Related Experiment Video

Updated: May 7, 2026

Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
08:57

Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin

Published on: March 26, 2015

Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis

Alessandra Musella1, Georgia Mandolesi, Antonietta Gentile

  • 1Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy; UOC Neurologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.

Journal of Neuroimmunology
|September 19, 2013
PubMed

Insights

Cladribine, delivered intracerebroventricularly, reduced multiple sclerosis (MS) symptoms in mice by protecting against synaptic damage. This neuroprotection occurred independently of its immunosuppressive effects.

Area of Science:

  • Neuroimmunology
  • Neuropharmacology
  • Neurophysiology

Background:

  • Multiple sclerosis (MS) involves glutamate-mediated synaptic transmission alterations.
  • Experimental autoimmune encephalomyelitis (EAE) models MS, exhibiting similar synaptic dysfunction.
  • Central nervous system inflammation in EAE impacts glutamatergic synapses.

Purpose of the Study:

  • To investigate the effects of intracerebroventricular (Icv) cladribine administration on EAE.
  • To determine if cladribine offers neuroprotection in experimental MS.
  • To elucidate the mechanism of cladribine's action on synaptic alterations in EAE.

Main Methods:

  • Intracerebroventricular (Icv) infusion of cladribine in EAE mice.
  • Assessment of clinical EAE scores.
  • Electrophysiological recordings to measure excitatory postsynaptic current (sEPSC) frequency.
  • Evaluation of microglial and astroglial activation.
  • Analysis of interleukin-1β (IL-1β) involvement.

Main Results:

  • Icv cladribine administration significantly reduced clinical deficits in EAE mice.
  • Cladribine reversed the EAE-induced enhancement of sEPSC frequency, indicating protection against glutamatergic synaptopathy.
  • Cladribine did not affect EAE-induced microglial or astroglial activation.
  • Cladribine blocked EAE synaptic alterations by interfering with interleukin-1β effects.

Conclusions:

  • Intracerebroventricular cladribine exhibits neuroprotective properties in experimental MS (EAE).
  • Cladribine's neuroprotection in EAE is mediated by interfering with IL-1β effects on synaptic function.
  • These neuroprotective effects are independent of cladribine's peripheral immunosuppressant actions.
Keywords:
CladribineEAEEPSCIL-1βMicrogliaStriatum

More Related Videos

A Stably Established Two-Point Injection of Lysophosphatidylcholine-Induced Focal Demyelination Model in Mice04:55

A Stably Established Two-Point Injection of Lysophosphatidylcholine-Induced Focal Demyelination Model in Mice

Published on: May 11, 2022

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel Disease...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...