum of common clinical features such as sleep disturbance, depression, anxiety, irritability, difficulty in concentrating, fatigue, suicidality, chronic pain, and alterations in arousal. These TBI and PTSD disorders are also thought to be characterized by overlapping neural mechanisms. Both conditions are associated with changes in hippocampal, prefrontal cortical, and limbic region function because of alterations in synaptogenesis, dendritic remodeling, and neurogenesis. Neural changes in TBI and PTSD result from pathophysiological disturbances in metabolic, cytotoxic, inflammatory, and apoptic processes, amongst other mechanisms. Neurotrophins have well-established actions in regulating cell growth and survival, differentiation, apoptosis, and cytoskeleton restructuring. A body of research indicates that dysregulation of neural brain-derived neurotrophic factor (BDNF) is found in conditions of TBI and PTSD. Induction of BDNF and activation of its intracellular receptors can produce neural regeneration, reconnection, and dendritic sprouting, and can improve synaptic efficacy. In this review, we consider treatment approaches that enhance BDNF-related signaling and have the potential to restore neural connectivity. Such treatment approaches could facilitate neuroplastic changes that lead to adaptive neural repair and reverse cognitive and emotional deficits in both TBI and PTSD.

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

“…A small population of BrdU1 cells remains unaccounted for by newly formed neurons and astrocytes suggesting that LM11A-31 promotes proliferation/survival of other cell populations; the delineation of these and determination of their roles in recovery will be the subject of future studies. Finally, it is of interest that BDNF, which has been implicated as a significant factor in TBI recovery [69] and may have direct [70] and indirect [71] effects on neural progenitors via TrkB-family receptors, was divergent from LM11A-31 and NGF in its effects on Figure 7. Controlled cortical impact (CCI) and LM11A-31 effects on spatial memory performance.…”

The Photobiomodulatory Therapy and ILIB in the Repair of Encephalic Cisterns and Progressive Cognitive Restoration in a Patient with Traumatic Brain Injury

“…The Low Intensity Laser (LBI/ILIB) used for global patient recovery is considered beneficial [14,15] in a variety of different modalities due to its photobiomodulatory effect, and the most important transcranial laser therapy for TBI is related to neuronal repair and neurogenesis, not only in the formation of new brain cells, but also in synaptogenesis [16], which is the formation of new connections between existing brain cells. And in this study, after the photobiomodulatory intervention, a cognitive and functional restoration took place that conditioned a scientific-literary interpretation ratifying the possible activation of brain cells by the repeated processes of neurogenesis and synaptogenesis, potentiated, in a supportive way, by the photobiomodulator protocol.…”

“…The results were measured by the Rancho los Amigos Cognitive Levels Scale [5][6][7][8][9][10][11][12][13][14][15][16][17], represented by the state of agitation or inappropriateness and functional capacity, divided into ten levels, which assign values to the different levels of brain function, according to the patient's reaction to external stimuli. In this study, the patient reached an evolution from level 1 to level 3, and reestablishment of brain cisterns (axial section) in the image examination …”

“…Secondary lesions may be due to inflammation, glutamate excitotoxicity, cell necrosis, glial proliferation, mitochondrial dysfunction, apoptosis, and oxygen free radical production and diffuse axonal injury [12][13][14][15]. These pathological alterations result in changes in synaptogenesis, dendritic remodeling and neurogenesis in the cortical and limbal regions of the hippocampus, prefrontally [16]. It is suggested that the intervention of the LIB in the muscular structures stimulated the fascias in a complementary way potentiating the drug effect and reducing the inflammatory process in the hemoventrículos, besides the systemic function ILIB to stimulate the photoenteral route in the process of apoptosis without corrupting the organ nocientemente and activation of new cellular synapses [16] in the compromised lobe.…”

Neurogenic hypothesis and psychiatric disorders

“…Chronic SSRI treatment was able to rescue the decreased neurogenesis and decrease the hyperactive behavior simultaneously. Mechanistically, the disturbance of BDNF signaling in PTSD patients suggested a possible connection between neurogenesis and PTSD condition [63]. Although the data about the relationship between PTSD and neurogenesis seem to be promising, the hypothesis needs to be further confirmed by more in-depth pre-clinical and clinical studies.…”