Copolymer-1 Promotes Neurogenesis and Improves Functional Recovery after Acute Ischemic Stroke in Rats

Abstract

Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke.

Immunization with neural derived peptides plus scar removal induces a permissive microenvironment, and improves locomotor recovery after chronic spinal cord injury

“…Moreover, recent investigations have also shown that this strategy is capable of inducing neural restoration [15]. These beneficial effects are observed especially when INDP is administered immediately after injury.…”

“…With this in regard, studies in our laboratory have already shown that INDP promotes an in vitro and in vivo production of neurotrophic factors [13, 15]. Interestingly, it has been demonstrated that the production of this molecules could last until chronic stages of SCI [28].…”

Long noncoding RNA CDKN2B‐AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription

“…TGF-b and IL-10 are both known to be immunosuppressive cytokines (41). Cruz et al (45) have indicated the involvement of IL-4 and TGF-b in neurogenesis. The lncRNA TLRs are positively associated with the levels of IL-4, IL-10, and TGF-b (46).…”

Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

“…Immunization with Cop-1 has demonstrated to induce an increment in neurogenesis and neuron survival during acute and chronic phases of an ischemic event [101]. In the same way, Poli-Y immunomodulator has also shown an increment in cortical and hippocampal neurogenesis, as well as reduction of neural loss [88].…”