Elamipretide (SS-31) Improves Functional Connectivity in Hippocampus and Other Related Regions Following Prolonged Neuroinflammation Induced by Lipopolysaccharide in Aged Rats.

Liu Y, Fu H, Wu Y, Nie B, Liu F, Wang T, Xiao W, Yang S, Kan M, Fan L

Frontiers in aging neuroscience1 Mar 2021Cited by 20 (Europe PMC)

PMID33732135PMCIDPMC7956963DOI10.3389/fnagi.2021.600484PepBankPUB-33732135

Summary

Neuroinflammation has been recognized as a major cause for neurocognitive diseases. Although the hippocampus has been considered an important region for cognitive dysfunction, the influence of hippocampal neuroinflammation on brain functional connectivity (FC) has been rarely studied. In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment. Systemic and hippocampal inflammation were determined using ELISA, while astrocyte responses during hippocampal neuroinflammation were determined by interleukin 1 beta (IL-1β)/tumor necrosis factor alpha (TNFα) double staining immunofluorescence. Oxidative stress was determined by reactive oxidative species (ROS), electron transport chain (ETC) complex, and superoxide dismutase (SOD). Short- (30 days) learning and spatial working memory were tested by the Morris water maze (MWM). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus. Compared with the vehicle group, rats with the LPS exposure showed an impaired MWM performance, higher oxidative stress, higher levels of inflammatory cytokines, and astrocyte activation in the hippocampus. The neuroimaging examination showed decreased FC on the right orbital cortex, right olfactory bulb, and left hippocampus on day 3, 7, and 31, respectively, after treatment. In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance. Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment. Our study demonstrated that inhibiting neuroinflammation in the hippocampus not only reduces inflammatory responses in the hippocampus but also improves the brain FC in regions related to the hippocampus. Furthermore, early anti-inflammatory treatment with SS-31 has a long-lasting effect on reducing the impact of LPS-induced neuroinflammation.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In aged rats with LPS-induced neuroinflammation, SS‑31 treatment gave lower levels of inflammatory cytokines.
In plain wordsIn aged rats with brain inflammation, SS‑31 treatment lowered inflammatory signalling molecules.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseInflammatory cytokine levels
Study
ratn: not reported in source
Aged rats with LPS-induced neuroinflammation
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment.
Show in the study text Report a problemFND-3373213501
02AnimalAnimal study (in vivo)Efficacy outcome
In aged rats with LPS-induced neuroinflammation, SS‑31 treatment gave less astrocyte activation in the hippocampus.
In plain wordsIn aged rats with brain inflammation, SS‑31 treatment reduced activation of support cells in the memory region.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseAstrocyte activation in the hippocampus
Study
ratn: not reported in source
Aged rats with LPS-induced neuroinflammation
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment.
Show in the study text Report a problemFND-3373213502
03AnimalAnimal study (in vivo)Efficacy outcome
In aged rats with LPS-induced neuroinflammation, SS‑31 treatment improved Morris water maze performance.
In plain wordsIn aged rats with brain inflammation, SS‑31 treatment improved performance in a water maze memory test.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMorris water maze performance
Study
ratn: not reported in source
Aged rats with LPS-induced neuroinflammation
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment.
Show in the study text Report a problemFND-3373213503
04AnimalAnimal study (in vivo)Efficacy outcome
In aged rats with LPS-induced neuroinflammation, SS‑31 increased functional connectivity in the left parietal association, sensory and motor cortex on day 7 and the right flocculonodular lobe on day 31.
In plain wordsIn aged rats with brain inflammation, SS‑31 increased connectivity between some brain regions, compared with rats without SS‑31.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseFunctional connectivity (rs-fMRI) in cortex and cerebellum
Study
ratn: not reported in source
Aged rats with LPS-induced neuroinflammation
Comparator
Rats without SS-31 treatment
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus.
Summary · context
In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment.
Show in the study text Report a problemFND-3373213504

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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