Intravenous Immunoglobulin Reduces Infarct Volume but Not Edema Formation in Acute Stroke

Abstract

Objectives: Intravenous immunoglobulin (IVIG) is used for treatment of immunodeficiencies and autoimmune disorders. Recently, IVIG has also been shown to reduce infarct size in acute stroke. Since edema treatment can provide secondary neuroprotective effects, we conducted the present study to evaluate whether edema reduction is the underlying cause of the neuroprotective properties of IVIG in experimental stroke. Methods: Male Wistar rats received either IVIG or placebo and were subjected to temporary middle cerebral artery occlusion. 24 h after temporary middle cerebral artery occlusion, clinical evaluation and 7.0T magnetic resonance imaging were performed. Ischemic lesion volume was determined on high-resolution T₂ images. T₂ relaxation time and midline shift assessed on magnetic resonance imaging as well as brain water content detected by the wet/dry method after 24 h were measured to quantify edema formation. Results: Pretreatment with IVIG leads to a statistically significant reduction of the ischemic lesion volume by 42% after 24 h, as compared to placebo treatment (p < 0.05). All three methods for quantifying edema formation indicated no differences between IVIG-treated and untreated animals (p > 0.05). Conclusion: These results suggest that the neuroprotective effect of IVIG is not an indirect result of edema reduction, but is caused by direct neuronal protection. Application of IVIG is a promising treatment concept for acute stroke. To further investigate this neuroprotective effect, studies on the efficacy, the safety profile and on the underlying mechanisms are required.

Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke

“…A high concentration of IVIg has been reported to exert protective effects in neurons during ischemic conditions. 21, 23, 24 The present results demonstrate for the first time that IVIg modulates ischemic stroke-induced NLRP1 and NLRP3 inflammasome levels, with a corresponding downregulation of the pro-inflammatory cytokines IL-1 β and IL-18.…”

“…21 The pleiotropic effects of IVIg in inhibiting multiple components of inflammation in different cell types make it an attractive candidate for use in stroke therapy. 21, 22, 23, 24 Potential effects and underlying mechanisms of IVIg on inflammasome activation in ischemic stroke-induced neuronal cell death have not been reported. In the present study, we performed a comprehensive investigation of the dynamic expression patterns of the NLRP1 and NLRP3 inflammasome in primary cortical neurons subjected to simulated ischemia, in a mouse model of focal ischemic stroke, and in brain tissue samples from stroke patients.…”

Intravenous immunoglobulin (IVIg) provides protection against endothelial cell dysfunction and death in ischemic stroke

“…We [2,3] and others [10,11] have previously demonstrated that IVIg treatment reduces brain infarct volume and mortality in experimental rodent models of stroke. This study reveals a protective effect of IVIg against endothelial dysfunction following ischemic stroke, in association with reduced leukocyte infiltration in vivo .…”

Human intravenous immunoglobulin provides protection against Aβ toxicity by multiple mechanisms in a mouse model of Alzheimer's disease

“…IVIG may serve as a potential therapy to compensate the deprivation of naturally occurring Aβ Abs in AD that would alleviate the Aβ-induced toxicity. Alternatively, IgG antibodies unrelated to specific Aβ Abs may have beneficial effects against Aβ toxicity as IgG has been shown to protect brain also against acute brain injuries [36,37]. However, the detailed mechanisms how IVIG treatment improves the AD pathology and cognitive defects are unclear.…”