Ischemic preconditioning ameliorates spinal cord ischemia-reperfusion injury by triggering autoregulation

Liang, Cheng‐Loong; Lu, Kang; Liliang, Po-Chou; Chen, Tai‐Been; Chan, Samuel H.H.; Chen, Han‐Jung

doi:10.1016/j.jvs.2011.09.096

Cited by 12 publications

(11 citation statements)

References 33 publications

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“…Previous studies demonstrate that sevoflurane can protect against ischemic neuronal damage and attenuate necrosis and apoptosis through its capacity to increase cerebral blood flow and preserve cerebral autoregulation [19]. However, few studies have attempted to describe the protective effect of this agent on spinal cord IR injury [16,20,21]. Therefore, the primary objective of this study was to investigate whether sevoflurane preconditioning can initiate protective effects on hind limb motor function and improve the viability of motor neurons in a rat model of transient aortic arch occlusion.…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats

Cao

Wang

et al. 2014

Mol Brain

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BackgroundMicroglia are the primary immune cells of the spinal cord that are activated in response to ischemia/reperfusion (IR) injury and release various neurotrophic and/or neurotoxic factors to determine neuronal survival. Among them, matrix metalloproteinase-9 (MMP-9), which cleaves various components of the extracellular matrix in the basal lamina and functions as part of the blood spinal cord barrier (BSCB), is considered important for regulating inflammatory responses and microenvironmental homeostasis of the BSCB in the pathology of ischemia. Sevoflurane has been reported to protect against neuronal apoptosis during cerebral IR. However, the effects of sevoflurane preconditioning on spinal cord IR injury remain unclear. In this study, we investigated the role of sevoflurane on potential genetic roles of microglial MMP-9 in tight junction protein breakdown, opening of the BSCB, and subsequent recruitment of microglia to apoptotic spinal cord neurons.ResultsThe results showed significant upregulation of MMP-9 in rats with IR-induced inflammation of the BSCB compared to that of the sham group, manifested as dysfunctional BSCB with increased Evans blue extravasation and reduced expression of occludin protein. Increased MMP-9 expression was also observed to facilitate invasion and migration of activated microglia, imaging as high Iba-1 expression, clustered to neurons in the injured spinal cord, as shown by double immunofluorescence, and increased proinflammatory chemokine production (CXCL10, CCL2). Further, sevoflurane preconditioning markedly improved motor function by ameliorating neuronal apoptosis, as shown by reduced TUNEL-positive cell counts and expression of cleaved caspase-3. These protective effects were probably responsible for downregulation of MMP-9 and maintenance of normal expression of occludin protein indicating BSCB integrity from inflammatory damage, which was confirmed by decreased protein levels of Iba-1 and MMP-9, as well as reduced production of proinflammatory chemokines (CXCL10, CCL2) and proinflammatory cytokines (IL-1β). Intrathecal injection of specific siRNAs targeting MMP-9 had similar protective effects to those of sevoflurane preconditioning.ConclusionsPreconditioning with 2.4% sevoflurane attenuated spinal cord IR injury by inhibiting recruitment of microglia and secretion of MMP-9; thus inhibiting downstream effects on inflammatory damage to BSCB integrity and neuronal apoptosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-014-0069-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats

Cao

Wang

et al. 2014

Mol Brain

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“…The mechanisms that have been alleged to be responsible for IPC include: (1) improving local spinal cord blood flow and tissue oxygenation [6]; (2) enhancing the binding profile of heat shock proteins [7]; and (3) suppression of apoptosis [8]. Although IPC has been shown to attenuate ischemic brain edema and cerebrovascular injury in rats [9], there are limited studies regarding the effects of IPC on blood spinal cord barrier permeability after I-R injury.…”

Section: Introductionmentioning

confidence: 99%

Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption

Fang

Sun

et al. 2013

IJMS

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Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan’s Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-α (TNF-α) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-α mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-α expression.

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“…Spinal cord I-R injury is a persistent clinical problem in surgical repair of thoracic and thoracoabdominal aneurism surgeries 19,20 . The major cause of spinal cord injury, during and after aortic surgery to the occurrence of one or more of the three following events: (I) the duration and degree of ischaemia; (II) failure to re-establish blood flow to the spinal cord after repair; (III) a biochemically mediated reperfusion injury 21 .…”

Section: Discussionmentioning

confidence: 99%

The influence of low-level laser irradiation on spinal cord injuries following ischemia- reperfusion in rats

Sotoudeh

Jahanshahi²,

Zareiy

et al. 2015

Acta Cir. Bras.

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PURPOSE:To investigate if low level laser therapy (LLLT) can decrease spinal cord injuries after temporary induced spinal cord ischemia-reperfusion in rats because of its anti-inflammatory effects. METHODS:Forty eight rats were randomized into two study groups of 24 rats each. In group I, ischemic-reperfusion (I-R) injury was induced without any treatment. Group II, was irradiated four times about 20 minutes for the following three days. The lesion site directly was irradiated transcutaneously to the spinal direction with 810 nm diode laser with output power of 150 mW. Functional recovery, immunohistochemical and histopathological changes were assessed. RESULTS:The average functional recovery scores of group II were significantly higher than that the score of group I (2.86 ± 0.68, vs 1.38 ± 0.09; p<0.05). Histopathologic evaluations in group II were showed a mild changes in compare with group I, that suggested this group survived from I-R consequences. Moreover, as seen from TUNEL results, LLLT also protected neurons from I-R-induced apoptosis in rats.CONCLUSION: Low level laser therapy was be able to minimize the damage to the rat spinal cord of reperfusion-induced injury.

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Ischemic preconditioning ameliorates spinal cord ischemia-reperfusion injury by triggering autoregulation

Abstract: IPC ameliorates spinal cord I/R injury in rats, probably mediated by triggering spinal cord autoregulation and improving local spinal cord blood flow and tissue oxygenation. This concept may be the new therapeutic targets in patients requiring aortic surgery.

Cited by 12 publications

References 33 publications

Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats

Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats

Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption

The influence of low-level laser irradiation on spinal cord injuries following ischemia- reperfusion in rats

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