SFE2004 Poster Presentations Diabetes, metabolism and cardiovascular (18 abstracts)
Loss of normal blood-brain barrier (BBB) function is an integral feature of the neuroinflammatory process in the human demyelinating disease multiple sclerosis (MS). Our previous studies using EAE as the experimental model of MS have demonstrated that restoration of BBB function is associated with an improved clinical status. The vasoactive peptide ADM works in an autocrine manner on endothelial cells of the vasculature and is produced at particularly high levels within the neurovasculature. In vitro work has shown that the peptide can regulate BBB characteristics including transendothelial electrical resistance, permeability and p-glycoprotein pump activation. Therefore, ADM-mediated control of BBB function may be a viable therapeutic target for modulating the course of EAE and ultimately MS. The aim of this study was to assess the involvement of ADM in the onset and development of EAE.
ADM was extracted from dissected CNS tissues and plasma prepared from sacrificed normal and EAE-sensitised rats at days 9 and 15 post-inoculation (PI). The peptide was measured using a commercial radioimmunoassay. Results from our initial studies showed no change in ADM concentration in the cerebellum, at either time point, compared to normal tissue levels. However, an elevation in the peptide was observed, at day 15 PI, in EAE cervical spinal cord tissues (p<0.01) corresponding with a time-matched increase in circulating ADM levels (p<0.05). Moreover, the tissue-specific elevation in ADM appears to follow the profile for improvement of BBB permeability in the two tissue areas analysed at the selected time points. In conclusion, endogenous ADM may have a role in the restoration of normal BBB function in conditions such as EAE and MS and thus provide a therapeutic opportunity for disease control.