Increased Serum Brain-derived Neurotrophic Factor in Multiple Sclerosis Patients on Interferon-β and Its Impact on Functional Abilities

Mehrpour, Masoud; Akhoundi, Fahimeh Haji; Delgosha, Maryam; Keyvani, Hossein; Motamed, Mohammad Reza; Sheibani, Behnam; Meysamie, Alipasha

doi:10.1097/nrl.0000000000000053

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…Our results are in agreement with a recent study showing that INF-beta can increase serum BDNF levels [27] and with a previous study demonstrating an increased production of BDNF by peripheral blood mononuclear cells following stimulation with INF-beta [28]. Serum levels of BDNF varies during to the different phases of RR-MS.…”

Section: Discussionsupporting

confidence: 93%

“…It is worth to mention also the current debate regarding the significance of serum BDNF levels in terms of biomarker of disease progression. Mehrpour et al [27], proposed serum BDNF with levels above a cut-off of 190 pg/ml as a biomarker of disease severity, while in another study, serum BDNF levels did not seem to correlate with the extent of neurodegeneration [33]. Besides the current difficulties in dissecting out the exact correlation between BDNF levels and phase or severity of the disease, our findings are in support of a possible neurotrophic effect of INF-beta in SM.…”

Section: Discussionsupporting

confidence: 56%

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Interferon-beta, but not Glatiramer Acetate treatment induces gender-specific increase in BDNF serum levels in relapsing-remitting multiple sclerosis female patients

Sartori

Metelli

Polacchini

et al. 2019

Res J Neuro N Disord

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Neuroprotection is considered a major therapeutic target in Multiple Sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). Accordingly, current disease modifying drugs (DMDs) for MS have been revaluated for their ability to stimulate production of neurotrophic factors that may provide support to neural cells against neurodegeneration. Brain-derived neurotrophic factor (BDNF) is considered the best candidate for such neuroprotective effects in MS. In the present study, we explored a potential effects of Glatiramer Acetate (GA), and Interferon-beta (IFN-b), the first two available treatments of MS, on circulating levels of BDNF considering the different BDNF forms. Using ELISA assays, we quantified mature and total BDNF in the serum of 20 relapsing-remitting MS (RR-MS) patients treated with GA and 31 with INF-beta compared with 20 age-matched RR-MS patients without any DMD. Mature BDNF but not total BDNF was significantly increased by treatment with IFN-b in female patients only, while GA had no effect. These results support a gender-specific role of BDNF in the treatment of RR-MS with INF-b. Of note, the present study was carried out with standardized ELISA assays which are commercially available and, prospectively, might be routinely used in the common clinical practice to monitor the individual response to the therapy with IFN-b.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 56%

Interferon-beta, but not Glatiramer Acetate treatment induces gender-specific increase in BDNF serum levels in relapsing-remitting multiple sclerosis female patients

Sartori

Metelli

Polacchini

et al. 2019

Res J Neuro N Disord

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“…As for beta-interferons, they were also shown to influence BDNF levels in vivo. Mehrpour et al found increased serum BDNF levels in MS patients on beta-interferons, as opposed to patients on mitoxantrone or receiving no immunotherapy [24]. Moreover, they found that higher BDNF levels were associated with smaller disability in their MS cohort.…”

Section: Discussionmentioning

confidence: 98%

Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy

Kalinowska-Łyszczarz

Pawlak

Wyciszkiewicz

et al. 2018

Neurologia i Neurochirurgia Polska

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Although neurons are the main source of neurotrophins in the healthy brain, neurotrophins can also be expressed in the immune system. We have previously shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell neurotrophin levels are associated with brain atrophy and cognitive impairment. The aim of the present study was to assess if immune-cell neurotrophin expression is impaired in MS as compared with the healthy controls, and to describe if these levels change in treatment-naïve RRMS patients, following one year of immunomodulation. Fifty treatment-naïve RRMS patients were assessed at baseline and after one year of immunomodulation (beta-interferons/glatiramer acetate). The control group included 39 healthy subjects matched according to age and gender. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA. BDNF levels were significantly lower in MS than in the healthy controls (median 613 vs. 1657pg/mg protein, p<0.001). After one year of immunomodulation, BDNF expression did not change significantly (p=0.06) on the group level. In 70% of patients there was no increase in BDNF level, and in 30% it increased. We observed no differences between treatment groups. Other neurotrophins were detected in a minority of MS samples (as opposed to the controls). To conclude, we have shown that immune-cell production of neurotrophins is impaired in MS patients. In our MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs within one year of therapy.

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“…On the other hand, other studies revealed increased serum BDNF levels in multiple sclerosis patients during interferon beta therapy [25,28,34,35]. The difference between results may be attributed to the different sample sizes, noncompliance of patients, half of our patients were in relapse, and some of them received monthly methylprednisolone.…”

Section: Discussionmentioning

confidence: 64%

Serum level of brain-derived neurotrophic factor in patients with relapsing–remitting multiple sclerosis: a potential biomarker for disease activity

Oraby

Masry

Shafy

et al. 2021

Egypt J Neurol Psychiatry Neurosurg

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Background Brain-derived neurotrophic factor (BDNF) is secreted by immune cells in response to neuroimmune and inflammatory cascades as an act to prevent axonal and neuronal damage after various pathological insults. The serum level of BDNF is altered in a diversity of neurological diseases. The aim of this work was to investigate the serum level of BDNF in patients with relapsing–remitting multiple sclerosis and the relation between BDNF and disease activity and severity. Methods A case–control study was conducted on 90 subjects: 60 patients with relapsing–remitting multiple sclerosis (30 in relapse and 30 in remission) on different lines of medical treatment and 30 healthy volunteers as a control. Clinical, functional, and radiological evaluation was done for the patients, and all the patients and controls were subjected to assessment of the serum level of BDNF by sandwich-ELISA technique. Results The BDNF level was significantly higher in MS patients in relapse than in patients in remission (P value = 0.006). In the remission group, there was no significant linear correlation between different MS patients’ characteristics and BDNF level, while in the relapse group, a positive linear correlation was found between the number of T2 infratentorial lesions and BDNF level (r = 0.402, P = 0.028). There was no statistically significant difference between the BDNF level in patients administered different drugs for MS in both remission and relapse groups (P value > 0.05). Conclusion BDNF was significantly higher in relapsing–remitting multiple sclerosis patients in the relapse phase. Attention should be paid to the link between serum BDNF level as a neuroprotective factor and multiple sclerosis; it can be a biomarker for MS activity in the near future.

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Increased Serum Brain-derived Neurotrophic Factor in Multiple Sclerosis Patients on Interferon-β and Its Impact on Functional Abilities

Abstract: This study showed a significant effect of interferon-β 1b therapy on increasing BDNF production in multiple sclerosis.

Cited by 12 publications

References 27 publications

Interferon-beta, but not Glatiramer Acetate treatment induces gender-specific increase in BDNF serum levels in relapsing-remitting multiple sclerosis female patients

Interferon-beta, but not Glatiramer Acetate treatment induces gender-specific increase in BDNF serum levels in relapsing-remitting multiple sclerosis female patients

Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy

Serum level of brain-derived neurotrophic factor in patients with relapsing–remitting multiple sclerosis: a potential biomarker for disease activity

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