Evaluation of the Parawixin-2 neuroprotective activity, isolated from the spider Parawixia bistriata, in an acute ischemic stroke model induced by Endothelin-1 in Wistar rats

Abstract

Ischemic stroke (IS) is the most common neurodegenerative disorder and the main cause of motor incapacity in adults. When blood flow is occluded in Central Nervous System, it induces imbalance of the major excitatory and inhibitory neurotransmitters, L-Glutamate (L-Glu) and ³-Amino-butyric acid (GABA). The most common IS involves occlusion of the middle cerebral artery (MCA) directly reaching cortical areas. This type of injury leads to cognitive, motor and somatosensory deficits. Therefore, mechanisms that are capable to reduce cease or even counteract the neural injury. Blocking GABA reuptake into the synaptic cleft may be a promising tool by establishing the balance between GABA and L-Glu, thus generating a neuroprotective effect. In the search for neuroprotective compounds, Parawixin-2 (Pwx-2) stands out. Its notable effect of GABA transporter inhibitor has already showed neuroprotective activity in retinal ischemic model. The main objective of this study is to evaluate the neuroprotective potential of Pwx-2 in Wistar rats submitted to the Et-1 induced focal ischemia model. The experimental model of MCA occlusion uses the vasoconstrictor peptide Endothelin-1 (Et-1) in the vicinity of ACM. This model has translational potential, as it involves circumscribed focal lesion and, in addition, a refined surgical procedure used generates low mortality. The infarct area will be evaluated through the TTC histochemistry technique (metabolic activity staining). To evaluate neurodegeneration, the Fluoro Jade-C technique will be used in somatosensory cortex, primary motor and striatum. The motor and functional evaluation will consist of open field, grid grip, paw asymmetry and tail suspension tests.