hASM levels in (A) rat brain, (B) spinal cord and (C) serum following a 6 h ICV infusion of hASM at different doses (0.1, 1.0 and 10 mg/kg) or aCSF.

<p>Significant (p<.01) levels of hASM were detected in all regions of the brain (i.e., cortex, preoptic region, striatum, hippocampus, thalamus, hypothalamus, midbrain, cerebellum and brainstem) in rats infused with 1 and 10 mg/kg of the enzyme. Rats infused with the 0.1 mg/kg dose displayed significant hASM levels in the cortex, preoptic region, striatum and hippocampus. No significant differences in hASM levels between regions were observed regardless of the dose tested. In each region of the spinal cord, significant (p<.01) levels of hASM were also detected in rats infused at either 1 or 10 mg/kg vs. rats infused with aCSF (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016313#pone-0016313-g002" target="_blank">Figure 2b</a>). Detected hASM levels in rats infused with 0.1 mg/kg were not significantly above background. Significant (p<.01) levels of hASM were detected in serum for all hASM infused rats regardless of the dose of enzyme used.</p

Percentage of the total administered dose of hASM detected in the (A) brain, (B) spinal cord and (C) serum of rats following 6 h ICV infusion.

<p>Animals were infused with 0.1, 1.0 or 10 mg/kg of hASM or aCSF. For both the brain and spinal cord, less than 0.2% of the total dose could be detected in each region. Cumulatively, the level of hASM detected in the brain and spinal cord was less than 1% of the total dose administered. No significant differences were observed between regions or different dose groups. Significant (p<.01) levels of hASM were detected in serum for each dose.</p

(A) Distribution of hASM in the rat CNS following a 6 h ICV infusion of hASM or aCSF (S1 = most rostral brain section and S5 = most caudal brain section, S6 = cervical spinal cord).

<p>Positive hASM staining was observed throughout the brain and spinal cord of rats administered with the enzyme. Staining intensity was maximal in regions proximal to ventricular compartments and the sub-arachnoid space. (B) Higher magnification (4× for brain; 20× for spinal cord) of hASM staining in regions between ventricular compartments and the tissue proximal to the sub-arachnoid space (area enclosed within the white box of sections S2 and S6). Shown are images from the brain and cervical spinal cord.</p