TINS-1021; No. of Pages 9
Review
Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity? Adina T. Michael-Titus and John V. Priestley Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Omega-3 polyunsaturated fatty acids (PUFAs) are compounds that have a structural role in the nervous system and are essential for neurodevelopment. Results obtained with docosahexaenoic acid and eicosapentaenoic acid show therapeutic potential in neurotrauma. Traumatic brain injury (TBI) and spinal cord injury (SCI) can lead to major disability and have a significant socioeconomic cost. Thus, there is an unmet need for acute neuroprotection and for treatments that promote neuroregeneration. Acute administration of omega-3 PUFAs after injury and dietary exposure before or after injury improve neurological outcomes in experimental SCI and TBI. The mechanisms involved include decreased neuroinflammation and oxidative stress, neurotrophic support, and activation of cell survival pathways. This review raises questions that must be addressed before successful clinical translation. Traumatic neurological injury and polyunsaturated fatty acids Polyunsaturated fatty acids (PUFAs) of the omega-3 type are structural components of cell membranes. In the past decade a series of studies have unveiled an important property of these natural compounds: namely, the ability to modify the reaction of the nervous system to acute injury. Traumatic brain injury (TBI) and spinal cord injury (SCI) remain two significant challenges in neurology. These conditions predominantly affect young adults. Both types of injury are very disabling and often life changing for patients, and are associated with considerable health-care costs. A major unmet need is the provision of treatments that protect the brain and spinal cord in the acute phase, and also treatments that promote beneficial regeneration and neuroplasticity, and that lead to some restoration of function. The studies published so far indicate that omega3 PUFAs may emerge as significant contenders in this therapeutic area. This review focuses on TBI and SCI and discusses the experimental evidence of efficacy of these Corresponding author: Michael-Titus, A.T. ([email protected]). 0166-2236/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tins.2013.10.005
compounds. Translational medicine issues are highlighted, as well as key steps towards potential clinical use in neurotrauma. Traumatic brain injury and spinal cord injury — present diagnostic and management aspects Traumatic injury to the brain and spinal cord occur both in the civilian and military population. More than 10 million adults receive a TBI every year, and TBI remains the leading cause of death and disability in children and adults between 1 and 44 years of age. In civilians, traffic accidents and falls are the major causes of TBI (60% and 20–30%, respectively), followed by contact sports. Of particular concern is the frequent occurrence of repetitive mild TBI in popular sports such as rugby, hockey, boxing, wrestling, and football, and the long-term consequences for young adults affected by repetitive concussion. In armed conflicts, a major TBI cause is the blast wave induced by explosive devices [1]. Military personnel also have a high risk of SCI [2]. The ageing of the general population is changing the demographics of people affected by neurotrauma. There is an overall increase in TBI and SCI in adults over the age of 50, and in this population the mortality and morbidity associated with TBI and SCI is worse [3,4]. The management of TBI in the early minutes after injury profoundly influences outcome. Current TBI treatment guidelines put emphasis on the management of intracranial pressure, the prevention and treatment of hypotension, and adequate ventilation. No specific treatment is provided that specifically provides neuroprotection. TBI is associated with the development of long-term complications such as secondary epilepsy and chronic headaches, as well as neuropsychiatric sequelae such as anxiety and depression, cognitive dysfunction, and alterations in personality (‘post-concussion syndrome’). The management of TBI, from the medical point of view, has improved overall in the past few decades, but the associated mortality and morbidity has not improved significantly [5]. Key elements in the acute management of SCI currently include the immobilization of the patient and the surgical decompression of the spinal cord. The timing of the latter remains variable between centres worldwide; recent studies suggest that early decompression (
Review
Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity? Adina T. Michael-Titus and John V. Priestley Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Omega-3 polyunsaturated fatty acids (PUFAs) are compounds that have a structural role in the nervous system and are essential for neurodevelopment. Results obtained with docosahexaenoic acid and eicosapentaenoic acid show therapeutic potential in neurotrauma. Traumatic brain injury (TBI) and spinal cord injury (SCI) can lead to major disability and have a significant socioeconomic cost. Thus, there is an unmet need for acute neuroprotection and for treatments that promote neuroregeneration. Acute administration of omega-3 PUFAs after injury and dietary exposure before or after injury improve neurological outcomes in experimental SCI and TBI. The mechanisms involved include decreased neuroinflammation and oxidative stress, neurotrophic support, and activation of cell survival pathways. This review raises questions that must be addressed before successful clinical translation. Traumatic neurological injury and polyunsaturated fatty acids Polyunsaturated fatty acids (PUFAs) of the omega-3 type are structural components of cell membranes. In the past decade a series of studies have unveiled an important property of these natural compounds: namely, the ability to modify the reaction of the nervous system to acute injury. Traumatic brain injury (TBI) and spinal cord injury (SCI) remain two significant challenges in neurology. These conditions predominantly affect young adults. Both types of injury are very disabling and often life changing for patients, and are associated with considerable health-care costs. A major unmet need is the provision of treatments that protect the brain and spinal cord in the acute phase, and also treatments that promote beneficial regeneration and neuroplasticity, and that lead to some restoration of function. The studies published so far indicate that omega3 PUFAs may emerge as significant contenders in this therapeutic area. This review focuses on TBI and SCI and discusses the experimental evidence of efficacy of these Corresponding author: Michael-Titus, A.T. ([email protected]). 0166-2236/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tins.2013.10.005
compounds. Translational medicine issues are highlighted, as well as key steps towards potential clinical use in neurotrauma. Traumatic brain injury and spinal cord injury — present diagnostic and management aspects Traumatic injury to the brain and spinal cord occur both in the civilian and military population. More than 10 million adults receive a TBI every year, and TBI remains the leading cause of death and disability in children and adults between 1 and 44 years of age. In civilians, traffic accidents and falls are the major causes of TBI (60% and 20–30%, respectively), followed by contact sports. Of particular concern is the frequent occurrence of repetitive mild TBI in popular sports such as rugby, hockey, boxing, wrestling, and football, and the long-term consequences for young adults affected by repetitive concussion. In armed conflicts, a major TBI cause is the blast wave induced by explosive devices [1]. Military personnel also have a high risk of SCI [2]. The ageing of the general population is changing the demographics of people affected by neurotrauma. There is an overall increase in TBI and SCI in adults over the age of 50, and in this population the mortality and morbidity associated with TBI and SCI is worse [3,4]. The management of TBI in the early minutes after injury profoundly influences outcome. Current TBI treatment guidelines put emphasis on the management of intracranial pressure, the prevention and treatment of hypotension, and adequate ventilation. No specific treatment is provided that specifically provides neuroprotection. TBI is associated with the development of long-term complications such as secondary epilepsy and chronic headaches, as well as neuropsychiatric sequelae such as anxiety and depression, cognitive dysfunction, and alterations in personality (‘post-concussion syndrome’). The management of TBI, from the medical point of view, has improved overall in the past few decades, but the associated mortality and morbidity has not improved significantly [5]. Key elements in the acute management of SCI currently include the immobilization of the patient and the surgical decompression of the spinal cord. The timing of the latter remains variable between centres worldwide; recent studies suggest that early decompression (
