ABSTRACT
Title
Omega-3 polyunsatured fatty acids attenuate the secondary inflammatory response that characterize spinal cord compression injury
Authors
Paterniti Irene
Doctorate School in Experimental Medicine
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy
Doctorate School in Experimental Medicine
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy
Abstract
Diets have changed rapidly in the past 100-150 years mainly in the type and quantity of essential fatty acids, and this is parallel to a rise in the impact of chronic diseases such as hypertension, diabetes, cardiac disease and cancer. Essential fatty acids are lipids that cannot be synthesized within the body and must be ingested through the diet or from supplements. Fish and other seafood contain long chain omega-3 polyunsatured fatty acids (ω-3 PUFAs), which are essential nutrients. Two families of essential fatty acids, omega-3 and omega-6, are required for physiological functions including oxygen transport, energy storage, cell membrane function, and regulation of inflammation and cell proliferation. Over the past 10 years, there has been increased interest in the health benefits of ω-3 PUFAs, that are vital for the normal development of the nervous system, and accumulating evidence suggests that these compounds have therapeutic potential in a variety of CNS disorders [1].The long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have significant biological effects and both have been shown to have multiple beneficial effects. DHA, in particular, is the critical component of cell membranes in the brain and retina, where it is involved in visual and neural function as well as neurotransmitter metabolism.
The aim of this study was designed to gain better insight into the mechanism of action of ω-3 PUFAs, such as DHA, in an animal model of spinal cord injury (SCI). SCI is a highly devastating pathology that occurs mainly as a consequence of road accidents, falls and acts of violence; often the neurological impairment which follows SCI could lead to catastrophic dysfunction, with significantly reduction of the quality of life not only to the individual but also to family, and impact on society.
Moreover, the pathological events following acute SCI can be divided into two chronological phases: the primary injury at the site of the impact, and the secondary injury which reflects the gradual propagation of damage over a larger area of tissue and is associated with an increase in oxidative stress, necrotic cells death and apoptotic processes.
In this model, SCI was induced in mice by the application of an aneurysm clip (force of 24 g) onto the dura mater via a four-level T5-T8 laminectomy, in order to replicate the persistence of cord compression, that is commonly observed in human SCI. This SCI in mice results in severe trauma characterized by oedema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis.
Thirty minutes after compression, animals received a tail vein injection of DHA at a dose of 500 nmol/kg (the initial stock solution was dissolved in ethanol and then diluted with physiological saline, and the final solution was adjusted to pH 7.4. All animal were killed at 24 h after SCI in order to evaluate the various parameters implicated in the development of injury.
DHA treatment significantly reduced: (1) the degree of spinal cord inflammation and tissue injury (histological score), (2) pro-inflammatory cytokine expression (TNF-α), (3) nitrotyrosine formation, (4) GFAP expression, (5) apoptosis- associated changes (FasL, Bax and Bcl-2 expression). Moreover, DHA significantly ameliorated the recovery of limb function. Our results in this in vivo study, clearly demonstrate that DHA treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma. This confirms in a mouse clip compression model of SCI the previous neuroprotective results reported with this fatty acid in rat hemisection and compression injury.
(1) Adina T. Michael-Titus (2007)- Prostaglandins, Leukotrienes and Essential Fatty Acids Vol 77, 295-300
The aim of this study was designed to gain better insight into the mechanism of action of ω-3 PUFAs, such as DHA, in an animal model of spinal cord injury (SCI). SCI is a highly devastating pathology that occurs mainly as a consequence of road accidents, falls and acts of violence; often the neurological impairment which follows SCI could lead to catastrophic dysfunction, with significantly reduction of the quality of life not only to the individual but also to family, and impact on society.
Moreover, the pathological events following acute SCI can be divided into two chronological phases: the primary injury at the site of the impact, and the secondary injury which reflects the gradual propagation of damage over a larger area of tissue and is associated with an increase in oxidative stress, necrotic cells death and apoptotic processes.
In this model, SCI was induced in mice by the application of an aneurysm clip (force of 24 g) onto the dura mater via a four-level T5-T8 laminectomy, in order to replicate the persistence of cord compression, that is commonly observed in human SCI. This SCI in mice results in severe trauma characterized by oedema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis.
Thirty minutes after compression, animals received a tail vein injection of DHA at a dose of 500 nmol/kg (the initial stock solution was dissolved in ethanol and then diluted with physiological saline, and the final solution was adjusted to pH 7.4. All animal were killed at 24 h after SCI in order to evaluate the various parameters implicated in the development of injury.
DHA treatment significantly reduced: (1) the degree of spinal cord inflammation and tissue injury (histological score), (2) pro-inflammatory cytokine expression (TNF-α), (3) nitrotyrosine formation, (4) GFAP expression, (5) apoptosis- associated changes (FasL, Bax and Bcl-2 expression). Moreover, DHA significantly ameliorated the recovery of limb function. Our results in this in vivo study, clearly demonstrate that DHA treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma. This confirms in a mouse clip compression model of SCI the previous neuroprotective results reported with this fatty acid in rat hemisection and compression injury.
(1) Adina T. Michael-Titus (2007)- Prostaglandins, Leukotrienes and Essential Fatty Acids Vol 77, 295-300