Citation

Maia Guidine PA, Cash D, Drumond LE, Rezende GH, Massensini AR, Rees Williams SC, Moraes-Santos T, Dutra Moraes MF, Soares Mesquita MB. Toxicol. Sci. 2014; 137(1): 147-157.

Affiliation

Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, 31270 901 Belo Horizonte, Minas Gerais, Brazil.

Copyright

(Copyright © 2014, Oxford University Press)

DOI

10.1093/toxsci/kft231

PMID

24105889

Abstract

Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in three hypotheses: 1) The shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas; 2) The neurons within these areas have high affinity to the toxins and 3) The neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological MRI paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction one minute after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by Laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa-568 labeled TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.

Language: en