Neurostimulation for Traumatic Brain Injury: Emerging Innovation (original) (raw)
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Brain Sciences
Neurostimulation carries high therapeutic potential, accompanied by an excellent safety profile. In this review, we argue that an arena in which these tools could provide breakthrough benefits is traumatic brain injury (TBI). TBI is a major health problem worldwide, with the majority of cases identified as mild TBI (mTBI). MTBI is of concern because it is a modifiable risk factor for dementia. A major challenge in studying mTBI is its inherent heterogeneity across a large feature space (e.g., etiology, age of injury, sex, treatment, initial health status, etc.). Parallel lines of research in human and rodent mTBI can be collated to take advantage of the full suite of neuroscience tools, from neuroimaging (electroencephalography: EEG; functional magnetic resonance imaging: fMRI; diffusion tensor imaging: DTI) to biochemical assays. Despite these attractive components and the need for effective treatments, there are at least two major challenges to implementation. First, there is insu...
Traumatic brain injury (TBI) is one of the growing public health problems and a leading cause of disabilities and mortality worldwide. After the mechanical impact to the head, patients of all ages suffer from cognitive and neurological deficits, as well as psychological disorders to different extents. In the last years, the use of electrical impulses and magnetic currents to achieve therapeutic effects have shown promising results and became potential treatments for TBI. Potential mechanisms of action described so far include long term potentiation and depression of neuronal synapses, stimulation of neurotransmitters and growth factors release, and reduction of neuroinflammation, apoptosis and excitotoxicity, among others. Although promising results have been obtained in pre clinical experiments and limited clinical studies, the high rate of variability in technical parameters and the limited number of patients enrolled have made difficult to clearly define the optimal conditions to obtain reliable therapeutic effects with these stimulation techniques in TBI patients. The present review aims to describe the molecular processes taking place in the brain after the injury, as well as to describe some of the neurostimulation treatments currently under development for TBI management.
Operation Brain Trauma Therapy: 2016 Update
Operation brain trauma therapy (OBTT) is a multi-center, pre-clinical drug and biomarker screening consortium for traumatic brain injury (TBI). Therapies are screened across three rat models (parasagittal fluid percussion injury, controlled cortical impact [CCI], and penetrating ballistic-like brain injury). Operation brain trauma therapy seeks to define therapies that show efficacy across models that should have the best chance in randomized clinical trials (RCTs) and/or to define model-dependent therapeutic effects, including TBI protein biomarker responses, to guide precision medicine-based clinical trials in targeted pathologies. The results of the first five therapies tested by OBTT (nicotinamide, erythropoietin, cyclosporine [CsA], simvastatin, and levetiracetam) were published in the Journal of Neurotrauma. Operation brain trauma therapy now describes preliminary results on four additional therapies (glibenclamide, kollidon-VA64, AER-271, and amantadine). To date, levetiracetam was beneficial on cognitive outcome, histology, and/or biomarkers in two models. The second most successful drug, glibenclamide, improved motor function and histology in CCI. Other therapies showed model-dependent effects (amantadine and CsA). Critically, glial fibrillary acidic protein levels predicted treatment effects. Operation brain trauma therapy suggests that levetiracetam merits additional pre-clinical and clinical evaluation and that glibenclamide and amantadine merit testing in specific TBI phenotypes. Operation brain trauma therapy has established that rigorous, multi-center consortia could revolutionize TBI therapy and biomarker development.
Recent Advances and Future Trends in Traumatic Brain Injury
Traumatic brain injury (TBI) has been called a silent epidemic and is a major health and socioeconomic problem. TBI is the leading cause of morbidity and mortality among young adults in developed economies and the incidence in the elderly population is increasing. In developing countries the incidence of TBI is high and rapidly increasing. The World Health Organization predicts that TBI and road traffic accidents will be the third greatest cause of disease and injury worldwide by 2020. TBI is a heterogeneous condition in terms of etiology, severity, and outcome. Currently, no effective TBI therapy exists, with patients treated through a combination of surgery, rehabilitation and pharmacological agents managing post-trauma conditions such as depression. Evidence-based guidelines and management protocols help to guide target-driven care and are associated with better outcome. Continuous attempts have been made worldwide to discover the best possible treatment, but an effective treatment method is not yet available. Evidence-based intensive care management strategies improves outcome. The most definite benefits in terms of survival after TBI come from admission to a specialist neurosurgical centre, with goal-targeted therapy and intensive care services. Early detection and objective characterization of abnormalities in TBI are important objectives of modern neuroimaging. Improved treatment will come through understanding the physical changes in the brain that occur at the microscopic and molecular levels when the brain is subject to trauma. Novel achievements in neuroprotection are now expected from developing antiapoptotic agents, from more potent antioxidants, cholinergic agents, alpha blockers, from researching various physiological substances, advances in molecular medicine including stem cell and gene therapy. A more analytical approach to understanding the complex array of factors that influence the incidence, severity, and outcome of TBI is essential. Future therapies that are currently under investigation hold promise. Unless systematic efforts are made towards prevention, management and rehabilitation, many more individuals, children and middle-aged adults will continue to die. There is a strong need to enhance TBI prevention and to improve treatment. Appropriate targeting of prevention and improving outcome requires a detailed understanding of incidence, causes of injury, treatment approaches and outcome results. Specific topics addressed in this paper include scientific understanding of the problem in its various dimensions, complexities and controversies regarding diagnostic and therapeutic modalities, outcome and impact of TBIs on rapidly transforming societies, challenges and opportunities in research and linking research to practice. Improved patient outcomes will depend on organised trauma response systems, particularly to prevent the potentially reversible effects of secondary brain injury strategies.
International journal of molecular sciences, 2014
Traumatic Brain Injury (TBI) affects a large proportion and extensive array of individuals in the population. While precise pathological mechanisms are lacking, the growing base of knowledge concerning TBI has put increased emphasis on its understanding and treatment. Most treatments of TBI are aimed at ameliorating secondary insults arising from the injury; these insults can be characterized with respect to time post-injury, including early, intermediate, and late pathological changes. Early pathological responses are due to energy depletion and cell death secondary to excitotoxicity, the intermediate phase is characterized by neuroinflammation and the late stage by increased susceptibility to seizures and epilepsy. Current treatments of TBI have been tailored to these distinct pathological stages with some overlap. Many prophylactic, pharmacologic, and surgical treatments are used post-TBI to halt the progression of these pathologic reactions. In the present review, we discuss the...
Initial neurocritical care of severe traumatic brain injury: New paradigms and old challenges
Surgical Neurology International
Background: Early neurocritical care aims to ameliorate secondary traumatic brain injury (TBI) and improve neural salvage. Increased engagement of neurosurgeons in neurocritical care is warranted as daily briefings between the intensivist and the neurosurgeon are considered a quality indicator for TBI care. Hence, neurosurgeons should be aware of the latest evidence in the neurocritical care of severe TBI (sTBI). Methods: We conducted a narrative literature review of bibliographic databases (PubMed and Scopus) to examine recent research of sTBI. Results: This review has several take-away messages. The concept of critical neuroworsening and its possible causes is discussed. Static thresholds of intracranial pressure (ICP) and cerebral perfusion pressure may not be optimal for all patients. The use of dynamic cerebrovascular reactivity indices such as the pressure reactivity index can facilitate individualized treatment decisions. The use of ICP monitoring to tailor treatment of intra...
Neuromodulation : journal of the International Neuromodulation Society, 2017
Neurostimulation involves the implantation of devices to stimulate the brain, spinal cord, or peripheral or cranial nerves for the purpose of modulating the neural activity of the targeted structures to achieve specific therapeutic effects. Surgical placement of neurostimulation devices is associated with risks of neurologic injury, as well as possible sequelae from the local or systemic effects of the intervention. The goal of the Neurostimulation Appropriateness Consensus Committee (NACC) is to improve the safety of neurostimulation. The International Neuromodulation Society (INS) is dedicated to improving neurostimulation efficacy and patient safety. Over the past two decades the INS has established a process to use best evidence to improve care. This article updates work published by the NACC in 2014. NACC authors were chosen based on nomination to the INS executive board and were selected based on publications, academic acumen, international impact, and diversity. In areas in w...
Synthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy
Journal of neurotrauma, 2015
Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous, and productive multi-center, pre-clinical drug and circulating biomarker screening consortium for the field of traumatic brain injury (TBI). In this manuscript, we synthesize the findings from the first five therapies tested by OBTT, and discuss both the current work that is ongoing and potential future directions. Based on the results generated from the first five therapies tested within the exacting approach used by OBTT, four (nicotinamide, erythropoietin, cyclosporine A, and simvastatin) performed below or well below what was expected based on the published literature. However, OBTT has identified the early post-TBI administration of levetiracetam as a promising agent and has advanced it to a gyrencephalic large animal model-- fluid percussion injury in micropigs. The 6th and 7th therapies have just completed testing (glibenclamide and Kollidon VA 64) and an 8th drug (AER 271) is in testing. Incorporation of...