Neuromodulation Therapies in Pre-Clinical Models of Traumatic Brain Injury: Systematic Review and Translational Applications

Surendrakumar, Shanan; Rabelo, Thallita Kelly; Campos, Ana Carolina Pinheiro; Mollica, Adriano; Abrahão, Agessandro; Lipsman, Nir; Burke, Matthew J.; Hamani, Clement

doi:10.1089/neu.2022.0286

Cited by 12 publications

(14 citation statements)

References 76 publications

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“…While the majority of the clinical and preclinical literature has examined pharmacologic interventions for TBI, nonpharmacologic interventions, including neuromodulation, lifestyle modification, physical exercise, and nutraceuticals, have been trialed in clinical and preclinical studies of TBI [ 81 , 82 , 83 ]. A treatment approach using combined nonpharmacologic interventions has a similar potential as pharmacologic interventions to address the evolving pathophysiology of TBI-induced secondary injury, modulating different molecular targets at different time points.…”

Section: Resultsmentioning

confidence: 99%

“…Non-pharmacologic interventions offer some promise in the multimodal treatment of secondary injury after TBI, for several reasons. Many non-pharmacologic interventions, such as neuromodulation and nutraceuticals, can be initiated without disrupting ongoing treatment and have a favorable risk/benefit profile [ 81 , 82 ], which makes it easier to apply them alongside other therapies to address TBI as it evolves. However, much like for pharmacologic interventions, the blind application of non-pharmacologic treatment techniques without a detailed understanding of the patient’s physiologic state at the time of application, as well as knowledge of the molecular targets of the intervention, is likely to fail.…”

Section: Discussionmentioning

confidence: 99%

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Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch

Narayan

2023

JCM

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch

Narayan

2023

JCM

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“…The most prevalent electrical stimulation methods used in post-TBI treatment studies, which are in the focus of this review, are transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS) and vagus nerve stimulation (VNS) [ 25 , 79 ]. TMS and tDCS are amongst the most commonly used non-invasive brain stimulation techniques [ 80 , 81 ].…”

Section: State-of-the-artmentioning

confidence: 99%

“…Another important part of the stimulation protocol is the timing of the treatment application after injury, which depends on the selected treatment modality, the severity of the trauma and the goal of the treatment [ 135 ]. The onset of stimulation in preclinical studies varies from immediately to several weeks after trauma [ 25 ]. In clinical settings, these techniques are usually applied at later stages as a support to traditional rehabilitation methods for treating disabilities that persist after TBI [ 114 , 136 ].…”

Section: State-of-the-artmentioning

confidence: 99%

“…Although the limited capabilities of nervous tissue to self-repair hinders complete regeneration of damaged brain tissue, processes involved in neuroplasticity can at least partially restore neuronal connectivity. Promising results observed in preclinical and clinical studies with electrical stimulation provide a good basis for the exploitation of neuroplasticity for functional restoration to alleviate trauma-induced disabilities [ 24 , 25 ]. Hypo- or hyper-excitability, for instance, provide suitable targets for neuromodulatory interventions such as transcranial magnetic stimulation and deep brain stimulation [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research

Ziesel

Nowakowska

Scheruebel

et al. 2023

J NeuroEngineering Rehabil

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Background Traumatic brain injury (TBI) is a leading cause of disabilities resulting from cognitive and neurological deficits, as well as psychological disorders. Only recently, preclinical research on electrical stimulation methods as a potential treatment of TBI sequelae has gained more traction. However, the underlying mechanisms of the anticipated improvements induced by these methods are still not fully understood. It remains unclear in which stage after TBI they are best applied to optimize the therapeutic outcome, preferably with persisting effects. Studies with animal models address these questions and investigate beneficial long- and short-term changes mediated by these novel modalities. Methods In this review, we present the state-of-the-art in preclinical research on electrical stimulation methods used to treat TBI sequelae. We analyze publications on the most commonly used electrical stimulation methods, namely transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS) and vagus nerve stimulation (VNS), that aim to treat disabilities caused by TBI. We discuss applied stimulation parameters, such as the amplitude, frequency, and length of stimulation, as well as stimulation time frames, specifically the onset of stimulation, how often stimulation sessions were repeated and the total length of the treatment. These parameters are then analyzed in the context of injury severity, the disability under investigation and the stimulated location, and the resulting therapeutic effects are compared. We provide a comprehensive and critical review and discuss directions for future research. Results and conclusion We find that the parameters used in studies on each of these stimulation methods vary widely, making it difficult to draw direct comparisons between stimulation protocols and therapeutic outcome. Persisting beneficial effects and adverse consequences of electrical simulation are rarely investigated, leaving many questions about their suitability for clinical applications. Nevertheless, we conclude that the stimulation methods discussed here show promising results that could be further supported by additional research in this field.

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Bibliometric and visual analysis of severe trauma literature in the past 20 years

Chang,

Li,

Wang

et al. 2024

MedComm – Future Medicine

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Severe trauma is a critical aspect of medical practice, profoundly impacting patient care and outcomes. Over the past 20 years, advancements in trauma care concepts and the utilization of advanced technologies have led to substantial growth in severe trauma research, evidenced by a notable increase in research activity and subsequent publications. To understand the publication landscape in severe trauma, identify prevailing research trends, and highlight areas requiring further development for future insights, we conducted a bibliometric analysis. Our analysis indicates that there are 16,939 severe trauma‐related publications from the past 20 years, with a continuous increase in publication volume, particularly showing a rapid growth trend from 2018 to 2021. The United States leads in both volume and citation frequency. Moreover, we synthesized data on productive countries/regions and research institutions, showcasing extensive collaboration across diverse geographic locations and institutional affiliations. Substantial progress has been achieved in severe trauma research, particularly in clinical diagnosis, treatment, epidemiology, prevention, and pathogenesis. However, there is still a gap in adopting cutting‐edge interdisciplinary methodologies. This study provides a comprehensive overview of the current state of severe trauma research and suggests pathways for future advancement.

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Neuromodulation Therapies in Pre-Clinical Models of Traumatic Brain Injury: Systematic Review and Translational Applications

Cited by 12 publications

References 76 publications

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research

Bibliometric and visual analysis of severe trauma literature in the past 20 years

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