Because of that, when comparing envenomed neonates and envenomed adult rats there was a tendency in decreasing the

water channel protein expression only at 5 h. In contrast, PNV induced a 116.13% increase (*p ≤ 0.05) in GFAP expression in astrocytes located in the Purkinje layer ( Fig. 5C). The two-way analysis of variance showed that the age variable of the animals interacts with the treatment affecting the expression of GFAP after 24 h of envenomation. One consequence of P. nigriventer experimental envenomation in rats is perivascular edema, swollen astrocyte endfeet and extravasation of extracellular tracer ( Le Sueur et al., 2003; Rapôso et al., 2007). The conspicuous excytotoxic signs exhibited by animals and indicative of neurotoxicity course with SB431542 mouse enhanced vesicular transcellular transport ( Le Sueur et al., 2004)

and displacement and phosphorylation of tight and adhesion junctional proteins learn more engaged in the prevention of the paracellular transport ( Rapôso et al., 2012). Other consequences of PNV effects in rats include astrogliosis, upregulation of GFAP, S100, and nNOS proteins and TNF-α and IFN-γ pro-inflammatory cytokines in hippocampus and cerebellum implying reactive involvement of these glial cells in the envenomation effects and evidence of BBB violation ( Cruz-Höfling et al., 2009). In addition, PNV causes in vivo upregulation of the Poly-glycoprotein (P-gp), which though transient, is followed by upregulation ( Rapôso et al., 2012). In primary culture of cortical-derived astrocytes, the venom was shown to inhibit the activity of the P-gp, a protein belonging to the multidrug resistance (MDR) efflux transporter protein family (ABCB1) which in the brain works to protect tissue against potential risky compounds ( Bodo et al., 2003; Fromm, 2003). Herein, the P. nigriventer venom (PNV) induced increased expression of AQP4 in astrocytes of the cerebellum evidencing a novel role of the water channel protein

to counteract venom effects. Although generally described as present in the astroglial foot processes facing fluid compartments, including the BBB, we found strong AQP4 immunoreactivity in the interstices among the neurons of the granular and Purkinje layers in addition Edoxaban to its expression around microvessels. In the ML, the AQP4 expression appeared in tiny Bergman glia ramifications across the layer width. There was no AQP4 expression by neurons of the cerebellum cortex corroborating the view that water homeostasis, and probably K+ siphoning are events selectively performed by astrocytes ( Nico et al., 2002; Verkman et al., 2006). We found that the physiological AQP4 expression showed a tendency to be higher in P14 animals than in adults injected with saline. Our results contrast with a previous study reporting that AQP4 expression in P14 post-natal rats is 25% of the adult level (Wen et al., 1999).