2C and F). However, envenomed neonate rats showed a 83.1% increase in the water channel AQP4 expression at 2 h (**p ≤ 0.01), a 58.8% increase at 5 h (**p ≤ 0.01) and a 23.5% non-significant increase at 24 h indicating that after an immediate rise the expression of AQP4 declined with time toward baseline. On the PS-341 clinical trial other hand, relative to controls PNV-administered adult rats showed a 59.8% increase of AQP4 expression at 2 h (*p ≤ 0.05), 39.5% (not significant) at 5 h and 91.8% at 24 h (*p ≤ 0.05) indicating a prolonged

effect of PNV on the expression of the protein ( Fig. 3C). GFAP expression showed no significant change in response GSK-3 activity to PNV in P14 animals; however, in adult rats it induced a 71.2% increase at 2 h (***p ≤ 0.001) and 33.5% at 5 h (*p ≤ 0.05) and was close to baseline at 24 h ( Fig. 3F). The two-way analysis of variance showed that with regard to the granular layer the variable time after injection interfered in the expression of AQP4 (***p ≤ 0.001) and GFAP (***p ≤ 0.05) in neonates and AQP4 and GFAP (***p ≤ 0.001) in adults. Also, there was interaction between the

age variable and PNV treatment in the expression of AQP4 at 2 h (***p ≤ 0.001), 5 h (**p ≤ 0.01) and 24 h (**p ≤ 0.01) and GFAP at all time intervals (**p ≤ 0.01; *p ≤ 0.05; *p ≤ 0.05, respectively). The smallest value of AQP4 expression in Bergmann glia cells for neonate was 15.73 ± 2.61 and for adult rats was 16.39 ± 1.62, whereas the highest value was 23.95 ± 2.16 for neonates and 22.96 ± 3.45 for adults (Fig. 4C). The expression of GFAP was slightly higher in P14 animals than in

the adults ranging from 23.53 ± 2.19 to 29.31 ± 2.16 in P14 and 20.23 ± 1.51 to 23.83 ± 2.46 in adults (Fig. 4F). The effect of PNV on AQP4 expression was significant only after 24 h when a 52% upregulation was found for Bergman glia of 8-week-old rats (*p ≤ 0.05) ( Fig. 4C). In contrast, in 14-day-old rats a 44.2% Fossariinae increase occurred earlier at 2 h (*p ≤ 0.05), but its level did not differ from the control at 5 h and then increased 101.6% at 24 h (*p ≤ 0.01) relative to the baseline ( Fig. 4C). GFAP expression showed no alteration in P14, whereas it rose significantly by 66.34% at 2 h (***p ≤ 0.001), 51.11% at 5 h (**p ≤ 0.01) and 58.59 at 24 h (**p ≤ 0.01) above baseline counterparts ( Fig. 4F). The two-way analysis of variance showed that the time elapsed between envenomation and animal euthanasia interfered with the expression of AQP4 in P14 (***p ≤ 0.001) and GFAP in adults (*p ≤ 0.05). Also, the age variable interacted with PNV treatment relative to AQP4 expression at 24 h (***p ≤ 0.001) and GFAP expression at 2 h (**p ≤ 0.01). Fig.