Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury

Muramoto, Akio; Imagama, Shiro; Natori, Takahiro; Wakao, Norimitsu; Ando, Kei; Tauchi, Ryoji; Hirano, Ken‐ichi; Shinjo, Ryuichi; Matsumoto, Tomohiro; Ishiguro, Naoki; Kadomatsu, Kenji

doi:10.1016/j.neulet.2013.06.025

Cited by 21 publications

(28 citation statements)

References 25 publications

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“…In the central nervous system (CNS), the role of MK in inflammation is poorly understood. It has been shown that this cytokine is not involved in the development of astrogliosis or activation of microglia in a spinal cord injury model [17]. However, MK is found highly upregulated in pathologies characterized by inflammation such as cerebral infarction and neurodegenerative diseases [18, 19] and in different brain areas after administration of drugs of abuse [20].…”

Section: Introductionmentioning

confidence: 99%

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Vicente-Rodríguez

Fernández-Calle

Gramage

et al. 2016

Mediators of Inflammation

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Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK.

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Section: Introductionmentioning

confidence: 99%

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Vicente-Rodríguez

Fernández-Calle

Gramage

et al. 2016

Mediators of Inflammation

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“…Glial scars are composed essentially of reactive astrocytes and the ECM, and have long been regarded as a major obstacle to axon regeneration [1,4,5,10,11]. CSPGs, mostly secreted by reactive astrocytes, represent one of the main inhibitory components of the ECM [4,5,16].…”

Section: Discussionmentioning

confidence: 99%

“…CSPGs, mostly secreted by reactive astrocytes, represent one of the main inhibitory components of the ECM [4,5,16]. Previous studies focused either on the astrocytes or the inhibitory molecule, and few experiments involved in the two key elements of glial scar.…”

Section: Discussionmentioning

confidence: 99%

“…Chondroitin sulfate proteoglycans (CSPGs) are one of the most important extracellular matrix (ECM) components of glial scar, and are regarded as the key inhibitory molecules in axon regeneration [4,5]. This macromolecule consists of a core protein and a variable number of glycosaminoglycans (GAG) side chains.…”

Section: Introductionmentioning

confidence: 99%

“…Reactive astrocytes profusely re-express vimentin, and persistently secrete CSPGs after injury [2,4,5,9]. The meshwork of interwoven astrocytic processes and the inhibitory CSPG molecules in the ECM form a mechanical and biochemical barrier to axon regrowth [1,4,5,11]. CSPGs and CSPGs-producing cells are both key elements in glial scar formation, which could inhibit regenerative processes through changes in the diffusion of molecules in the extracellular space [11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antisense vimentin cDNA combined with chondroitinase ABC promotes axon regeneration and functional recovery following spinal cord injury in rats

Xia

Yan

Xia

et al. 2015

Neuroscience Letters

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Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury

Manley¹,

Priest

Denham

et al. 2017

Stem Cells Translational Medicine

102

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Cervical spinal cord injury (SCI) remains an important research focus for regenerative medicine given the potential for severe functional deficits and the current lack of treatment options to augment neurological recovery. We recently reported the preclinical safety data of a human embryonic cell-derived oligodendrocyte progenitor cell (OPC) therapy that supported initiation of a phase I clinical trial for patients with sensorimotor complete thoracic SCI. To support the clinical use of this OPC therapy for cervical injuries, we conducted preclinical efficacy and safety testing of the OPCs in a nude rat model of cervical SCI. Using the automated TreadScan system to track motor behavioral recovery, we found that OPCs significantly improved locomotor performance when administered directly into the cervical spinal cord 1 week after injury, and that this functional improvement was associated with reduced parenchymal cavitation and increased sparing of myelinated axons within the injury site. Based on large scale biodistribution and toxicology studies, we show that OPC migration is limited to the spinal cord and brainstem and did not cause any adverse clinical observations, toxicities, allodynia, or tumors. In combination with previously published efficacy and safety data, the results presented here supported initiation of a phase I/IIa clinical trial in the U.S. for patients with sensorimotor complete cervical SCI. STEM CELLS

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Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury

Cited by 21 publications

References 25 publications

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Antisense vimentin cDNA combined with chondroitinase ABC promotes axon regeneration and functional recovery following spinal cord injury in rats

Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury

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