Therapeutic Ef fi cacy of Erythropoietin in Experimental Autoimmune Encephalomyelitis in Mice, a Model of Multiple Sclerosis - Tissue-Protective Cytokines: Methods and Protocols - page 159

Chapter 10

Therapeutic Efficacy of Erythropoietin
in Experimental Autoimmune Encephalomyelitis
in Mice, a Model of Multiple Sclerosis

Ilaria Cervellini , Pietro Ghezzi , and Manuela Mengozzi

Abstract

Erythropoietin (EPO) has neuroprotective effects in many models of damage and disease of the nervous
system where neuroinflammation plays a substantial role, including experimental autoimmune encephalo-
myelitis (EAE), the animal model of multiple sclerosis (MS). Since the first pioneering studies, in which
EPO was shown to protect rats with acute EAE mainly by inhibiting inflammation, many other studies
have pointed out other mechanisms of protection, including oligodendrogenesis and inhibition of axonal
damage.
Here we review the preclinical studies in which EPO has shown therapeutic efficacy in several models
of EAE in mice and rats. Moreover, we report in detail the protocol to administer EPO to mice with
myelin oligodendrocyte glycoprotein (MOG)-induced chronic progressive EAE, and a representative
result. In this model, EPO inihibits the clinical score of the disease when administered according to a pre-
ventive but also to a therapeutic schedule, and therefore at disease onset, suggesting that it might not only
inhibit inflammation but also actively stimulate repair.

Key words Neuroinflammation, Demyelination, Neuroprotection, Animal model, Myelin
oligodendrocyte glycoprotein

1 Introduction

Several therapies can slow down disease progression, but to date
there is no cure for multiple sclerosis (MS), and patients suffer
from progressive neurological disability. Most treatment options
target the immune system, inhibiting the autoimmune response
and the associated inflammation, but are not able to reverse axonal
damage, the main cause of permanent disability (reviewed in ( 1 )).
Classical neuroprotective and neurotrophic factors, like brain
derived neurotrophic factor (BDNF), have been difficult to admin-
ister because they hardly penetrate the blood-brain barrier ( 2 ).
A neuroprotective neuroregenerative strategy is still needed.