Related Experiment Video
Updated: Jan 4, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
The temporal and causal relationship between inflammation and neurodegeneration in multiple sclerosis
Ron Milo1, Amos D Korczyn2, Navid Manouchehri3
1Department of Neurology, Barzilai Medical Center, Ashkelon, Israel/Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel.
Abstract:
It is currently incompletely understood whether inflammation and neurodegeneration are causally related in multiple sclerosis (MS). The sequence of a potential causal relationship is also unknown. Inflammation is present in rather all clinical stages of MS. Its role in the pathogenesis of MS is supported by histopathological analyses, genetic data, and numerous animal models of MS. All approved disease-modifying therapies that reduce clinical relapses and diminish the accumulation of lesions on neuroimaging are anti-inflammatory. Axonal loss and accelerated brain volume loss can also be detected from clinical disease onset throughout all stages. The expression of neurofilament light chain in cerebrospinal fluid and serum, a scaffolding protein in axons and dendrites, is a biomarker of neuronal injury associated with clinical relapses and reflects neuronal loss during episodes of acute inflammation. The recent association of human endogenous retrovirus (HERV) and its envelope proteins with MS illustrates a pathogenic pathway that causally links central nervous system (CNS)-intrinsic proinflammatory effects and inhibition of myelin repair and neuroregeneration. A review of current data on the causal relationship between inflammation and neurodegeneration in MS identified numerous plausible pathomechanisms that link the two events. Observations from most experimental models appear to favor a pathogenesis in which inflammation precedes neurodegeneration.
Insights
Inflammation likely precedes neurodegeneration in multiple sclerosis (MS). Current therapies target inflammation, and new research links human endogenous retroviruses (HERVs) to MS pathogenesis.
Area of Science:
- Neuroimmunology
- Neurobiology
- Pathogenesis of Multiple Sclerosis
Background:
- The causal relationship and sequence between inflammation and neurodegeneration in multiple sclerosis (MS) remain incompletely understood.
- Inflammation is a hallmark across all clinical stages of MS, supported by histopathology, genetics, and animal models.
- Current MS therapies primarily target inflammation, reducing relapses and lesion accumulation.
Purpose of the Study:
- To review current data on the causal relationship between inflammation and neurodegeneration in MS.
- To explore potential pathomechanisms linking inflammation and neurodegeneration.
- To determine the sequence of events in MS pathogenesis.
Main Methods:
- Review of existing literature and experimental data on MS pathogenesis.
- Analysis of histopathological findings, genetic data, and animal models.
- Examination of biomarkers such as neurofilament light chain and novel associations like human endogenous retroviruses (HERVs).
Main Results:
- Numerous plausible pathomechanisms linking inflammation and neurodegeneration in MS have been identified.
- Neurofilament light chain expression indicates neuronal injury associated with acute inflammation.
- Recent findings suggest a pathway involving HERV envelope proteins, linking CNS inflammation to impaired myelin repair and neuroregeneration.
Conclusions:
- Evidence suggests inflammation precedes neurodegeneration in MS pathogenesis.
- Understanding this causal link is crucial for developing effective neuroprotective strategies.
- Targeting inflammation and novel pathways like HERV involvement may offer therapeutic benefits.
