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

Toxicol Sci. 2014 Jan;137(1):147-57. doi: 10.1093/toxsci/kft231. Epub 2013 Oct 8.


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 (CNS) 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 3 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 magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min 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 Fluor 568 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.

Keywords: cerebral blood flow.; encephalic perfusion; glucose utilization; scorpion envenoming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Blood Flow Velocity
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain Stem / blood supply
  • Brain Stem / drug effects*
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Capillary Permeability / drug effects
  • Cerebrovascular Circulation / drug effects
  • Deoxyglucose / metabolism
  • Disease Models, Animal
  • Hemodynamics / drug effects
  • Laser-Doppler Flowmetry
  • Magnetic Resonance Imaging
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Rats
  • Rats, Wistar
  • Scorpion Stings / pathology*
  • Scorpion Venoms / toxicity*
  • Scorpions*
  • Severity of Illness Index
  • Time Factors


  • Scorpion Venoms
  • Deoxyglucose