Abstract
Objective: Multiple sclerosis (MS) is a debilitating neurological disorder involving an autoimmune reaction to oligodendrocytes and degeneration of the axons they ensheath in the CNS. Because the damage to oligodendrocytes and axons involves local inflammation and associated oxidative stress, we tested the therapeutic efficacy of combined treatment with a potent anti-inflammatory thalidomide analog (lenalidomide) and novel synthetic anti-oxidant cerium oxide nanoparticles (nanoceria) in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Methods: C57BL/6 mice were randomly assigned to a control (no EAE) group, or one of the four myelin oligodendrocyte glycoprotein-induced EAE groups: vehicle, lenalidomide, nanoceria, or lenalidomide plus nanoceria. During a 23. day period, clinical EAE symptoms were evaluated daily, and MRI brain scans were performed at 11-13. days and 20-22. days. Histological and biochemical analyses of brain tissue samples were performed to quantify myelin loss and local inflammation. Results: Lenalidomide treatment alone delayed symptom onset, while nanoceria treatment had no effect on symptom onset or severity, but did promote recovery; lenalidomide and nanoceria each significantly attenuated white matter pathology and associated inflammation. Combined treatment with lenalidomide and nanoceria resulted in a near elimination of EAE symptoms, and reduced white matter pathology and inflammatory cell responses to a much greater extent than either treatment alone. Interpretation: By suppressing inflammation and oxidative stress, combined treatment with lenalidomide and nanoceria can reduce demyelination and associated neurological symptoms in EAE mice. Our preclinical data suggest a potential application of this combination therapy in MS.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 151-160 |
| Number of pages | 10 |
| Journal | Experimental Neurology |
| Volume | 273 |
| DOIs | |
| State | Published - Nov 1 2015 |
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Keywords
- Cerebral ventricles
- Cerium oxide nanoparticles
- Demyelination
- EAE
- Multiple sclerosis
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience
Cite this
Combination therapy with lenalidomide and nanoceria ameliorates CNS autoimmunity. / Eitan, Erez; Hutchison, Emmette R.; Greig, Nigel H.; Tweedie, David; Celik, Hasan; Ghosh, Soumita; Fishbein, Kenneth W.; Spencer, Richard G.; Sasaki, Carl Y.; Ghosh, Paritosh; Das, Soumen; Chigurapati, Susheela; Raymick, James; Sarkar, Sumit; Chigurupati, Srinivasulu; Seal, Sudipta; Mattson, Mark P.
In: Experimental Neurology, Vol. 273, 01.11.2015, p. 151-160.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combination therapy with lenalidomide and nanoceria ameliorates CNS autoimmunity
AU - Eitan, Erez
AU - Hutchison, Emmette R.
AU - Greig, Nigel H.
AU - Tweedie, David
AU - Celik, Hasan
AU - Ghosh, Soumita
AU - Fishbein, Kenneth W.
AU - Spencer, Richard G.
AU - Sasaki, Carl Y.
AU - Ghosh, Paritosh
AU - Das, Soumen
AU - Chigurapati, Susheela
AU - Raymick, James
AU - Sarkar, Sumit
AU - Chigurupati, Srinivasulu
AU - Seal, Sudipta
AU - Mattson, Mark P.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Objective: Multiple sclerosis (MS) is a debilitating neurological disorder involving an autoimmune reaction to oligodendrocytes and degeneration of the axons they ensheath in the CNS. Because the damage to oligodendrocytes and axons involves local inflammation and associated oxidative stress, we tested the therapeutic efficacy of combined treatment with a potent anti-inflammatory thalidomide analog (lenalidomide) and novel synthetic anti-oxidant cerium oxide nanoparticles (nanoceria) in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Methods: C57BL/6 mice were randomly assigned to a control (no EAE) group, or one of the four myelin oligodendrocyte glycoprotein-induced EAE groups: vehicle, lenalidomide, nanoceria, or lenalidomide plus nanoceria. During a 23. day period, clinical EAE symptoms were evaluated daily, and MRI brain scans were performed at 11-13. days and 20-22. days. Histological and biochemical analyses of brain tissue samples were performed to quantify myelin loss and local inflammation. Results: Lenalidomide treatment alone delayed symptom onset, while nanoceria treatment had no effect on symptom onset or severity, but did promote recovery; lenalidomide and nanoceria each significantly attenuated white matter pathology and associated inflammation. Combined treatment with lenalidomide and nanoceria resulted in a near elimination of EAE symptoms, and reduced white matter pathology and inflammatory cell responses to a much greater extent than either treatment alone. Interpretation: By suppressing inflammation and oxidative stress, combined treatment with lenalidomide and nanoceria can reduce demyelination and associated neurological symptoms in EAE mice. Our preclinical data suggest a potential application of this combination therapy in MS.
AB - Objective: Multiple sclerosis (MS) is a debilitating neurological disorder involving an autoimmune reaction to oligodendrocytes and degeneration of the axons they ensheath in the CNS. Because the damage to oligodendrocytes and axons involves local inflammation and associated oxidative stress, we tested the therapeutic efficacy of combined treatment with a potent anti-inflammatory thalidomide analog (lenalidomide) and novel synthetic anti-oxidant cerium oxide nanoparticles (nanoceria) in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Methods: C57BL/6 mice were randomly assigned to a control (no EAE) group, or one of the four myelin oligodendrocyte glycoprotein-induced EAE groups: vehicle, lenalidomide, nanoceria, or lenalidomide plus nanoceria. During a 23. day period, clinical EAE symptoms were evaluated daily, and MRI brain scans were performed at 11-13. days and 20-22. days. Histological and biochemical analyses of brain tissue samples were performed to quantify myelin loss and local inflammation. Results: Lenalidomide treatment alone delayed symptom onset, while nanoceria treatment had no effect on symptom onset or severity, but did promote recovery; lenalidomide and nanoceria each significantly attenuated white matter pathology and associated inflammation. Combined treatment with lenalidomide and nanoceria resulted in a near elimination of EAE symptoms, and reduced white matter pathology and inflammatory cell responses to a much greater extent than either treatment alone. Interpretation: By suppressing inflammation and oxidative stress, combined treatment with lenalidomide and nanoceria can reduce demyelination and associated neurological symptoms in EAE mice. Our preclinical data suggest a potential application of this combination therapy in MS.
KW - Cerebral ventricles
KW - Cerium oxide nanoparticles
KW - Demyelination
KW - EAE
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=84940093278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940093278&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2015.08.008
DO - 10.1016/j.expneurol.2015.08.008
M3 - Article
C2 - 26277686
AN - SCOPUS:84940093278
VL - 273
SP - 151
EP - 160
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
ER -