Stimulating neuroregeneration as a therapeutic drug approach for traumatic brain injury.
Traumatic brain injury, a silent epidemic of modern societies, is a largely neglected area in drug development and no drug is currently available for the treatment of patients suffering from brain trauma. Despite this grim situation, much progress has been made over the last two decades in closely related medical indications, such as spinal cord injury, giving rise to a more optimistic approach to drug development in brain trauma. Fundamental insights have been gained with animal models of central nervous system (CNS) trauma and spinal cord injury. Neuroregenerative drug candidates have been identified and two of these have progressed to clinical development for spinal cord injury patients. If successful, these drug candidates may be used to treat brain trauma patients. Significant progress has also been made in understanding the fundamental molecular mechanism underlying irreversible axonal growth arrest in the injured CNS of higher mammals. From these studies, we have learned that the axonal retraction bulb, previously regarded as a marker for failure of regenerative growth, is not static but dynamic and, therefore, amenable to pharmacotherapeutic approaches. With the development of modified magnetic resonance imaging methods, fibre tracts can be visualised in the living human brain and such imaging methods will soon be used to evaluate the neuroregenerative potential of drug candidates. These significant advances are expected to fundamentally change the often hopeless situation of brain trauma patients and will be the first step towards overcoming the silent epidemic of brain injury.
Mueller
Bernhard K
BK
Neuroscience Research, Abbott GmbH and Company KG, Ludwigshafen, Germany. bernhard.mueller@abbott.com
Mueller
Reinhold
R
Schoemaker
Hans
H
D000328:Adult; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D020439:Growth Cones / Q000187:drug effects / Q000473:pathology; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects
D002491:Central Nervous System Agents; D006131:Growth Inhibitors