<p>Cornel Iridoid Glycoside Protects Against White Matter Lesions Induced by Cerebral Ischemia in Rats via Activation of the Brain-Derived Neurotrophic Factor/Neuregulin-1 Pathway</p>

Abstract

BackgroundIschemic stroke often induces profound white matter lesions, resulting in poor neurological outcomes and impaired post-stroke recovery. The present study aimed to investigate the effects of cornel iridoid glycoside (CIG), a major active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke and further investigate its neuroprotective mechanisms.MethodsAdult male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) surgery for 2 h, followed by reperfusion. Rats were intragastrically administered CIG (60 mg/kg and 120 mg/kg) beginning 6 h afters reperfusion, once daily for seven days. A series of behavioral tests (modified neurological severity scores test, object recognition test, adhesive removal test, and beam walking test) were performed to evaluate the neurological functioning in MCAO rats. Histology of the white matter was studied using luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was performed to assess myelin loss, oligodendrocyte maturation, and glial activation. Activation of the brain-derived neurotrophic factor (BDNF)/neuregulin-1 (NRG1) pathway was evaluated by Western blotting.ResultsCIG treatment remarkably decreased the neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. Furthermore, CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes, and decreased the number of activated microglia and astrocytes in the corpus callosum of MCAO rats. In addition, Western blot analysis indicated that CIG increased the expression of BDNF/p-TrkB, NRG1/ErbB4 proteins, which further elevated PI3K p110α/p-Akt/p-mTOR signaling in the corpus callosum of MCAO rats.ConclusionWe demonstrated that CIG protects against white matter lesions induced by cerebral ischemia partially by decreasing the number of activated microglia and astrocytes, increasing BDNF level, and activating NRG1/ErbB4 and its downstream PI3K/Akt/mTOR pathways in the white matter. CIG might be used as a potential neuroprotective agent for the treatment of ischemic stroke.

Curcumin Ameliorates White Matter Injury after Ischemic Stroke by Inhibiting Microglia/Macrophage Pyroptosis through NF‐κB Suppression and NLRP3 Inflammasome Inhibition

“…Given the critical association between white matter injury and ischemic stroke, recent studies have focused on therapeutic strategies toward restoring white matter after stroke. A few pharmacological interventions, such as Activin A [ 30 ] and cornel iridoid glycoside [ 31 ], were shown to provide neuroprotection against ischemic stroke via promoting white matter integrity. Up to now, curcumin's neuroprotective effects have focused on stroke-induced grey matter lesions.…”

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

“…Therefore, potentiating oligodendrocyte response to ischemic damage could be a good therapeutic strategy to ameliorate cognitive and motor disabilities induced by stroke. In line with this, treatments that promote oligodendrogenesis have been shown to enhance white matter repair and to reduce ischemic damage [ 206 , 225 ]. TGF-α increases after tMCAO in neurons and glial cells including oligodendrocytes.…”

New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery

“…More recent evidence shows that intracerebral infusion of regenerative microglia-derived extracellular vesicles (EVs) restores protective microglial/macrophage functions, limiting their senescence during the post-stroke phase, and enhances the maturation of OPCs at lesion borders, resulting in ameliorated neurological functionality ( Raffaele et al, 2021 ). Cornel iridoid glycoside (CIG) treatment was reported to decrease microglial activation in the corpus callosum following stroke, accompanied with reduced white matter lesions and demyelination, increased myelin basic protein expression, and increased number of mature oligodendrocytes ( Wang et al, 2019 ).…”