The correlation between severity of paraparesis and reduced density of resident antigen-presenting cells implicates an unknown role for the spinal perivascular macrophages in experimental autoimmune encephalomyelitis in rats.

To study alterations in the morphology of spinal perivascular macrophages (SPM) during experimental allergic encephalomyelitis (EAE), we labelled SPM by intracerebroventricular (i.c.v.) injection of horseradish peroxidase (HRP). As earlier electron microscopical analysis had shown severely damaged SPM, we suspected that each inflammatory process is accompanied by the death of SPM. To prove this hypothesis, we compared the numerical density of resident SPM (i.c.v. labelled in red by Fluoro-Ruby) with that of monocytes/macrophages recruited to the perivascular space (i.c.v. labelled in green by Fluoro-Emerald). At the peak of paraparesis, the density of resident SPM was reduced by 33%. Since this reduction contrasted sharply with earlier data indicating a massive increase in the density of SPM during EAE, we checked our findings after general or selective suppression of the immune response to myelin autoantigens with the drugs dexamethasone and copaxone, respectively. Dexamethasone treatment commenced after evident paraparesis accelerated recovery, but did not influence SPM density. Immunisation with copaxone completely prevented the occurrence of EAE (monitored by video-based motion analysis of tail motility); the subsequent histological analysis revealed no reduction in SPM density. Based on this inverse correlation between the severity of EAE and the density of resident macrophages, we conclude that SPM plays an important role in the pathogenesis of EAE.

An example of neural plasticity evoked by putative behavioral demand and early use of vibrissal hairs after facial nerve transection.

Abnormally associated movements inevitably occur after surgical repair of the facial nerve. The reason for this postparalytic syndrome is poor navigation of regrowing axons. Despite the valuable functional advantage provided by the easily detected movement of vibrissae in rats, the major investigative tools for establishing the degree of misdirected reinnervation are still electrophysiologic recordings and retrograde tracing. In the present study we complemented data from pre- and postoperative retrograde labeling (FluoroGold, Fast Blue, DiI) of facial motoneurons with an evaluation of whisker movements. Using a video-based motion analysis system, we compared the recovery of vibrissae motor performance in visually normal and blind rats of the Sprague-Dawley strain. The analysis of whisker movement after facial nerve surgery revealed a striking discrepancy between morphologic and functional estimates. Whereas retrograde labeling displayed poor accuracy of target reinnervation and supernumerary axonal branching in both groups, the video-based motion analysis showed a perfect recovery of vibrissae movements in the blind rats. Attributing the complete recovery of whisker movement in the blind rats to an extraordinary plasticity of the facial motoneurons induced by putative behavioral demand and forced overuse, we conclude that the video-based analysis of whisker movement is a valuable tool for studying the progress in functional recovery.

Transplantation of olfactory mucosa minimizes axonal branching and promotes the recovery of vibrissae motor performance after facial nerve repair in rats.

The occurrence of abnormally associated movements is inevitable after facial nerve transection. The reason for this post-paralytic syndrome is poor guidance of regrowing axons, whereby a given muscle group is reinnervated by misrouted axonal branches. Olfactory ensheathing glia have been shown to reduce axonal sprouting and stimulate axonal regeneration after transplantation into the spinal cord. In the present study, we asked whether transplantation of olfactory mucosa (OM) would also reduce sprouting of a damaged peripheral pure motor nerve. The adult facial nerve was transected, and the effect of the OM placed at the lesion site was analyzed with regard to the accuracy of target reinnervation, axonal sprouting of motoneurons, and vibrissal motor performance. Accuracy of target reinnervation and axonal sprouting were studied using preoperative/postoperative labeling and triple retrograde labeling of facial motoneurons, respectively. The vibrissal motor performance was monitored using a video-based motion analysis. We show here that implantation of OM, compared with simple facial-facial anastomosis, (1) improved the protraction, amplitude, angular velocity, and acceleration of vibrissal movements up to 80% of the control values, (2) reduced the percentage of branching motoneurons from 76 to 39%, and (3) improved the accuracy of reinnervation from 22 to 49%. Moreover, we present evidence, that transplanted OM but not buccal mucous membrane induced a sustained upregulation of trophic factors at the lesion site. It is concluded that transplantation of OM to the transected facial nerve significantly improves nerve regeneration.