Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury

Hsu, Jung Yu C.; McKeon, Robert J.; Goussev, Staci; Werb, Zena; Lee, Jung Uek; Trivedi, Alpa; Noble-Haeusslein, Linda J.

doi:10.1523/jneurosci.1993-06.2006

Cited by 204 publications

(195 citation statements)

References 76 publications

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“…In the context of SCI, this observation is relevant because MMP-2 promotes functional recovery after SCI by regulating glial scar formation. 4 Notably, the previously reported regulation of microtubule dynamics through STAT3 interaction with stathmin was not observed in astrocytes in our study, as the microtubule cytoskeleton of STAT3-cKO astrocytes was unaltered. Further examination of the mechanisms through which STAT3 regulates reactive astrocyte dynamics revealed a critical role for the small GTPase RhoA, a key regulator of actin dynamics.…”

contrasting

confidence: 63%

STAT3-regulated RhoA drives reactive astrocyte dynamics

Raffi

2017

Cell Cycle

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contrasting

confidence: 63%

STAT3-regulated RhoA drives reactive astrocyte dynamics

Raffi

2017

Cell Cycle

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“…TAPI inhibits TNF-α activation by chelating TNF-α converting enzyme (TACE) and, at higher doses, MMP-9 and other MMPs. MMP inhibition also improves electrophysiologic nerve conduction and motor performance (Leppert et al, 1999;Hsu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

Chattopadhyay

Myers

Janes

et al. 2007

Brain, Behavior, and Immunity

122

113

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Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is induced in Schwann cells hours after peripheral nerve injury and controls axonal degeneration and macrophage recruitment to the lesion. Here, we report a robust (90-fold) increase in MMP-9 mRNA within 24 h after rat sciatic nerve crush (1 to 60 days time-course). Using direct injection into a normal sciatic nerve, we identify the proinflammatory cytokines TNF-α and IL-1β as potent regulators of MMP-9 expression (Taqman qPCR, zymography). Myelinating Schwann cells produced MMP-9 in response to cytokine injection and crush nerve injury. MMP-9 gene deletion reduced unstimulated neuropathic nociceptive behavior after one week post-crush and preserved myelin thickness by protecting myelin basic protein (MBP) from degradation, tested by Western blot and immunofluorescence. These data suggest that MMP-9 expression in peripheral nerve is controlled by key proinflammatory cytokine pathways, and that its removal protects nerve fibers from demyelination and reduces neuropathic pain after injury.

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“…All experimental procedures attempted to minimize the suffering of the experimental rats. The SCI model was established as described previously (12). Briefly, the experimental rats were anesthetized with intraperitoneal injection of sodium pentobarbital (50 mg/kg; Sigma-Aldrich; Merck KGaA, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK

Wang

Zhu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Geraniol is a type of monoterpenoid with a rose scent and a slightly sweet flavor. It is found in the volatile oil of various plants, and has anti-inflammatory and anti-oxidant effects. The present study aimed to investigate the protective effect of geraniol in inhibiting the inflammatory response, oxidative stress and apoptosis in traumatic spinal cord injury (SCI), as well as to analyze the mechanism underlying its effect. Adult male Sprague-Dawley rats were induced to traumatic SCI through a surgical procedure and were defined as the SCI model group. SCI or normal rats were then administered 250 mg/kg/day geraniol for 4 weeks. The Basso, Beattie and Bresnahan (BBB) test and the spinal cord water content were used to analyze the effect of geraniol against traumatic SCI in rats. The inflammatory response, oxidative stress, and caspase-9 and -3 activities were measured using commercial ELISA kits. In addition, the associated mechanism was analyzed, using western blot analysis to determine the protein expression levels of nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). The results of the present study demonstrated that BBB scores were significantly increased and the spinal cord water content was significantly inhibited in SCI rats after 3 weeks of geraniol treatment. Furthermore, the inflammatory response, oxidative stress, and the caspase-9 and -3 activities were significantly suppressed upon treatment with geraniol. Finally, the mechanism of geraniol against traumatic SCI downregulated the NF-κB and p38 MAPK pathways in SCI rats. Therefore, the protective effect of geraniol is suggested to inhibit the inflammatory response, oxidative stress and apoptosis in traumatic SCI through the modulation of NF-κB and p38 MAPK.

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Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury

Cited by 204 publications

References 76 publications

STAT3-regulated RhoA drives reactive astrocyte dynamics

STAT3-regulated RhoA drives reactive astrocyte dynamics

Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK

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