There currently exist limited treatment options leading to significant structural and functional recovery following a traumatic brain injury (TBI). Researchers are currently analyzing a variety of immediate and long-term treatment options that can aid in TBI recovery. These methods include pharmacological treatments, transcranial magnetic stimulation (TMS), physical therapy, stem cell transplants, and other methods. These ongoing studies have the potential to improve patient outcomes and revolutionize the standard procedures for treating TBIs.
In the article “Neuromodulatory Interventions for Traumatic Brain Injury,” Dr. Pape and colleagues discuss the potential for TMS to serve as a noninvasive TBI treatment. They studied the impact of TMS on both abnormal and non-abnormal neural circuits, following a TBI, to encourage functional recovery and decrease TBI symptoms. TMS treatments aim to assist in patient recovery by promoting synaptic plasticity and metaplasticity through the creation and re-organization of synaptic connections. However, this treatment’s success is measured in terms of observable behavioral changes. Patients’ abilities to re-learn or restore skills impacted by their TBI are utilized to assess TMS’s efficacy. TMS treatments were not limited to a specific pathology or source of TBI.
A more invasive treatment option, explored in the article “Amelioration of Penetrating Ballistic-Like Brain Injury Induced Cognitive Deficits after Neuronal Differentiation of Transplanted Human Neural Stem Cells” (Spurlock et. al., 2017), is focused on penetrating traumatic brain injuries (PTBI) such as gunshot wound head traumas. PBTIs are often accompanied by a dramatic loss of neurons. The treatment option explored by Dr. Spurlock and colleagues involves the engraftment of human neural stem cells (hNSC) and the administration of immunosuppressants (to prevent transplant rejections). In this study, PTBIs were induced in rats and then, seven to ten days later, the rats were given hNSC grafts. Both behavior and pathology were examined at various intervals, including eight and sixteen weeks post-transplant, to assess treatment efficacy. Eight weeks after the hNSC transplant, this study assessed rats’ memory and learning capabilities with the Morris Water Maze test. It was determined that rats who received the neural stem cell transplant after PBTI learned the maze faster and experienced shorter latency than rats who did not receive a neural stem cell transplant after PBTI. Sixteen weeks after the hNSC transplant, the transplanted cells had transitioned from the original undifferentiated state into the same morphology as nearby neurons. This demonstrates that, with time, the hNSC differentiated. The brains were periodically fluorescently stained and brain imaging was used to calculate the approximate number of surviving neural stem cells. It was determined that, on average, there existed 150% of the original number of transplanted neurons following hNSC treatment. This transplant size remained consistent from week 5 post-transplant until week 16 post-transplant when the study concluded. Furthermore, at 16 weeks, there was minimal cell migration as transplanted cells stayed near the graft sites; however, fluorescently tagged transplanted cells could be seen extending along white matter tracts. Despite this neuron growth, there was a lack of markers associated with the myelination of neurons. This indicates that, despite differentiating, the engrafted cells did not become myelinated. Overall, these results indicate that the introduction of human neural stem cell grafts with immunosuppressants may be a viable treatment for traumatic brain injuries in which there is a significant loss of neurons.
While the treatment methods analyzed by Dr. Pape and Dr. Spurlock appear vastly different, they achieve a similar goal through the implementation of synaptic plasticity and neuron regeneration in a therapeutic manner. Although the noninvasive method studied by Dr. Pape has more general applications while the method studied by Dr. Spurlock is targeted towards a specific pathology of TBI, these treatments have similar clinical applications. Since TBI recovery can be simultaneously treated with more than one method, these two treatment methods could be used together. While the neural stem cell transplant treatment is utilized to replace damaged or lost neurons, the TMS method can be used to promote connectivity between new and existing neurons so that the necessary networks can form. This combination of treatments may allow patients to re-learn skills more efficiently than they would with either treatment method alone.
Overall, it is important to recognize the interaction between different clinical discoveries as these treatments do not function in an isolated vacuum. Clinicians must weigh the benefits and risks of each treatment option and consider whether it is appropriate to utilize more than one option at a time. Acknowledging their combined potential can create novel opportunities and enhance patient care. It is exciting to consider the variety of contexts in which these treatments could improve someone’s quality of life. However, in addition to considering the potential benefits of combining these treatments, and possibly other treatments, it is also necessary to consider negative interactions of combined treatments or elevated risks for side effects.
Bender Pape TL, Herrold AA, Guernon A, Aaronson A, Rosenow JM. Neuromodulatory
Interventions for Traumatic Brain Injury. J Head Trauma Rehabil. 2020 Nov-Dec;35(6):365-370. doi: 10.1097/HTR.0000000000000643. PMID: 33165150.
Spurlock MS, Ahmed AI, Rivera KN, Yokobori S, Lee SW, Sam PN, et al. Amelioration of
penetrating ballistic-like brain injury induced cognitive deficits after neuronal differentiation of transplanted human neural stem cells. J Neurotrauma. 2017;34(11):1981–95. https://doi.org/10.1089/neu.2016.4602.
Weston, N.M., Sun, D. The Potential of Stem Cells in Treatment of Traumatic Brain Injury.
Curr Neurol Neurosci Rep 18, 1 (2018). https://doi.org/10.1007/s11910-018-0812-z.
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