The acute administration of eicosapentaenoic acid is neuroprotective after spinal cord compression injury in rats

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Abstract

The aim of the present study was to investigate the effects of treatment with eicosapentaenoic acid (EPA) after spinal cord compression injury in adult rats. Saline or EPA (250 nmol/kg) was administered intravenously 30 min after compression injury. Locomotor recovery was assessed daily using the BBB open-field locomotor score. One week after injury, animals were sacrificed and the spinal cord tissue containing the compression epicenter, and the adjacent rostral and caudal segments, was immunostained using specific markers for neurons, oligodendrocytes, axonal injury, and macrophages/microglia. Administration of EPA resulted in decreased axonal injury and increased neuronal and oligodendrocyte survival, in the lesion epicenter and adjacent tissue. The behavioural assessment mirrored the neuroprotective effects and showed a significantly improved functional recovery in animals treated with EPA compared to the saline-treated controls over the 7-day period. These observations suggest that EPA has neuroprotective properties when administered after spinal cord trauma.

Introduction

Spinal cord injury (SCI) is a catastrophic event which can result in permanent disability. Currently there are no effective treatments, although intensive rehabilitation can facilitate some recovery of function. Major progress has been made in preclinical studies on neuroprotection and regeneration [17], [26], but this progress has not yet been translated to the clinic.

We have previously shown that the omega-3 polyunsaturated fatty acids (PUFAs) α-linolenic acid and docosahexaenoic acid (DHA) confer potent neuroprotection following hemisection and compression SCI in rats [14], [16]. Eicosapentaenoic acid (EPA), a biosynthetic precursor of DHA, has also been shown to have anti-inflammatory and neuroprotective properties in animal models of neuroinflammation [29], and has recently been reported to improve the prognosis after subarachnoid haemorrhage in patients [31]. It is important to identify whether any therapeutic benefit for SCI may be obtained through EPA administration. We have carried out a preliminary investigation of the effects of acute treatment with EPA in a rat compression SCI model [13], tested at the same dose chosen for our DHA studies. We monitored the locomotor outcome and examined neuronal and oligodendrocyte survival, axonal injury and the inflammatory reaction, in the lesion epicenter and adjacent tissue.

Section snippets

Preparation of EPA

1 M stock aliquots of EPA free fatty acid (Sigma, Dorset, UK) were prepared under 100% nitrogen and were made up in absolute ethanol. 5 μl stock aliquots were kept at −20 °C in light sensitive, airtight glass containers (Agilent, Stockport, UK) to prevent oxidation. On the day of surgery, solutions were diluted to the required concentration (250 nmol/kg body weight; injection volume 5 ml/kg) with physiological saline (NaCl 0.9%), and adjusted to pH 7.4.

Animals and compression SCI

All animal procedures were approved by the

Neuronal survival

Examination of NeuN labeling at 7 days post-injury showed that animals that received an EPA injection 30 min after injury had substantially more labeled cells in the dorsal horns (Fig. 1b and e) and ventral horns in the epicenter compared to saline-injected controls. Quantitative analyses confirmed these differences, with animals receiving EPA resulting in significantly more NeuN labeled cells in the compression epicenter than saline controls in the dorsal horns (673±90 vs. 406±66; P<0.05; Fig. 1

Discussion and conclusions

This study demonstrates for the first time that EPA is neuroprotective in spinal cord trauma. Intravenous administration of EPA 30 min after compression SCI resulted in decreased axonal injury, and increased neuronal and oligodendrocyte survival, in the lesion epicenter. The neuroprotective effect of EPA was also seen rostrally and caudally to the compression site, supporting the idea that EPA reduced the extent of secondary damage. Furthermore, the BBB scores showed a significantly improved

Conflict of interest statement

None of the authors has any conflict of interest related to this study.

Acknowledgement

We gratefully acknowledge support from the Corporate Action Trust, UK and Chang Gung Memorial Hospital, Taiwan (CMRPG360621)

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