Figure 6.

Locus coeruleus neuronal stress is present in multiple sclerosis. (A) Noradrenaline (NA) levels were measured in 10 areas located near the locus coeruleus as described in ‘Methods’ section, in samples from five patients with multiple sclerosis (MS) and seven controls (Ctrl), and values from the 10 areas averaged. Data are means ± SEM of pg noradrenaline/mg wet weight; *P < 0.05 versus controls. Representative images of tyrosine hydroxylase staining from control (B) and patient with multiple sclerosis (C) encompassing most of the locus coeruleus. Quantitative image analysis carried out on nine serial sections from eight multiple sclerosis and eight control samples did not show any significant difference in the total number of tyrosine hydroxylase positive stained neurons per field of view (D); however, the average cell size was significantly increased in patients with multiple sclerosis (E). The distribution of tyrosine hydroxylase positive cell sizes (F) calculated from 3408 cells in the patients with multiple sclerosis (filled circles) and 3660 cells from the controls (open circles) shows fewer cells of size range 700–900 µm² in patients with multiple sclerosis compared with controls [F(11, 1) = 2.131, P = 0.021], with a significantly greater percentage of cells having areas >1500 µm² in the patients with multiple sclerosis (F, inset). Data are means ± SEM, *P < 0.01 versus controls (Bonferroni’s post hoc). Each cell size bin includes cells with areas that size ± 100 µm². Scale bars are 200 µm.