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J Neurotrauma. 2019 Jun 29. doi: 10.1089/neu.2019.6420. [Epub ahead of print]

A single injection of docosahexaenoic acid induces a pro-resolving lipid mediator profile in the injured tissue and a long-lasting reduction in neurological deficit after traumatic brain injury in mice.

Author information

1
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience and Trauma , 4 Newark Street , London, United Kingdom of Great Britain and Northern Ireland , E1 2AT ; o.thau-zuchman@qmul.ac.uk.
2
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience, Surgery and Trauma, London, United Kingdom of Great Britain and Northern Ireland ; r.ingram@qmul.ac.uk.
3
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience, Surgery and Trauma, London, United Kingdom of Great Britain and Northern Ireland ; gharvey4@rvc.ac.uk.
4
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience, Surgery and Trauma, London, United Kingdom of Great Britain and Northern Ireland ; t.cooke@smd13.qmul.ac.uk.
5
William Harvey Research Institute, 105713, Lipid Mediator Unit, London, London, United Kingdom of Great Britain and Northern Ireland ; f.palmas@qmul.ac.uk.
6
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience, Surgery and Trauma, London, United Kingdom of Great Britain and Northern Ireland ; p.pallier@qmul.ac.uk.
7
Barts Cancer Institute Centre for Molecular Oncology, 170818, John Vane Science Centre, London, London, United Kingdom of Great Britain and Northern Ireland ; Joseph.brook@qmul.ac.uk.
8
Barts & The London, Blizard Institute , 4 Newark Street , Whitechapel , London, United Kingdom of Great Britain and Northern Ireland , E1 2AT ; j.v.priestley@qmul.ac.uk.
9
William Harvey Research Institute, 105713, Lipid Mediator Unit, London, London, United Kingdom of Great Britain and Northern Ireland ; j.dalli@qmul.ac.uk.
10
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience, Surgery and Trauma, London, United Kingdom of Great Britain and Northern Ireland ; j.lopez-tremoleda@qmul.ac.uk.
11
Barts and The London School of Medicine and Dentistry Blizard Institute, 105711, Neuroscience, Surgery and Trauma, London, United Kingdom of Great Britain and Northern Ireland ; a.t.michael-titus@qmul.ac.uk.

Abstract

Traumatic brain injury (TBI) can lead to life-changing neurological deficits, which reflect the fast-evolving secondary injury post-trauma. There is a need for acute protective interventions, and the aim of this study was to explore in an experimental TBI model the neuroprotective potential of a single bolus of a neuroactive omega-3 fatty acid, docosahexaenoic acid (DHA), administered in a time window feasible for emergency services. Adult mice received a controlled cortical impact injury (CCI) and neurological impairment was assessed with the modified Neurological Severity Score (mNSS) up to 28 days post-injury. DHA (500 nmol/kg) or saline were injected intravenously at 30 min post-injury. The lipid mediator profile was assessed in the injured hemisphere at 3 hours post-CCI. After completion of behavioural tests and lesion assessment using magnetic resonance imaging (MRI), over 7 days or 28 days post-TBI, the tissue was analysed by immunohistochemistry. The single DHA bolus significantly reduced the injury-induced neurological deficit and increased pro-resolving mediators in the injured brain. DHA significantly reduced lesion size, the microglia and astrocytic reaction, reduced oxidation and decreased the accumulation of beta-amyloid precursor protein (APP), indicating a reduced axonal injury at 7 days post-TBI. DHA reduced the neurofilament light (NFL) levels in plasma at 28 days. Therefore, an acute single bolus of DHA post-TBI, in a time window relevant for acute emergency intervention, can induce a long-lasting and significant improvement in neurological outcome, and this is accompanied by a marked upregulation of neuroprotective mediators, including the DHA-derived resolvins and protectins.

KEYWORDS:

BIOMARKERS; METABOLISM; TRAUMATIC BRAIN INJURY; controlled cortical impact

PMID:
31256709
DOI:
10.1089/neu.2019.6420

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