Therapeutic spectrum of interferon‐β in ischemic stroke

Abstract

Ischemic stroke is devastating and a major cause of morbidity and mortality worldwide. To date, only clot retrieval devices and/or intravenous tissue plasminogen activators (tPA) have been approved by the US-FDA for the treatment of acute ischemic stroke. Therefore, there is an urgent need to develop an effective treatment for stroke that can have limited shortcomings and broad spectrum of applications.Interferon-beta (IFN-β), an endogenous cytokine and a key anti-inflammatory agent, contributes toward obviating deleterious stroke outcomes. Therefore, exploring the role of IFN-β may be a promising alternative approach for stroke intervention in the future. In the present review, we have discussed about IFN-β along with its different mechanistic roles in ischemic stroke. Furthermore, therapeutic approaches targeting the inflammatory cascade with IFN-β therapy that may be helpful in improving stroke outcome are also discussed. K E Y W O R D S Anti-inflammatory, cytokines, IFNβ, stroke | 117 WANVE et al. How to cite this article: Wanve M, Kaur H, Sarmah D, et al. Therapeutic spectrum of interferon-β in ischemic stroke.

Endoplasmic reticulum–mitochondria crosstalk: from junction to function across neurological disorders

“…In cerebral ischemia, ER stress and mitochondrial dysfunctions are among the main pathological events taking place . While specific involvement of the ER and mitochondria in cerebral ischemia remains unclear, according to recent reports ER stress is a key factor in mitochondrial dysfunction . Excessive Ca 2+ release from both IP3Rs and RyRs of the ER causes Ca 2+ overload in mitochondria and triggers apoptosis .…”

Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes

“… 40 , 41 The miR-576-3p has been reported to induce interferon production, and gene therapy to restore interferon production may improve prognosis after ischemic stroke. 42 , 43 The miR-665 is down-regulated in T2DM patients and up-regulated in stroke patients. 44 , 45 This suggests that the four miRNAs that we identified – especially miR-576-3p, with the most target genes – may be risk factors and markers for the development of ischemic stroke in T2DM patients.…”

Thinking Outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke

“…Regulation of numerous pathways involved in physiological cellular death and survival, activated after pathogenic injury, inducing the production of many cytokines [20,21] Glatiramer acetate Copaxone, Teva Subcutaneous Development of protective autoimmunity, activation of immunomodulatory functions of helper and regulatory T cells, shift in the production of cytokines to an anti-inflammatory phenotype, induction of pro-neurogenic factors [22,23] Teriflunomide Aubagio, Sanofi-Aventis Oral Selective inhibition of dihydro-orotate dehydrogenase, hindering the proliferation of activated B and T lymphocytes, and their migration into the CNS [24] Dimethyl fumarate Tecfidera, Biogen Oral Alteration in the composition of leukocyte subgroups, shifting their phenotype to anti-inflammatory, induction of T-cell apoptosis, downregulation of adhesion molecules and blocking of leucocyte permeation through the brain-blood barrier (BBB) [25] * Central nervous system. ** Sphingosine-1-phosphate.…”

“…Interferon beta (IFN-b) (Rebif, Merck Serono, Darmstadt, Germany, and Avonex, Genesis Pharma, Athens, Greece) is an endogenous cytokine of the interferon family, which is involved in immune reactions against viral infections, stimulating numerous pathways that promote physiological cellular death or survival [20]. IFN-b responds to pathogenic injury and activates a wide array of cytokines; it has been used as an effective treatment for RRMS, thought to act on inducing anti-inflammatory pathways, reducing cell trafficking via the BBB, and promoting neuronal repair [21].…”

“…IFN-b responds to pathogenic injury and activates a wide array of cytokines; it has been used as an effective treatment for RRMS, thought to act on inducing anti-inflammatory pathways, reducing cell trafficking via the BBB, and promoting neuronal repair [21]. Due to its versatile anti-inflammatory and cell-regulating properties, it is hypothesized to be potentially beneficial also in the setting of IS [20].…”