TY  - JOUR
PY  - 2014//
TI  - Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation
JO  - Toxicological sciences
A1  - Maia Guidine, Patrícia Alves
A1  - Cash, Diana
A1  - Drumond, Luciana Estefani
A1  - Rezende, Gustavo Henrique de Souza E.
A1  - Massensini, André Ricardo
A1  - Rees Williams, Steve Charles
A1  - Moraes-Santos, Tasso
A1  - Dutra Moraes, Márcio Flávio
A1  - Soares Mesquita, Michel Bernanos
SP  - 147
EP  - 157
VL  - 137
IS  - 1
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.<p />  <p>Language: en</p>
LA  - en
SN  - 1096-6080
UR  - http://dx.doi.org/10.1093/toxsci/kft231
ID  - ref1
ER  -