Abstract
Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological deficits. The delayed secondary brain injury is likely to result from multiple insults including oxidative stress, mitochondrial dysfunction, breakdown of the blood brain barrier, dysregulated release of glutamate, pro-inflammatory cytokines, and other mediators. However, therapies targeting these systems have generally met with failure in clinical trials. The purpose of this review is to summarize the models used for preclinical neurotrauma research, provide a brief overview of previous failed clinical trials in head and spinal cord injury, and finally, to review involvement of the cholinergic system and discuss implications for future research. Possibilities and pitfalls of targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery are also discussed.
Keywords: Acetylcholine, traumatic brain injury, nicotinic receptor, Excitotoxicity, Muscarinic and Alpha 7.
Current Pharmaceutical Design
Title:Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma
Volume: 22 Issue: 14
Author(s): Kathleen B.G. Huber, Victor V. Uteshev and James R. Pauly
Affiliation:
Keywords: Acetylcholine, traumatic brain injury, nicotinic receptor, Excitotoxicity, Muscarinic and Alpha 7.
Abstract: Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological deficits. The delayed secondary brain injury is likely to result from multiple insults including oxidative stress, mitochondrial dysfunction, breakdown of the blood brain barrier, dysregulated release of glutamate, pro-inflammatory cytokines, and other mediators. However, therapies targeting these systems have generally met with failure in clinical trials. The purpose of this review is to summarize the models used for preclinical neurotrauma research, provide a brief overview of previous failed clinical trials in head and spinal cord injury, and finally, to review involvement of the cholinergic system and discuss implications for future research. Possibilities and pitfalls of targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery are also discussed.
Export Options
About this article
Cite this article as:
Huber B.G. Kathleen, Uteshev V. Victor and Pauly R. James, Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma, Current Pharmaceutical Design 2016; 22 (14) . https://dx.doi.org/10.2174/1381612822666160127113631
DOI https://dx.doi.org/10.2174/1381612822666160127113631 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges
Current Vascular Pharmacology Sleep-Disordered Breathing and Cardiovascular Disease: Exploring Pathophysiology and Existing Data
Current Respiratory Medicine Reviews Administration of Human Umbilical Cord Blood Cells Produces Interleukin-10 (IL-10) in IL-10 Deficient Mice Without Immunosuppression
Current Stem Cell Research & Therapy Application of Mesenchymal Stem Cells in Melanoma: A Potential Therapeutic Strategy for Delivery of Targeted Agents
Current Medicinal Chemistry Design and Development of Nanovehicle-Based Delivery Systems for Preventive or Therapeutic Supplementation with Flavonoids
Current Medicinal Chemistry Glial Cells – The Key Elements of Alzheimer´s Disease
Current Alzheimer Research HIV-1-Associated Dementia During HAART Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Directed Differentiation of Pluripotent Cells Towards Therapeutic Stem Cells
Recent Patents on Regenerative Medicine Establishing Genomic/Transcriptomic Links Between Alzheimer’s Disease and Type 2 Diabetes Mellitus by Meta-Analysis Approach
CNS & Neurological Disorders - Drug Targets Prophylactic Neuroprotection
Current Drug Targets Cross-Talk between Oxidative Stress and Pro-Inflammatory Cytokines in Acute Pancreatitis: A Key Role for Protein Phosphatases
Current Pharmaceutical Design Structure and Function of Myelinated Nerve Fibers in the Rabbit Eye Following Ischemia/Reperfusion Injury
Current Neurovascular Research Colloidal Supramolecular Aggregates for Therapeutic Application in Neuromedicine
Current Medicinal Chemistry Editorial (Thematic Issue: New Therapeutic Targets in Clinical Medicine)
Current Pharmaceutical Design Anti-β-Amyloid Immunotherapy for Alzheimers Disease: Focus on Bapineuzumab
Current Alzheimer Research Role of Resveratrol and its Analogues in the Treatment of Neurodegenerative Diseases: Focus on Recent Discoveries
CNS & Neurological Disorders - Drug Targets Inflammation, High Density Lipoprotein and Endothelium
Current Medicinal Chemistry Basic and Clinical Aspects of Gene Therapy for Retinopathy Induced by Diabetes
Current Gene Therapy Bioactivities of Iridoids
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry