Intravenous immunoglobulin G improves neurobehavioral and histological outcomes after traumatic brain injury in mice

Jeong, Seongtae; Lei, Beilei; Wang, Hai-Chen; Dawson, Hana N.; James, Michael L.

doi:10.1016/j.jneuroim.2014.08.626

Cited by 18 publications

(17 citation statements)

References 39 publications

(68 reference statements)

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“…IVIg is increasingly being utlized for the treatment of inflammatory/autoimmune disorders because of its potent immunomodulatory properties. IVIg therapy has already shown great promise in several models of acquired CNS injury, but this study demonstrates its robust efficacy in counteracting secondary immune‐mediated pathology in contusive SCI. We also show, for the first time, that IVIg therapy has a remarkable attenuating effect on the presence of complement activation products within the injured spinal cord, thereby providing clues as to how IVIg augments neurological recovery following neurotrauma.…”

Section: Discussionmentioning

confidence: 80%

IVIg attenuates complement and improves spinal cord injury outcomes in mice

Brennan

Kurniawan

Vukovic

et al. 2016

Ann Clin Transl Neurol

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ObjectiveTraumatic spinal cord injury (SCI) elicits immediate neural cell death, axonal damage, and disruption of the blood–spinal cord barrier, allowing circulating immune cells and blood proteins into the spinal parenchyma. The inflammatory response to SCI involves robust complement system activation, which contributes to secondary injury and impairs neurological recovery. This study aimed to determine whether intravenous immunoglobulin (IVIg), an FDA‐approved treatment for inflammatory conditions, can scavenge complement activation products and improve recovery from contusive SCI.MethodsWe used functional testing, noninvasive imaging, and detailed postmortem analysis to assess whether IVIg therapy is effective in a mouse model of severe contusive SCI.Results IVIg therapy at doses of 0.5–2 g/kg improved the functional and histopathological outcomes from SCI, conferring protection against lesion enlargement, demyelination, central canal dilation, and axonal degeneration. The benefits of IVIg were detectable through noninvasive diffusion tensor imaging (DTI), with IVIg treatment counteracting the progressive SCI‐induced increase in radial diffusivity (RD) in white matter. Diffusion indices significantly correlated with the functional performance of individual mice and accurately predicted the degree of myelin preservation. Further experiments revealed that IVIg therapy reduced the presence of complement activation products and phagocytically active macrophages at the lesion site, providing insight as to its mechanisms of action.InterpretationOur findings highlight the potential of using IVIg as an immunomodulatory treatment for SCI, and the value of DTI to assess tissue damage and screen for the efficacy of candidate intervention strategies in preclinical models of SCI, both quantitatively and noninvasively.

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Section: Discussionmentioning

confidence: 80%

IVIg attenuates complement and improves spinal cord injury outcomes in mice

Brennan

Kurniawan

Vukovic

et al. 2016

Ann Clin Transl Neurol

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“… 209 , 210 IVIG has been also examined for neuroprotective effects in ischemia-type insults. 210 , 211 , 212 In animal studies, IVIG administration acutely after SCI 213 or TBI 214 significantly improves neural functional recovery. IVIG not only suppresses the excessive immune responses via inhibiting inflammatory cytokine production, immune cell invasion/activation and complement activation in the CNS, but also reverses the concomitant immunosuppression against invading pathogens after CNS injury.…”

Section: Immunotherapy At the Adaptive Immune Response After Cns Injumentioning

confidence: 99%

Potential immunotherapies for traumatic brain and spinal cord injury

Putatunda

Bethea

2018

Chinese Journal of Traumatology

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Traumatic injury of the central nervous system (CNS) including brain and spinal cord remains a leading cause of morbidity and disability in the world. Delineating the mechanisms underlying the secondary and persistent injury versus the primary and transient injury has been drawing extensive attention for study during the past few decades. The sterile neuroinflammation during the secondary phase of injury has been frequently identified substrate underlying CNS injury, but as of now, no conclusive studies have determined whether this is a beneficial or detrimental role in the context of repair. Recent pioneering studies have demonstrated the key roles for the innate and adaptive immune responses in regulating sterile neuroinflammation and CNS repair. Some promising immunotherapeutic strategies have been recently developed for the treatment of CNS injury. This review updates the recent progress on elucidating the roles of the innate and adaptive immune responses in the context of CNS injury, the development and characterization of potential immunotherapeutics, as well as outstanding questions in this field.

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“…The observed anti-inflammatory and neuroprotective effects of IVIg were consistent with findings in a variety of another disease models. [15][16][17] The protective effects of IVIg in the optic nerve are considered to result in the prevention of clinical symptoms because of the correlation between clinical symptoms and histopathological grades. This is the first report that IVIg attenuates inflammation, demyelination and axon loss of optic nerve in mouse models.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Treatment with Intravenous Immunoglobulin Attenuates Experimental Optic Neuritis in Mice

Takahashi

Okuda

Tamura

et al. 2019

Biological & Pharmaceutical Bulletin

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Optic neuritis is characterized by optic nerve inflammation, demyelination and axonal loss. Intravenous immunoglobulin (IVIg) has been reported to be effective for steroid-resistant patients. However, there is no report investigating the histopathological efficacy of IVIg in optic neuritis models. In this study, we examined the effects of IVIg on optic neuritis of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune optic neuritis (EAON). Inflammation, demyelination and axonal loss were assessed in the optic nerve sections. IVIg showed dose-dependent prevention of clinical symptoms in EAON. IVIg provided an anti-inflammatory effect in both EAE and EAON, associated with improved demyelination. Axonal loss in EAE was also significantly attenuated. These results suggest that IVIg has neuroprotective properties in experimental optic neuritis, and is a promising new treatment for optic neuritis.

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Intravenous immunoglobulin G improves neurobehavioral and histological outcomes after traumatic brain injury in mice

Cited by 18 publications

References 39 publications

IVIg attenuates complement and improves spinal cord injury outcomes in mice

IVIg attenuates complement and improves spinal cord injury outcomes in mice

Potential immunotherapies for traumatic brain and spinal cord injury

Prophylactic Treatment with Intravenous Immunoglobulin Attenuates Experimental Optic Neuritis in Mice

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