Receptor-mediated transport of LIF across blood–spinal cord barrier is upregulated after spinal cord injury

Pan, Weihong; Cain, Courtney; Yu, Yongmei; Kastin, Abba J.

doi:10.1016/j.jneuroim.2006.02.006

Cited by 42 publications

(28 citation statements)

References 21 publications

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“…It suggests that both barrier disruption and an upregulated transport system were involved in the influx of leptin from blood to brain. Similar regulatory changes have been seen with other polypeptide cytokines in mouse models of autoimmune encephalomyelitis (Pan et al, 1996), brain and spinal cord injury (Pan et al, 1997(Pan et al, , 2006a, and stroke (Pan et al, 2006b). As the blood concentration of leptin was significantly reduced in mice with chronic alcohol intoxication, the greater permeability of the BBB to leptin may serve to prevent further reduction of brain leptin concentrations to a premorbid level.…”

Section: Discussionmentioning

confidence: 58%

Increased Leptin Permeation across the Blood–Brain Barrier after Chronic Alcohol Ingestion

Pan

Barron

Hsuchou

et al. 2007

Neuropsychopharmacol

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Leptin, a polypeptide mainly produced in the periphery, crosses the blood-brain barrier (BBB) by receptor-mediated transport to exert multiple central nervous system actions including decreased food intake. The reciprocal interactions between leptin transport and alcohol drinking are not clear. In this study, we tested whether alcohol increases leptin entry into brain and, if this occurs, whether it is a consequence of a generalized increase in the permeability of the BBB. BBB permeability to albumin, the increased permeation of which indicates BBB disruption, as well as to leptin was measured after alcohol ingestion. CD1 and B6 mice ingested a 5% liquid alcohol diet or its isocaloric control for 2 weeks. Alcohol ingestion resulted in increased blood-alcohol levels, decreased blood-leptin concentrations, and increased permeation of radioactively labeled leptin across the BBB as shown by in situ perfusion. Although the increased influx of the vascular marker albumin into brain showed partial disruption of the BBB, the influx of 125 I-leptin still could be suppressed by excess unlabeled leptin, indicating persistence of its saturable transport system. When given a choice of either alcohol or control diet, even the alcohol-preferring B6 mice showed a significantly greater preference for the control liquid diet, and there was no evidence of BBB disruption or alterated leptin transport. Furthermore, acute alcohol intoxication induced by intraperitoneal injection of 20% alcohol did not result in BBB disruption or increased leptin permeation 4 h later. Thus, partial disruption of the BBB and increased permeation of leptin in both CD1 and B6 mice were only induced by chronic alcohol ingestion. The results showing increased leptin permeation across the BBB lead to the speculation that leptin may serve as a homeostatic feeding signal in these mice.

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Section: Discussionmentioning

confidence: 58%

Increased Leptin Permeation across the Blood–Brain Barrier after Chronic Alcohol Ingestion

Pan

Barron

Hsuchou

et al. 2007

Neuropsychopharmacol

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“…The lumbar spinal cord/serum ratio of 125 I-LIF 10 min after intravenous injection of the radiotracer was significantly higher in the SCI mice than the controls [41], This increase was suppressed in the presence of excess unlabeled LIF or the blocking antibody against LIFR, neither of which affected the entry of albumin. The enhanced transport of LIF correlated with increased expression of LIFR, but not its non-selective gp130 receptor, as shown by immunofluorescent staining and western blot [41], Thus, like TNF but apparently unlike BDNF and IGF1, the receptors for LIF are crucial for the regulatory function of the BSCB in SCI.…”

Section: B Upregulation Of Lif Transportmentioning

confidence: 81%

“…In another study in normal mice, entry of LIF into spinal cord was decreased by inclusion of a polyclonal antibody directed against the extracellular domain of the specific gp190 receptor for LIF (LIFR) but not by a control antibody against the EGF receptor [33]. In vitro in RBE4 cells, both excess LIF and the LIF antibody significantly decreased the permeability coefficient.…”

Section: Leukemia Inhibitory Factor (Lif) In Sci 4a Lif Transport Inmentioning

confidence: 99%

Cytokine Transport Across the Injured Blood-Spinal Cord Barrier

Pan¹,

Kastin²

2008

CPD

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Spinal cord injury (SCI) induces dynamic changes of the blood-spinal cord barrier and even the more distant blood-brain barrier. Besides an immediate increase of paracellular permeability resulting from the direct impact of the injury, the transport systems for selective cytokines undergo regulatory changes. Since many of the transported molecules play essential roles in neuroregeneration, we propose that this altered peripheral tissue / CNS interaction benefits remodeling of the spinal cord and functional recovery after SCI. This review examines the transport of cytokines and neurotrophic factors into the spinal cord, emphasizing the upregulation of two cytokines -tumor necrosis factor α (TNF) and leukemia inhibitory factor (LIF) -during the course of SCI. The increased transport of TNF and LIF after SCI remains saturable and does not coincide with generalized BBB disruption, highlighting a pivotal regulatory role for the bloodspinal cord barrier.

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“…Leukemia inhibitory factor (LIF) belongs to the IL-6 family of cytokines and in vitro studies suggest that LIF enhances OPC differentiation [112]. Receptor-mediated LIF transport across spinal cord blood vessels has been detected during the first week postinjury [113]; therefore, endogenous systemic LIF may contribute to OPC differentiation after SCI. Another well-described cytokine is transforming growth factor (TGF)β1, which is significantly increased, along with its receptors, after SCI in rodents and humans [114][115][116].…”

Section: To Be or Not To Be: Opcs To Olsmentioning

confidence: 99%

Oligodendrocyte Fate after Spinal Cord Injury

2011

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Summary: Oligodendrocytes (OLs) are particularly susceptible to the toxicity of the acute lesion environment after spinal cord injury (SCI). They undergo both necrosis and apoptosis acutely, with apoptosis continuing at chronic time points. Loss of OLs causes demyelination and impairs axon function and survival. In parallel, a rapid and protracted OL progenitor cell proliferative response occurs, especially at the lesion borders. Proliferating and migrating OL progenitor cells differentiate into myelinating OLs, which remyelinate demyelinated axons starting at 2 weeks postinjury. The progression of OL lineage cells into mature OLs in the adult after injury recapitulates development to some degree, owing to the plethora of factors within the injury milieu. Although robust, this endogenous oligogenic response is insufficient against OL loss and demyelination. First, in this review we analyze the major spatial-temporal mechanisms of OL loss, replacement, and myelination, with the purpose of highlighting potential areas of intervention after SCI. We then discuss studies on OL protection and replacement. Growth factors have been used both to boost the endogenous progenitor response, and in conjunction with progenitor transplantation to facilitate survival and OL fate. Considerable progress has been made with embryonic stem cellderived cells and adult neural progenitor cells. For therapies targeting oligogenesis to be successful, endogenous responses and the effects of the acute and chronic lesion environment on OL lineage cells must be understood in detail, and in relation, the optimal therapeutic window for such strategies must also be determined.

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Receptor-mediated transport of LIF across blood–spinal cord barrier is upregulated after spinal cord injury

Cited by 42 publications

References 21 publications

Increased Leptin Permeation across the Blood–Brain Barrier after Chronic Alcohol Ingestion

Increased Leptin Permeation across the Blood–Brain Barrier after Chronic Alcohol Ingestion

Cytokine Transport Across the Injured Blood-Spinal Cord Barrier

Oligodendrocyte Fate after Spinal Cord Injury

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