Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation

Patrícia Alves Maia Guidine; Diana Cash; Luciana Estefani Drumond; Gustavo Henrique de Souza E Rezende; André Ricardo Massensini; Steve Charles Reese Williams; Tasso Moraes-Santos; Márcio Flávio Dutra Moraes; Michel  Bernanos Soares Mesquita

doi:10.1093/toxsci/kft231

Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation

Patrícia Alves Maia Guidine, Diana Cash, Luciana Estefani Drumond, Gustavo Henrique de Souza E Rezende, André Ricardo Massensini, Steve Charles Reese Williams, Tasso Moraes-Santos, Márcio Flávio Dutra Moraes, Michel Bernanos Soares Mesquita

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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.

Original language	English
Journal	Toxicological sciences : an official journal of the Society of Toxicology
DOIs	https://doi.org/10.1093/toxsci/kft231
Publication status	E-pub ahead of print - 2013

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10.1093/toxsci/kft231

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Maia Guidine, P. A., Cash, D., Drumond, L. E., Rezende, G. H. D. S. E., Massensini, A. R., Williams, S. C. R., Moraes-Santos, T., Dutra Moraes, M. F., & Bernanos Soares Mesquita, M. (2013). Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation. Toxicological sciences : an official journal of the Society of Toxicology. Advance online publication. https://doi.org/10.1093/toxsci/kft231

@article{bb6540648e8a4cae9bffefff9eacdee4,

title = "Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation",

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.",

author = "{Maia Guidine}, {Patr{\'i}cia Alves} and Diana Cash and Drumond, {Luciana Estefani} and Rezende, {Gustavo Henrique de Souza E} and Massensini, {Andr{\'e} Ricardo} and Williams, {Steve Charles Reese} and Tasso Moraes-Santos and {Dutra Moraes}, {M{\'a}rcio Fl{\'a}vio} and {Bernanos Soares Mesquita}, Michel",

year = "2013",

doi = "10.1093/toxsci/kft231",

language = "English",

journal = "Toxicological sciences : an official journal of the Society of Toxicology",

issn = "1096-6080",

publisher = "Oxford University Press",

}

Maia Guidine, PA, Cash, D, Drumond, LE, Rezende, GHDSE, Massensini, AR, Williams, SCR, Moraes-Santos, T, Dutra Moraes, MF & Bernanos Soares Mesquita, M 2013, 'Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation', Toxicological sciences : an official journal of the Society of Toxicology. https://doi.org/10.1093/toxsci/kft231

TY - JOUR

T1 - Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation

AU - Maia Guidine, Patrícia Alves

AU - Cash, Diana

AU - Drumond, Luciana Estefani

AU - Rezende, Gustavo Henrique de Souza E

AU - Massensini, André Ricardo

AU - Williams, Steve Charles Reese

AU - Moraes-Santos, Tasso

AU - Dutra Moraes, Márcio Flávio

AU - Bernanos Soares Mesquita, Michel

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1093/toxsci/kft231

DO - 10.1093/toxsci/kft231

M3 - Article

C2 - 24105889

SN - 1096-6080

JO - Toxicological sciences : an official journal of the Society of Toxicology

JF - Toxicological sciences : an official journal of the Society of Toxicology

ER -

Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation

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