Breakdown of the blood-brain barrier and neuropathological changes induced by Phoneutria nigriventer spider venom

dc.creatorLe Sueur, LD
dc.creatorKalapothakis, E
dc.creatorda Cruz-Hofling, MA
dc.date2003
dc.dateFEB
dc.date2014-11-15T03:14:43Z
dc.date2015-11-26T16:30:40Z
dc.date2014-11-15T03:14:43Z
dc.date2015-11-26T16:30:40Z
dc.date.accessioned2018-03-28T23:11:43Z
dc.date.available2018-03-28T23:11:43Z
dc.identifierActa Neuropathologica. Springer, v. 105, n. 2, n. 125, n. 134, 2003.
dc.identifier0001-6322
dc.identifier1432-0533
dc.identifierWOS:000180855300007
dc.identifier10.1007/s00401-002-0623-8
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/63252
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/63252
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/63252
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1270019
dc.descriptionThe blood-brain barrier (BBB) is responsible for selective flux of substances between blood and brain. The selective permeability of the BBB is crucial for the maintenance of the brain microenvironment homeostasis, and alterations in the barrier may be involved in many pathophysiological processes. Phoneutria nigriventer armed spider venom produces excitatory signals and symptoms in humans, and its recognized neurotoxic action suggests a potential ability to alter BBB permeability. The aim of the present study was to investigate the capacity of P. nigriventer venom (PNV) in promoting BBB breakdown in adult rats. After intravenous injection of 850 mug/kg of the whole venom, BBB lesions were evaluated after 18 h to 9 days by ultrastructural methods using the extracellular tracer lanthanum nitrate. Clinical signs and symptoms of rats showed acute neurotoxicity, with some of the animals presenting convulsions, but which were clinically resolved by 12 h post-envenoming. The results showed that PNV is able to increase BBB permeability, particularly in the hippocampus. Changes were first detected in arterioles and post-capillary venules 18 h to 5 days after venom inoculation. The increased permeation of the extracellular tracer peaked on day 1, representing about 42% of the examined vessels (P<0.01). This appeared to occur by both transendothelial and intercellular routes, i.e., by pinocytic transport and through interendothelial junctions. Concomitantly, the surrounding tissue showed vasogenic edema and swollen astrocytic processes, without inflammatory infiltrates. The peak of the edema occurrence was observed on day 3, in about 60% of the vessels (P<0.001). Enhanced capillary permeability was observed on day 9, and affected 36% of all capillaries (P<0.05). The affected capillaries were characterized by increased number of pinocytotic vesicles, which, in addition, were filled with the extracellular tracer, but without visible transport through the interendothelial pathway. This study demonstrates that systemic PNV inoculation induces BBB breakdown through trans- and paracellular routes. It is concluded that BBB breakdown is an event not associated with the acute neurotoxicity exhibited by the rats.
dc.description105
dc.description2
dc.description125
dc.description134
dc.languageen
dc.publisherSpringer
dc.publisherNew York
dc.publisherEUA
dc.relationActa Neuropathologica
dc.relationActa Neuropathol.
dc.rightsfechado
dc.rightshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.sourceWeb of Science
dc.subjectblood-brain barrier
dc.subjectbrain vasogenic edema
dc.subjectextracellular tracer
dc.subjectpermeability
dc.subjectPhoneutria nigriventer venom
dc.subjectIncreased Vascular-permeability
dc.subjectAmino-acid-sequence
dc.subjectHorseradish-peroxidase
dc.subjectRabbit Skin
dc.subjectNeurotoxic Peptides
dc.subjectSmooth-muscle
dc.subjectKinin System
dc.subjectRat
dc.subjectPolypeptide
dc.subjectToxin
dc.titleBreakdown of the blood-brain barrier and neuropathological changes induced by Phoneutria nigriventer spider venom
dc.typeArtículos de revistas


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