Drug Repurposing in Neurological Disorders: Implications for Neurotherapy in Traumatic Brain Injury

2020 ◽  
pp. 107385842096107
Author(s):  
Zaynab Shakkour ◽  
Karl John Habashy ◽  
Moussa Berro ◽  
Samira Takkoush ◽  
Samar Abdelhady ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Drug Administration ◽  
Neurological Disorders ◽  
De Novo ◽  
Food And Drug Administration ◽  
Drug Repurposing ◽  
Adverse Outcomes ◽  
Minimal Risk ◽  
Wide Range

Traumatic brain injury (TBI) remains a significant leading cause of death and disability among adults and children globally. To date, there are no Food and Drug Administration–approved drugs that can substantially attenuate the sequelae of TBI. The innumerable challenges faced by the conventional de novo discovery of new pharmacological agents led to the emergence of alternative paradigm, which is drug repurposing. Repurposing of existing drugs with well-characterized mechanisms of action and human safety profiles is believed to be a promising strategy for novel drug use. Compared to the conventional discovery pathways, drug repurposing is less costly, relatively rapid, and poses minimal risk of the adverse outcomes to study on participants. In recent years, drug repurposing has covered a wide range of neurodegenerative diseases and neurological disorders including brain injury. This review highlights the advances in drug repurposing and presents some of the promising candidate drugs for potential TBI treatment along with their possible mechanisms of neuroprotection. Edaravone, glyburide, ceftriaxone, levetiracetam, and progesterone have been selected due to their potential role as putative TBI neurotherapeutic agents. These drugs are Food and Drug Administration–approved for purposes other than brain injuries; however, preclinical and clinical studies have shown their efficacy in ameliorating the various detrimental outcomes of TBI.

scholarly journals Galvos smegenų traumos žymenys. Literatūros apžvalga Biomarkers of traumatic brain injury. Literature review

2019 ◽  
Vol 23 (79) ◽  
pp. 5-12
Author(s):  
Šmigelskytė A. ◽  
Remenčiūtė M. ◽  
Ragaišis V.
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Literature Review ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
S 100

Galvos smegenų trauma (GST) – tai struktūriniai pažeidimai ir (ar) smegenų funkcionavimo sutrikdymai dėl išorinės jėgos poveikio, kuri sukelia bent vieną ūminį simptomą arba kliniškai reikšmingą šio (-ių) simptomo (-ų) pablogėjimą iš karto po įvykio: sąmonės praradimą, atminties sutrikimą apie iš karto po traumos ar prieš buvusius įvykius, psichinės būklės pokyčius traumos metu ir tam tikrus neurologinius požymius. Galvos kompiuterinė tomografija (KT) yra greitai atliekamas tyrimas, galintis nustatyti daugumą gyvybei pavojingų ir chirurginiu būdu gydomų būklių. Nors yra sudarytos galvos KT atlikimo dėl GST gairės, tačiau šio tyrimo taikymas skubios pagalbos skyriuose vis dar išlieka per dažnas dėl įtariamų lengvų GST. Norint išvengti nereikalingų KT, greitai ir efektyviai diagnozuoti GST, nustatyti jos sunkumą ir prognozuoti tolimesnę eigą, vis daugiau nagrinėjami trauminio smegenų pažeidimo žymenys. 2013 m. Skandinavijos neurotraumos komitetas (angl. Scandinavian Neurotrauma Committee) į lengvos GST diagnostikos gaires įtraukė žymens S-100 kalcio jonus surišančio baltymo β tyrimą kraujyje. 2018 m. vasario mėnesį JAV Maisto ir vaistų administracija (angl. Food and Drug Administration) patvirtino glijos skaidulinio rūgštinio baltymo ir ubikvitino C-galo hidrolazės L1 derinio naudojimą lengvos GST atveju. Tyrinėjami ir įvairūs kiti trauminio smegenų pažeidimo žymenys, tačiau jie kol kas nėra taikomi medicininėje praktikoje.

Drug Repurposing: Promises of Edaravone Target Drug in Traumatic Brain Injury

2020 ◽  
Vol 27 ◽  
Author(s):  
Zaynab Shakkour ◽  
Hawraa Issa ◽  
Helene Ismail ◽  
Ohanes Ashekyan ◽  
Karl John Habashy ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurological Disorders ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Drug Repurposing ◽  
Biochemical Properties ◽  
Phase Iii ◽  
Radical Scavenger ◽  
Neuroprotective Effects

: Edaravone is a potent free-radical scavenger that has been in the market for more than 30 years. It was originally developed in Japan to treat strokes and has been used there since 2001. Aside from its anti-oxidative effects, edaravone demonstrated beneficial effects on pro-inflammatory responses, nitric oxide production, and apoptotic cell death. Interestingly, edaravone has shown neuroprotective effects in several animal models of diseases other than stroke. In particular, edaravone administration was found to be effective in halting amyotrophic lateral sclerosis (ALS) progression during the early stages. Accordingly, after its success in Phase III clinical studies, edaravone has been approved by the FDA as a treatment for ALS patients. Considering its promises in neurological disorders and its safety in patients, edaravone is a drug of interest that can be repurposed for traumatic brain injury (TBI) treatment. Drug repurposing is a novel approach in drug development that identifies drugs for purposes other than their original indication. This review presents the biochemical properties of edaravone along with its effects on several neurological disorders in the hope that it can be adopted for treating TBI patients.

scholarly journals Traumatic Brain Injury: Effect of Litigation Status on Executive Functioning—A Pilot Study

2020 ◽  
Author(s):  
Simi Prakash K. ◽  
Rajakumari P. Reddy ◽  
Anna R. Mathulla ◽  
Jamuna Rajeswaran ◽  
Dhaval P. Shukla
Keyword(s):  
Traumatic Brain Injury ◽  
Working Memory ◽  
Depressive Symptoms ◽  
Brain Injury ◽  
Concept Formation ◽  
Verbal Working Memory ◽  
Self Report ◽  
Semantic Fluency ◽  
Set Shifting ◽  
Wide Range

AbstractTraumatic brain injury (TBI) is associated with a wide range of physiological, behavioral, emotional, and cognitive sequelae. Litigation status is one of the many factors that has an impact on recovery. The aim of this study was to compare executive functions, postconcussion, and depressive symptoms in TBI patients with and without litigation. A sample of 30 patients with TBI, 15 patients with litigation (medicolegal case [MLC]), and 15 without litigation (non-MLC) was assessed. The tools used were sociodemographic and clinical proforma, executive function tests, Rivermead Post-Concussion Symptom Questionnaire, and Beck Depression Inventory. Assessment revealed that more than 50% of patients showed deficits in category fluency, set shifting, and concept formation. The MLC group showed significant impairment on verbal working memory in comparison to the non-MLC group. The performance of both groups was comparable on tests of semantic fluency, visuospatial working memory, concept formation, set shifting, planning, and response inhibition. The MLC group showed more verbal working memory deficits in the absence of significant postconcussion and depressive symptoms on self-report measures.

scholarly journals Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

2010 ◽  
Vol 31 (1) ◽  
pp. 17-35 ◽  
Author(s):  
Martin Lauritzen ◽  
Jens Peter Dreier ◽  
Martin Fabricius ◽  
Jed A Hartings ◽  
Rudolf Graf ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurological Disorders ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Neuronal Damage ◽  
Ion Homeostasis ◽  
Large Body ◽  
Treatment Strategies ◽  
Pathophysiological Mechanism

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

Prognostic Factors for Persistent Symptoms in Adults With Mild Traumatic Brain Injury: an Overview of Systematic Reviews

2021 ◽  
Author(s):  
Julien Déry ◽  
Béatrice Ouellet ◽  
Élaine de Guise ◽  
Ève-Line Bussières ◽  
Marie-Eve Lamontagne
Keyword(s):  
Traumatic Brain Injury ◽  
Prognostic Factors ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Systematic Reviews ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Persistent Symptoms ◽  
Wide Range ◽  
Overview Of Systematic Reviews

Abstract Background: Mild traumatic brain injury (mTBI) is an increasing public health problem, because of its persistent symptoms and several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help to guide prevention of persistent symptoms following mTBI. Prognosis of mTBI has stimulated several empirical primary research papers and many systematic reviews leading to the identification of a wide range of factors. We aim to synthesize these factors to get a better understanding of their breadth and scope.Methods: We conducted an overview of systematic reviews. We searched in databases systematic reviews synthesizing evidence about prognosis of persistent symptoms after mTBI in the adult population. Two reviewers independently screened all references and selected eligible reviews based on eligibility criteria. They extracted relevant information using an extraction grid. They also rated independently the risk of bias using the ROBIS tool. We synthesized evidence into a comprehensive conceptual map to facilitate the understanding of prognostic factors that have an impact on persistent post-concussion symptoms.Results: From the 3857 references retrieved in database search, we included 25 systematic reviews integrating the results of 312 primary articles published between 1957 and 2019. We examined 35 prognostic factors from the systematics reviews. No single prognostic factor demonstrated convincing and conclusive results. However, age, sex and multiple concussions showed an affirmatory association with persistent post-concussion outcomes in systematic reviews.Conclusion: We highlighted the need of a comprehensive picture of prognostic factors related to persistent post-concussion symptoms. We believe that these prognostic factors would guide clinical decision and research related to prevention and intervention regarding persistent post-concussion symptoms.Systematic review registration: PROSPERO CRD42020176676

Development of a de novo arteriovenous malformation after severe traumatic brain injury

2014 ◽  
Vol 14 (4) ◽  
pp. 418-420 ◽  
Author(s):  
Brandon A. Miller ◽  
David I. Bass ◽  
Joshua J. Chern
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebral Cortex ◽  
Brain Injury ◽  
Arteriovenous Malformation ◽  
Severe Traumatic Brain Injury ◽  
Arteriovenous Malformations ◽  
De Novo ◽  
First Report ◽  
Congenital Lesions

Arteriovenous malformations (AVMs) are typically considered congenital lesions, although there is growing evidence for de novo formation of these lesions as well. The authors present the case of an AVM in the same cerebral cortex that had been affected by a severe traumatic brain injury (TBI) more than 6 years earlier. To the best of the authors' knowledge, this is the first report attributing the formation of an AVM directly to TBI.

scholarly journals Automated pupillometry to detect command following in neurological patients: a proof-of-concept study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6929 ◽  
Author(s):  
Alexandra Vassilieva ◽  
Markus Harboe Olsen ◽  
Costanza Peinkhofer ◽  
Gitte Moos Knudsen ◽  
Daniel Kondziella
Keyword(s):  
Brain Injury ◽  
Healthy Volunteers ◽  
Neurological Disorders ◽  
Mental Arithmetic ◽  
Proof Of Concept ◽  
Icu Patients ◽  
Wide Range ◽  
Level Of Consciousness ◽  
Neurological Patients ◽  
Command Following

Background Levels of consciousness in patients with acute and chronic brain injury are notoriously underestimated. Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in clinically unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis. Methods To assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including seven patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic. Results Fourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%) neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥4 of five arithmetic tasks. None of the five sedated and unconscious ICU patients passed this threshold. Conclusions Automated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury. We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown. If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal covert consciousness in unresponsive patients in whom standard investigations have failed to detect signs of consciousness.

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