A Bradykinin BK2 Receptor Antagonist HOE-140 Attenuates Blood-Spinal Cord Barrier Permeability Following a Focal Trauma to the Rat Spinal Cord

Sharma, Hari Shanker

doi:10.1007/978-3-7091-6346-7_32

Cited by 14 publications

(22 citation statements)

References 17 publications

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“…Bradykinin antagonists attenuate BSCB permeability following SCI [115,116]; clinically, these agents also reduce neurological impairment after closed head injury, suggesting that bradykinin inhibition is a key mechanism for neuroprotection [112,113]. An interesting clinical use of the nonapeptide concerns pharmacological preconditioning to induce bradykinin tolerance in nerve tissue.…”

Section: Bradykininmentioning

confidence: 97%

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury

et al. 2016

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The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

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Section: Bradykininmentioning

confidence: 97%

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury

et al. 2016

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“…The deepest part of the lesion is limited to the Rexed's laminae VIII [58][59][60][61]. The model is quite reproducible and the extent of lesion varied only within a narrow range [8,58,59,[62][63][64].…”

Section: The New Rat Model Of Scimentioning

confidence: 99%

“…The details of structural and functional properties of the BSCB in normal and pathological conditions are not well known in all details [2][3][4][5]. Traumatic insults to the spinal cord disrupt the functional integrity of the BSCB and results into an increased transport of several substances from the vascular compartment to the spinal cord cellular microenvironment [1,[5][6][7][8][9][10][11]. Breakdown of the BSCB thus appears to play important roles in cell and tissue reaction as well as regeneration and repair processes [7,12].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Sharma¹

2005

CPD

158

218

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Blood-spinal cord barrier (BSCB) plays an important role in the regulation of the fluid microenvironment of the spinal cord. Trauma to the spinal cord impairs the BSCB permeability to proteins leading to vasogenic edema formation. Several endogenous neurochemical mediators and growth factors contribute to trauma induced BSCB disruption. Studies carried out in our laboratory suggest that those drugs and neurotrophic factors capable to attenuate the BSCB dysfunction following trauma are neuroprotective in nature. Whereas, agents that do not exert any influence on the BSCB disruption failed to reduce cell injury. These observations are in line with the idea that BSCB disruption plays an important role in the pathophysiology of spinal cord injuries. The probable mechanism(s) of trauma induced BSCB dysfunction and its contribution to cell injuries are discussed.

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“…Because it both catalyses destruction of a vasodilator (BK) and the formation of a vasoconstrictor (AT), ACE is an important target for drugs against hypertension. Accordingly, not only the decreased level of angiotensin II but also the elevated BK concentration in plasma is regarded to mediate ACE inhibitor effects because the higher risk of angio-oedema, which is a side effect of anti-hypertensive therapy with ACE inhibitors [10], can be fought with antagonists of the BK receptor type II (B2R) [34].…”

Section: Introductionmentioning

confidence: 99%

Bradykinin shifts endothelial fluid passage from para- to transcellular routes

Riethmüller

Jungmann

Wegener

et al. 2006

Pflugers Arch - Eur J Physiol

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The signalling peptide bradykinin (BK) is implicated in inflammation and angiogenesis. It promotes fluid transport from blood vessels to interstitial space, and thus facilitates oedema formation. To clarify whether paracellular or transcellular pathways mediate this effect, we investigated the BK-stimulated fluid transport across endothelial monolayers in vitro by comparison of electrical and fluorescence methods. Electrical cell impedance sensing monitored a biphasic response of cell layers to BK with high time resolution: a short decrease (18%, 1 min) was followed by a more sustained increase in paracellular resistance (30%, 10 min). The two phases can be assigned to second messengers of the BK-signalling pathway: Ca(2+) for the decrease and cyclic adenosine monophosphate for the rise of resistance, respectively. Despite tightening of the intercellular clefts, BK increased the fluid permeability by 39%, indicating transcellular fluid transport. Additionally, BK stimulated both in- and outwardly directed membrane trafficking as assessed by vesicular fluid uptake (by 49%) and secretion of von Willebrandt factor (by 85%). In conclusion, the combination of electrical and fluorescence data suggests that BK induces a shift from para- to transcellular fluid transport across endothelium.

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A Bradykinin BK2 Receptor Antagonist HOE-140 Attenuates Blood-Spinal Cord Barrier Permeability Following a Focal Trauma to the Rat Spinal Cord

Cited by 14 publications

References 17 publications

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury

Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Bradykinin shifts endothelial fluid passage from para- to transcellular routes

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