Loss and recovery of the blood–nerve barrier in the rat sciatic nerve after crush injury are associated with expression of intercellular junctional proteins

Hirakawa, Hisanori; Okajima, Seiichiro; Nagaoka, Takanori; Takamatsu, Tetsuro; Oyamada, Masahito

doi:10.1016/s0014-4827(02)00035-6

Cited by 63 publications

(82 citation statements)

References 44 publications

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“…Claudin-1 is a major sealing tight junction protein, because claudin-1 KO mice are not viable because of loss of water through the skin (28). No changes of other tight junction proteins like claudin-5 and occludin were observed in our study in contrast to nerve crush injury (12). Nevertheless, other tight junction proteins might be involved as well.…”

Section: Discussioncontrasting

confidence: 49%

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Transient opening of the perineurial barrier for analgesic drug delivery

Hackel¹,

Krug

Sauer³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Selective targeting of sensory or nociceptive neurons in peripheral nerves remains a clinically desirable goal. Delivery of promising analgesic drugs is often impeded by the perineurium, which functions as a diffusion barrier attributable to tight junctions. We used perineurial injection of hypertonic saline as a tool to open the perineurial barrier transiently in rats and elucidated the molecular action principle in mechanistic detail: Hypertonic saline acts via metalloproteinase 9 (MMP9). The noncatalytic hemopexin domain of MMP9 binds to the low-density lipoprotein receptor-related protein-1, triggers phosphorylation of extracellular signal-regulated kinase 1/2, and induces down-regulation of the barrier-forming tight junction protein claudin-1. Perisciatic injection of any component of this pathway, including MMP9 hemopexin domain or claudin-1 siRNA, enables an opioid peptide ([D-Ala2, N -Me-Phe4,Gly5-ol]-enkephalin) and a selective sodium channel (NaV1.7)-blocking toxin (ProToxin-II) to exert antinociceptive effects without motor impairment. The latter, as well as the classic TTX, blocked compound action potentials in isolated nerves only after disruption of the perineurial barrier, which, in return, allowed endoneurally released calcitonin gene-related peptide to pass through the nerve sheaths. Our data establish the function and regulation of claudin-1 in the perineurium as the major sealing component, which could be modulated to facilitate drug delivery or, potentially, reseal the barrier under pathological conditions.

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Section: Discussioncontrasting

confidence: 49%

“…The tight junction proteins claudin-1, claudin-5, and occludin are expressed in the perineurium and associated with permeability changes of the perineurium in a model of crush injury of the nerve (12,13). Hypertonic solutions have been used to open barriers to enhance drug delivery to the brain (14).…”

mentioning

confidence: 99%

Transient opening of the perineurial barrier for analgesic drug delivery

Hackel¹,

Krug

Sauer³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…6 A) (Kvajo et al, 2004). The high amount of fibrin observed despite a higher level of tPA activity may be explained by the strong inhibition of thrombin by PN-1 (Baker et al, 1980;Monard, 1993;Knauer et al, 2000), which has been shown to increase after sciatic nerve injury (Friedmann et al, 1999;Hirakawa et al, 2003Hirakawa et al, , 2004. This suggests that generation of fibrin overcomes the tPA fibrinolytic effect in mice lacking PN-1.…”

Section: Discussionmentioning

confidence: 99%

Mice Lacking Protease Nexin-1 Show Delayed Structural and Functional Recovery after Sciatic Nerve Crush

Lino¹,

Atanasoski²,

Kvajo³

et al. 2007

J. Neurosci.

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Multiple molecular mechanisms influence nerve regeneration. Because serine proteases were shown to affect peripheral nerve regeneration, we performed nerve crush experiments to study synapse reinnervation in adult mice lacking the serpin protease nexin-1 (PN-1). PN-1 is a potent endogenous inhibitor of thrombin, trypsin, tissue plasminogen activators (tPAs), and urokinase plasminogen activators. Compared with the wild type, a significant delay in synapse reinnervation was detected in PN-1 knock-out (KO) animals, which was associated with both reduced proliferation and increased apoptosis of Schwann cells. Various factors known to affect Schwann cells were also altered. Fibrin deposits, tPA activity, mature BDNF, and the low-affinity p75 neurotrophin receptor were increased in injured sciatic nerves of mutant mice. To test whether the absence of PN-1 in Schwann cells or in the axon caused delay in reinnervation, PN-1 was overexpressed exclusively in the nerves of PN-1 KO mice. Neuronal PN-1 expression did not rescue the delayed reinnervation. The results suggest that Schwann cell-derived PN-1 is crucial for proper reinnervation through its contribution to the autocrine control of proliferation and survival. Thus, the precise balance between distinct proteases and serpins such as PN-1 can modulate the overall impact on the kinetics of recovery.

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“…BBB can also be compromised by drugs of abuse, such as cocaine and nicotine (Hawkins et al 2002). In the PNS, breakdown followed by recovery of the BNB after crush injury to the rat sciatic nerve are closely associated with changes in the expression of TJ proteins, such as claudin-1, claudin-5, and occludin (Hirakawa et al 2003), which in turn affect the permeability of the BNB.…”

Section: Structural Alterations and Barrier Permeability: Contributiomentioning

confidence: 99%

Neuron-Glial Interactions in Blood-Brain Barrier Formation

Banerjee

Bhat

2007

Annu. Rev. Neurosci.

176

140

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The blood brain barrier (BBB) evolved to preserve the microenvironment of the highly excitable neuronal cells to allow for action potential generation and propagation. Intricate molecular interactions between two main cell types, the neurons and the glial cells, form the underlying basis of the critical functioning of the nervous system across species. In invertebrates, interactions between neurons and glial cells are central in establishing a functional BBB. However, in vertebrates, the BBB formation and function is coordinated by interactions between neurons, glial cells, and endothelial cells. Here we review the neuron-glial interaction-based blood barriers in invertebrates and vertebrates and provide an evolutionary perspective as to how a glial-barrier system in invertebrates evolved into an endothelial barrier system. We also summarize the clinical relevance of the BBB as this protective barrier becomes disadvantageous in the pharmacological treatment of various neurological disorders.

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Loss and recovery of the blood–nerve barrier in the rat sciatic nerve after crush injury are associated with expression of intercellular junctional proteins

Cited by 63 publications

References 44 publications

Transient opening of the perineurial barrier for analgesic drug delivery

Transient opening of the perineurial barrier for analgesic drug delivery

Mice Lacking Protease Nexin-1 Show Delayed Structural and Functional Recovery after Sciatic Nerve Crush

Neuron-Glial Interactions in Blood-Brain Barrier Formation

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