Neuropathological Findings In Chronic Relapsing Experimental Allergic Neuritis Induced In The Lewis Rat By Inoculation With Intradural Root Myelin And Treatment With Low Dose Cyclosporin A

Experimental allergic neuritis (EAN) was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. Rats treated with subcutaneous cyclosporin A (CsA) (4mg/kg on 3 days per week from the day of inoculation until day 29) developed a chronic relapsing course. Tissues from the spinal cord, nerve roots, dorsal root ganglia and sciatic nerve of CsA-treated rats sampled during relapses and remissions were studied during or after episodes of acute EAN. Both control and CsA-treated animals studied in the first episode of EAN had evidence of inflammation and primary demyelination of the nerve roots and dorsal root ganglia. In control and CsA-treated animals in the second episode there was severe inflammation and demyelination and remyelination in the spinal nerves and sciatic nerves and dorsal columns of the spinal cord, particularly in later stages of the disease. In later episodes there was less inflammation, but there was continuing demyelination and onion bulbs were present. In animals sampled after recovery from chronic relapsing EAN onion bulbs were present. Occasional small onion bulbs were also observed in control animals that were inoculated with higher doses of myelin. Plasma cells were present in the inflammatory lesions of later episodes. Mast cells were also observed at different stages of the disease. We conclude that the CsA form of chronic relapsing EAN has clinical and pathological similarities with the human disease, chronic inflammatory demyelinating polyradiculoneuropathy

Plant performance across latitude: the role of plasticity and local adaptation in a clonal aquatic plant

Geographic variation can lead to the evolution of different local varieties within a given species, therefore influencing its distribution and genetic structure. We investigated the contribution of plasticity and local adaptation to the performance of a common aquatic plant (Potamogeton pectinatus) in contrasting climates, using reciprocal transplants at three experimental sites across a latitudinal cline in Europe. Plants from 54 genets, originally collected from 14 populations situated within four climatic regions (subarctic, cold temperate, mild temperate, and mediterranean) were grown in three different localities within three of these regions (cold temperate, Norway; mild temperate, The Netherlands; mediterranean, Spain). Tuber production was highest for the mild-temperate genets, irrespective of locality where the genets were grown. Selection coefficients indicated that populations at the European center of the species distribution perform better than all other populations, at all sites. However, marginal populations showed changes in life-history traits, such as compressed life cycles in the north and true perenniality in the south, that may allow them to perform better locally, at the limits of their distribution range. Our results thus suggest that local adaptation may overlap spatially with center–periphery gradients in performance caused by genetic factors (such as genetic drift and inbreeding in range-marginal populations Key words:climate; clonal reproduction; distribution; latitude; [KEYWORDS: climate; clonal reproduction; distribution; latitude; local adaptation; plasticity; Potamogeton pectinatus; reciprocal transplant; shoot morphology; survival; vegetative growth]

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy.Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later.Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007).Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy