Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation.

Abstract

BACKGROUND:

Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage.

METHODS:

By using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO).

RESULTS:

SSO significantly reduced the lipopolysaccharide/interferon-γ-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α, and the protein levels of inflammatory enzymes including nitric oxide synthase 2, cyclooxygenase-2 (COX-2), and p38 mitogen-activated protein kinase (MAPK) in microglia, without causing cell toxicity. Although SSO failed to directly alleviate glutamate-induced excitotoxicity in murine cortical neurons, it prevented inflammation-induced neuronal death in microglia-neuron co-cultures. Importantly, oral administration of SSO in Balb/c mice subjected to permanent occlusion of the middle cerebral artery reduced microglial activation in the peri-ischemic area and attenuated brain damage. This in vivo neuroprotective effect of SSO was associated with a reduction in the COX-2 and heme oxygenase-1 immunoreactivities.

CONCLUSIONS:

Our results suggest that SSO is an anti-inflammatory and a possible therapeutic candidate in diseases such as stroke where inflammation is a central hallmark.

• Authors: Hiramani Dhungana, Mikko T Huuskonen, Merja Jaronen, Sighild Lemarchant, Humair Ali, Velta Keksa-Goldsteine, Gundars Goldsteins, Katja M Kanninen, Jari Koistinaho, Tarja Malm
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 14 Issue 1 Pg. 237 (Dec 04 2017) ISSN: 1742-2094 [Electronic] England
• PMID: 29202856 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Oleic Acids

Topics

• Animals
• Cells, Cultured
• Inflammation (etiology, pathology)
• Mice
• Neuroprotective Agents (pharmacology)
• Oleic Acids (pharmacology)
• Stroke (complications, pathology)