Number Of Myelinated Fibers Research Articles

TrkB and TrkC agonist antibodies improve function, electrophysiologic and pathologic features in TremblerJ mice

Neurotrophic factors have been considered as potential therapeutics for peripheral neuropathies. Previously, we showed that neurotrophin-3 (NT-3) promotes nerve regeneration in TremblerJ (TrJ) mice and in sural nerves from patients with Charcot–Marie–Tooth 1A (CMT1A). The relatively short plasma half-life of NT-3 and other neurotrophins, however, pose a practical difficulty in their clinical application. Therapeutic agonist antibodies (AAb) targeting the neurotrophic receptors may circumvent this obstacle due to their high specificity and long half-life. Using morphological, electrophysiological studies and functional motor testing, we assessed the efficacy of monoclonal TrkC AAb and TrkB AAb in the TrJ mice. Treatments of these AAbs individually or in combination over 20weeks increased compound muscle action potential (CMAP) amplitude, which correlated with improved grip strength, as compared to the PBS control group. Improvements in CMAP amplitude were most prominent with TrkC AAb treatment. In all treatment groups, distal to the crush site of the sciatic nerves exhibited a significantly greater number of myelinated fibers (MFs) indicating improved regenerative response to injury. In the contralateral intact sciatic nerves, the number of MFs as well as the myelin thickness was also increased significantly by the AAb treatments, suggesting that the hypomyelination/amyelination state of the peripheral nerves in TrJ improved. Therapeutic response to AAb combination was often, albeit not always, the most prominent, indicating a non-redundant effect of TrkB and TrkC AAbs. An early functional recovery and the correlative morphological changes of enhanced regeneration were seen with TrkC AAb treatment. These results provide evidence for potential therapeutic use of monoclonal agonist antibodies for neurotrophin receptors in CMT1A and other neuropathies.

The nerve regeneration after end-to-side nerve anastomosis of distal stump of autonomic nerve to somatic nerve in rats

Objective To observe the nerve regeneration after end-to-side anastomosis of distal stump of autonomic nerve to somatic nerve in rats. Methods Twenty-four Sprague-Dawley rats were divided into two groups: experimental group (n = 12) and control group (n = 12). In experimental group, rats had the left lumbar 6 ventral root (L6VR) transected in dura and the distal stump was sutured to the lateral face of left lumbar 4 ventral root (L4VR). In control group, rats had not been done any surgery. After 6 months, in experimental group, the nerves were intercepted 10 mm in length, from the proximal and distal end-to-side nerve anastomosis, regarded as donor nerve (L4VR) and recipient nerve (L%VR), and 10 mm from the pelvic parasympathetic nerve (PPN) and pudendal nerve (PN) from L6VR was intercepted, respectively. In control group, the corresponding nerves were harvested. The cross-sectional nerve slices were stained with toluidine blue through the use of histochemical technique, and the number of myelinated nerve fibers was counted. By comparing L6VR with L4VR the nerve passing rate was calculated, and the number of the nerve fibers of L6VR, PPN and PN between experimental group and control group was compared. Results The new myelinated nerve fibers were observed in the cross-sectional slices of the experimental rats. The number of the nerve fibers located in the L4VR, L6VR, PPN and PN was 1602. 2 ± 75.7,1037.9 ± 123.6, 817. 0 ±52. 2 and 510. 4 ± 29. 1, respectively. The nerve passing rate of the distal and the proximal ends from the anastomosis was 64. 8%, the ratio of the number of nerve fibers in L6VR, PPN and PN was 70.2%, 68.9% and 62.2%, respectively, between the experimental group and control group. Conclusion The somatic nerve can grow into and replace the autonomic nerve after the reflex pathway established by end-to-side anastomosis of autonomic nerve and somatic nerve in rats. Key words: End-to-side coaptation; Nerve regeneration; Somatic nerve; Autonomic nerve

Myelination in the human hippocampal formation from midgestation to adulthood

Myelination, one of the last steps of neuronal development, was examined in the human fetal and postnatal hippocampal formation using immunohistochemistry to detect a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelin basic protein-immunoreactive oligodendroglial cells were first seen at the 20th gestational week in the fimbria fornicis and in the alveus. Between the 21st and 35th weeks, myelinated axons also appeared in the fimbria fornicis. At the age of 39 gestational weeks, short and thin myelinated fibers were present in the fimbria, in the alveus, and less so in the stratum oriens of the hippocampus, while the first oligodendroglial cells appeared in the stratum lacunosum-moleculare and in the hilus. By the 2nd postnatal week myelinated fibers appeared in the stratum lacunosum-moleculare of Ammon's horn. At the 3rd month, myelination was strong in the alveus, moderate in the strata oriens, lacunosum-moleculare and radiatum of Ammon's horn, while only a small number of myelinated fibers were detected in the hilus. By the 5th month, the first oligodendroglial cells were detected in the molecular layer of the dentate gyrus. Myelination continued in the following years, particularly in the dentate gyrus, where even at the age of 11 years the density of myelinated fibers did not reach the adult level. It appears that the first myelinated axons belong to the long-projecting large hippocampal pyramidal cells and/or to their subcortical and cortical afferents. The sequence of myelination follows the known developmental pattern of hippocampal afferent and efferent pathways, and the prolonged myelination might be a factor in the prolonged functional maturation of hippocampal circuitry.

The Action of Topical Basic Fibroblast Growth Factor in Facial Nerve Regeneration

To analyze the influence of the topical use of basic fibroblast growth factor (bFGF) in the regeneration of the facial nerve in rats. Experimental study. Twenty-eight Wistar adult male rats underwent complete section of the facial nerve trunk, followed by end-to-end anastomosis with epineural sutures. An osmotic minipump equipped with a delivery catheter was implanted subcutaneously near the neural anastomosis. During the subsequent 14 days, 14 animals received a solution containing 25 microg/ml of bFGF, 250 UI/ml of sodium heparin, and 1,000 microg/ml of human albumin diluted in Ringer lactate, and 14 animals received a control solution of the same components without bFGF. To evaluate facial nerve regeneration, the number of myelinated fibers evident on histologic sections was counted on the 14th (7 experimental and 8 control animals) and the 28th days (7 experimental and 6 control animals) after surgery, and the facial movements of vibrissae and the blink reflex were evaluated on alternate days until the 28th day. On histologic evaluation, the number of myelinated fibers was similar between groups on the 14th day and greater in the group that received bFGF on the 28th day. Behavioral evaluation showed that the animals of the bFGF group presented better functional results between the 6th and 16th days for the blink test and the 14th to the 16th days for vibrissae movements. This study showed that the regeneration of the facial nerve occurred earlier and resulted in significantly more myelinated nerve fibers in the animals that received topical bFGF.

Phrenic nerve morphometry in male and female spontaneously hypertensive rats

Histological examination of the diaphragm showed gender differences in fiber composition but gender differences on phrenic nerve morphometry were not thoroughly addressed. Ventilatory differences were described between male and female rats, as well as among different rat strains. However, the morphology of the phrenic nerve was not investigated in spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) rats. After arterial pressure and heart rate recordings, phrenic nerves of 20 week‐old male and female SHR and WKY were prepared for epoxy resin embedding and light microscopy. Morphometry was performed with the aid of computer software. Our results showed for male and female SHR remarkable longitudinal asymmetry on both sides and an asymmetry between sides on distal segments, which were not present on WKY nerves. Phrenic nerves were generally larger in males compared to females on both strains but larger on WKY compared to SHR for both genders. Myelinated fiber number and density were significantly larger on females of both groups and remarkably larger on WKY compared to SHR in both genders. Strain and gender differences on phrenic nerve myelinated fiber number is described for the first time in this experimental model of hypertension, pointing to the need for thorough functional studies of this nerve on male and female SHR.Grant Funding Source: FAPESP

Morphometric analysis of the human superficial radial nerve

The superficial radial nerve (SRN) is one of the cutaneous nerves biopsied for diagnosis of peripheral neuropathy. Morphometric analysis is employed to provide more quantitative data regarding the histomorphology of nerve biopsy. To detect early structural changes, morphometric data from normal nerves are necessary for diagnostic criteria. Unlike the sural nerve, morphometric data on the normal SRN have not been reported. Therefore, a morphometric analysis of the normal human SRN was done in this study. The nerves were harvested bilaterally from 21 fresh human bodies, yielding 34 nerves after excluding damaged ones. Transverse semi-thin sections were analyzed for the number of fascicles, myelinated fiber and axon diameters, myelin sheath thickness, g ratio, density and total number of myelinated fibers using the three-window sampling method. We found that 2-16 fascicles were present. Mean fiber and axon diameters were 6.32 +/- 0.09 (SEM) and 3.44 +/- 0.06 microm, respectively. Average myelin thickness was 1.44 +/- 0.03 microm. Average g ratio was 0.56 +/- 0.01. Mean density of fibers was 8,872.9 +/- 167.4/mm(2). The number of fibers varied from 1,390 to 10,941, with an average of 6,495 +/- 474. These parameters were independent of age. Asymmetry in the number of fibers was also noted in four cases. The data obtained in this study can be applied to histomorphometric evaluations of SRN biopsies, although the possibility of asymmetry should be considered.

Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa)

The aim of our project was to study the effect of streptozotocin (STZ)-induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products), and its ligands-S100B and Carboxymethyl Lysine (CML)-advanced glycation endproduct (AGE) in the laboratory pig. Six months after STZ-injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products-methyl-glyoxal (MG) were performed. The results of our study revealed that STZ-injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT) and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.

Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth

It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons’ reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental lumbar spinal cords. Taken together our results show that (1) rat motoneurons survived after 35-day antiorthostatic hind limb suspension and the changes in neurons had a mostly functional character, and (2) the increased immunoexpression of Hsp25 can be considered as the anti-apoptotic factor.

Aquatic Environment and Differentiation of Vibrissae: Comparison of Sinus Hair Systems of Ringed Seal, Otter and Pole Cat

This study investigated the structure and innervation of the vibrissal systems of the pole cat (Mustela putorius), European otter (Lutra lutra) and ringed seal (Phoca hispida) in order to find adaptations to aquatic environment. The number of myelinated nerve fibers of deep vibrissal nerve (DVN) of the entire vibrissal system was considerably greater in the ringed seal (10×, aquatic mammal) and in the otter (4×, semi-aquatic mustelid) compared to the pole cat which is a terrestrial mustelid. Similarly, the number of neural end organs in the vibrissae of ringed seals was about ten times more numerous than in pole cats. The number of the vibrissae in the heads of otters was almost two times more than in pole cats, and all vibrissa groups had similar structures and innervation. The asymmetrically developed carpal vibrissae of otters were, however, more poorly innervated than the vibrissae of the head and had only smooth musculature. In the ringed seal the orientation of lanceolate end organs differed in different vibrissae, indicating the specialization of these vibrissae for different kinds of sensory functions. Ringed seal vibrissae contain structures which obviously are developed as adaptations to an aquatic environment. These include the modified mitochondria of Merkel cells, with Merkel cell-neurite complexes very often associated ciliated cells, liquid filled vesicles or intercellular spaces below the basal cell layer of the outer root sheath at the ring sinus level, a long upper cavernous sinus and a flattened beaded structure of the vibrissa hairs. As the vibrissae of aquatic mammals have analogous functions to the lateral line organ of fishes, we suggest using the term ‘vibrissal sense’ for the vibrissa system of aquatic mammals.

Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury

We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 µg, 10 ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing.

Nerve Transfer for Wrist Extension Using Nerve to Flexor Digitorum Superficialis in Cervical 5, 6, and 7 Root Avulsions: Anatomic Study and Report of Two Cases

To evaluate the feasibility of restoring wrist extension in patients with complete cervical root 5 (C5), 6, and 7 avulsion injuries by transferring the most proximal branch of the median nerve that innervates flexor digitorum superficialis (FDS) muscle (proximal FDS branch) to the branch of the radial nerve that innervates extensor carpi radialis brevis (ECRB) muscle (ECRB branch) in an anatomic study and 2 case reports. The study was performed on 10 fresh cadavers. The nerve branches of the median nerve and the radial nerve were measured for length, diameter, and sites of origin of their nerve branches. The nerve branches of the median nerve, the posterior interosseous nerve, and the ECRB branch of the radial nerve were processed for histomorphometric evaluation. Using image analysis software, we took all histomorphometric measurements of the nerve sections. Based on this anatomical study, the proximal FDS branch was transferred directly to the ECRB branch without nerve graft in 2 patients. The average distance from the origin of nerve branches to the interepicondylar line was 3.5 and 2.3 cm, respectively, for the proximal FDS and ECRB branches. The average length of the proximal FDS branch and ECRB branch was 2.8 and 3.3 cm, respectively. The average number of myelinated nerve fibers of the proximal FDS branch and ECRB branch was 983 and 2,797, respectively. At 2 years' follow-up, preliminary clinical results demonstrated that wrist extension had gained strength against resistance (grade M4). The arc of motion for wrist extension was 30 degrees in the first patient and 70 degrees in the second one. Useful functional recovery was achieved and classified as good result in both cases. The anatomic study and 2 reported results supports our hypothesis that transfer of the proximal FDS branch of median nerve to the ECRB branch of radial nerve could be an alternative method for reconstructiing wrist extension in C5, 6, and 7 avulsion injuries.

Anatomical feasibility of transferring supinator motor branches to the posterior interosseous nerve in C7–T1 brachial plexus palsies

In C7-T1 palsies of the brachial plexus, shoulder and elbow function is preserved, but finger motion is absent. Finger flexion has been reconstructed using tendon or nerve transfers. Finger extension has been restored ineffectively by attaching the extensor tendons to the distal side of the dorsal radius (that is, tenodesis). In these types of nerve palsy, supinator muscle function is preserved because innervation stems from the C-6 root. In the present study, the authors investigated the anatomy and the feasibility of transferring the supinator motor branches to the posterior interosseous nerve. Sacrifice of the supinator motor branches does not abolish supination because biceps muscle function is preserved in lower-type injuries of the brachial plexus. The posterior interosseous nerve was dissected in 20 formalin-fixed forearms. Through posterior forearm access, the posterior interosseous nerve and its motor branches to the supinator muscle were dissected. Specimens were removed for histological study. In the vicinity of the supinator muscle's proximal margin (that is, the Frohse arcade), 2 nerve branches arose laterally and medially from the posterior interosseous nerve to innervate the superficial and deep heads of the supinator muscle, respectively. The supinator motor nerves, when divided, could be coapted directly to the posterior interosseous nerve. The number of myelinated fibers in the supinator motor branches corresponded to 70% that of the posterior interosseous nerve. The supinator motor nerves can be transferred directly to the posterior interosseous nerve to restore thumb and finger extension in patients with C7-T1 brachial plexus lesions.

Experimental study of erythropoietin on promoting sciatic nerve regeneration in rats

Objective To explore the effect of erythropoietin (EPO) on nerve regeneration after sciatic nerve injury and repair in rats and provide experimental basis for clinical treatment of peripheral nerve injury.Methods Forty male Sprague-Dawley rats were randomly divided into two groups, which were named EPO group and NGF group respectively . The sciatic nerve with 10 mm defect was bridged with silicone conduit. Rats of EPO group and NGF group received injection of erythropoietin and nerve growth factor respectively. At 4 and 8 weeks postoperatively, 10 rats from each group were subject to sciatic functional index (SFI), motor nerve conduction velocity (MNCV) and histomorphometric evaluation and immunohistochemical staining of protein gene product 9. 5 (PGP 9. 5) to assess the effect of erythropoietin on rat sciatic nerve regeneration. Results Four weeks after the operation , SFI was - 78.85 + 3.87 in EPO group and - 79.98 ± 4.58 in NGF group. There was no significant difference between the two groups( P > 0.05). Eight weeks postoperatively , SFI was - 60.26±2.91 in EPO group and -64.65 ± 4.11 in NGF group, with significant difference between the two groups( P <0.05). Four and eight weeks after the operation, MNCV, the number of myelinated nerve fibers, the mean optical density and the integration optical, density of PGP 9.5-immtive nerve fibers were significantly higher in EPO group than in NGF group (P < O. 05). Conclusion Erythropoietin can improve nerve regeneration after sciatic nerve injury and repair in rats. Key words: Sciatic nerve; Injuries; Nerve regeneration; Etythropoietin

Regeneration of peripheral nerve after transplantation of CD133+ cells derived from human peripheral blood

Despite intensive efforts in the field of peripheral nerve injury and regeneration, it remains difficult to achieve full functional recovery in humans following extended peripheral nerve lesions. In this study, the authors examined the use of blood-derived CD133(+) cells in promoting the repair of peripheral nerve defects. The authors transplanted phosphate-buffered saline (control), mononuclear cells, or CD133(+) cells embedded in atelocollagen gel into a silicone tube that was used to bridge a 15-mm defect in the sciatic nerve of athymic rats (12 animals in each group). At 8 weeks postsurgery, molecular, histological, and functional evaluations were performed in regenerated tissues. The authors found that sciatic nerves in which a defect had been made were structurally and functionally regenerated within 8 weeks after CD133(+) cell transplantation. From macroscopic evaluation, massive nervelike tissues were confirmed only in rats with CD133(+) cell transplantation compared with the other groups. Morphological regeneration in the samples after CD133(+) cell transplantation, as assessed using toluidine blue staining, was enhanced significantly in terms of the number of myelinated fibers, axon diameter, myelin thickness, and percentage of neural tissue. Compound muscle action potentials were observed only in CD133(+) cell-treated rats. Furthermore, it was demonstrated that the transplanted CD133(+) cells differentiated into Schwann cells by 8 weeks after transplantation. The results show that CD133(+) cells have potential for enhancement of histological and functional recovery from peripheral nerve injury. This attractive cell source could be purified easily from peripheral blood and could be a feasible autologous candidate for peripheral nerve injuries in the clinical setting.

Processed allografts and type I collagen conduits for repair of peripheral nerve gaps

Autografting is the gold standard in the repair of peripheral nerve injuries that are not amenable to end-to-end coaptation. However, because autografts result in donor-site defects and are a limited resource, an effective substitute would be valuable. In a rat model, we compared isografts with Integra NeuraGen (NG) nerve guides, which are a commercially available type I collagen conduit, with processed rat allografts comparable to AxoGen's Avance human decellularized allograft product. In a 14-mm sciatic nerve gap model, isograft was superior to processed allograft, which was in turn superior to NG conduit at 6 weeks postoperatively (P < 0.05 for number of myelinated fibers both at midgraft and distal to the graft). At 12 weeks, these differences were no longer apparent. In a 28-mm graft model, isografts again performed better than processed allografts at both 6 and 22 weeks; regeneration through the NG conduit was often insufficient for analysis in this long graft model. Functional tests confirmed the superiority of isografts, although processed allografts permitted successful reinnervation of distal targets not seen in the NG conduit groups. Processed allografts were inherently non-immunogenic and maintained some internal laminin structure. We conclude that, particularly in a long gap model, nerve graft alternatives fail to confer the regenerative advantages of an isograft. However, AxoGen processed allografts are superior to a currently available conduit-style nerve guide, the Integra NeuraGen. They provide an alternative for reconstruction of short nerve gaps where a conduit might otherwise be used.

Local delivery of glial cell line–derived neurotrophic factor improves facial nerve regeneration after late repair

Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

Focal adhesion kinase (FAK): A regulator of CNS myelination

The formation of the myelin sheath is a crucial step during development because it enables fast and efficient propagation of signals within the limited space of the mammalian central nervous system (CNS). During the process of myelination, oligodendrocytes actively interact with the extracellular matrix (ECM). These interactions are considered crucial for proper and timely completion of the myelin sheath. However, the exact regulatory circuits involved in the signaling events that occur between the ECM and oligodendrocytes are currently not fully understood. Therefore, in the present study we investigated the role of a known integrator of cell-ECM signaling, namely, focal adhesion kinase (FAK), in CNS myelination via the use of conditional (oligodendrocyte-specific) and inducible FAK-knockout mice (Fak(flox/flox): PLP/CreER(T) mice). When inducing FAK knockout just prior to and during active myelination of the optic nerve, we observed a significant reduction in the number of myelinated fibers on postnatal day 14. In addition, our data revealed a decreased number of primary processes extending from oligodendrocyte cell bodies at this postnatal age and on induction of FAK knockout. In contrast, myelination appeared normal on postnatal day 28. Thus, our data suggest that FAK controls the efficiency and timing of CNS myelination during its initial stages, at least in part, by regulating oligodendrocyte process outgrowth and/or remodeling.

A preliminary study, using electron and light-microscopic methods, of axon numbers in the fornix in autopsies of patients with temporal lobe epilepsy

Our objective was to show morphological changes of the fornix in autopsies of patients with temporal lobe epilepsy, which may potentially serve for post-mortem diagnosis. Epileptic and non-epileptic autopsy brains were obtained from the council of forensic medicine between the years 2005 and 2007. In both non-epileptic and epileptic autopsies the mean cross-sectional areas and fiber densities of the right and left fornices were calculated and analyzed. The numbers of myelinated and unmyelinated fibers, and the total number of fibers forming each fornix were counted. The total number of fibers in the right fornix was always greater than in the left fornix, in both epileptic and non-epileptic autopsies. The mean total number of fornix fibers was significantly reduced in epileptics compared with non-epileptics, in both the right (p = 0.043) and left (p = 0.043) sides. The electron-microscopic sections showed that myelinated axons outnumbered unmyelinated axons in both epileptic and non-epileptic autopsies. However, the reduction in the number of unmyelinated fibers was only statistically significant for the right fornix in right epileptic autopsies (p = 0.021). Although the reduction in the number of myelinated fibers was not statistically significant, electron-microscopic evaluations showed myelin degeneration of the myelinated fibers in the right fornix of the right temporal lobe in epileptic autopsies. In conclusion, our results suggest that unmyelinated fiber loss is functionally important, and may have functional consequences of diagnostic value.

Sciatic nerve regeneration is accelerated in galectin-3 knockout mice

The success of peripheral nerve regeneration depends on intrinsic properties of neurons and a favorable environment, although the mechanisms underlying the molecular events during degeneration and regeneration are still not elucidated. Schwann cells are considered one of the best candidates to be closely involved in the success of peripheral nerve regeneration. These cells and invading macrophages are responsible for clearing myelin and axon debris, creating an appropriate route for a successful regeneration. After injury, Schwann cells express galectin-3, and this has been correlated with phagocytosis; also, in the presence of galectin-3, there is inhibition of Schwann-cell proliferation in vitro. In the present study we explored, in vivo, the effects of the absence of galectin-3 on Wallerian degeneration and nerve-fiber regeneration. We crushed the sciatic nerves of galectin-3 knockout and wild-type mice, and followed the pattern of degeneration and regeneration from 24 h up to 3 weeks. We analyzed the number of myelinated fibers, axon area, fiber area, myelin area, G-ratio and immunofluorescence for β-catenin, macrophages and Schwann cells in DAPI counterstained sections. Galectin-3 knockout mice showed earlier functional recovery and faster regeneration than the wild-type animals. We concluded that the absence of galectin-3 allowed faster regeneration, which may be associated with increased growth of Schwann cells and expression of β-catenin. This would favor neuron survival, followed by faster myelination, culminating in a better morphological and functional outcome.

Metabotropic GABA-B receptors in the PNS: role in nociception and myelination

Event Abstract Back to Event Metabotropic GABA-B receptors in the PNS: role in nociception and myelination Valerio Magnaghi1*, M. Ballabio1, B. Bettler2, A. Faroni1 and P. Procacci3 1 University of Milan, Department of Endocrinology, Italy 2 University of Basel, Department of Biomedicine, Switzerland 3 University of Milan, Department of Human Morphology, Italy Metabotropic GABA-B receptors are present in the CNS where they play important roles in the modulation of nociceptive transmission and pain. Many preclinical studies reported that the GABA-B specific agonist baclofen is antinociceptive in different models of acute and chronic pain. The study of GABA-B1 knockout mice further supports the contribution of GABA-B receptors to central nociceptive processing. These mice are hyperalgesic, showing a reduced latency to thermal and mechanical stimuli. A tonic GABA-B receptor activation therefore appears to contribute to the establishment of the nociceptive threshold. Interestingly, GABA-B receptors are expressed in the peripheral nervous system (PNS), mainly in the Schwann cells where they control cell proliferation and myelination. Emerging evidence obtained in GABA-B1 knockout mice indicates that these mice exhibit gait alterations and reduced allodynic sensitivity too. Furthermore, GABA-B1-deficient mice show morphological and molecular changes in peripheral nerves, including an increase in the number of small myelinated fibers, as well as in small neurons of the lumbar dorsal root ganglia. These fibers are supposed to be A_ nociceptive fibers. Consequently, it has been suggested that GABA-B receptors are implicated in the PNS myelination process. The possibility that PNS alterations contribute to the sensory phenotypes observed in GABAB1- deficient mice has been also hypothesized. The study in conditional mice that specifically lack the GABA-B1 receptor in the Schwann cells or in motoneurons will aim to clarify the role of GABA-B receptors in peripheral pain sensitivity. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 04 – Dis-inhibition processes in pain sensitization Citation: Magnaghi V, Ballabio M, Bettler B, Faroni A and Procacci P (2009). Metabotropic GABA-B receptors in the PNS: role in nociception and myelination. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.019 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Nov 2009; Published Online: 19 Nov 2009. * Correspondence: Valerio Magnaghi, University of Milan, Department of Endocrinology, Milan, Italy, valerio.magnaghi@unimi.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Valerio Magnaghi M. Ballabio B. Bettler A. Faroni P. Procacci Google Valerio Magnaghi M. Ballabio B. Bettler A. Faroni P. Procacci Google Scholar Valerio Magnaghi M. Ballabio B. Bettler A. Faroni P. Procacci PubMed Valerio Magnaghi M. Ballabio B. Bettler A. Faroni P. Procacci Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.