Akimasa Morita

Nerve growth factor signaling of p75 induces differentiation and ceramide-mediated apoptosis in Schwann cells cultured from degenerating nerves

In peripheral nerve regeneration or remyelination, immature Schwann cells expressing p75NTR play cardinal roles in the support and regeneration of axons (Griffin JW, Hoffman PN. Peripheral Neuropathy 361–376, 1993). Only one of four to six Schwann cells participate in remyelination of damaged or regenerating axons. The rest of the cells, or supernumerary Schwann cells, show severe atrophy and gradually decrease in number, reestablishing a 1:1 axon–Schwann cell relationship (Said G, Duckett S. Acta Neuropathol (Berl) 53:173–179, 1981). Recent reports demonstrated that severely atrophied supernumerary Schwann cells are eliminated by apoptosis during axonal regeneration or remyelination (Hirata H, Hibasami H. Apoptosis 3:353–360, 1998; Berciano MT, Calle E. Acta Neuropathol (Berl) 95:269–279, 1998). The mechanism to induce selective death of supernumerary Schwann cells without causing any damage to axon‐associated Schwann cells or axons remains to be determined. In this article, we report that p75NTR, the low‐affinity receptor for all members of neurotrophins, signals both cell differentiation and apoptosis through intracellular ceramide elevation. The final response is dependent on the intracellular ceramide level and Schwann cells modulate their response by changing expression level of p75NTR. This effect was selective for nerve growth factor (NGF). Taken together, the present study suggests that NGF contributes both to phenotypic regulation and to elimination of the dedifferentiated Schwann cells, while supporting survival or regeneration of certain types of axons during peripheral nerve repair or regeneration. GLIA 36:245–258, 2001.

MMP-2 expression is associated with rapidly proliferative arteriosclerosis in the flexor tenosynovium and pain severity in carpal tunnel syndrome.

Due to the lack of correlation between symptom severity and electrophysiology or nerve function, the ‘container hypothesis’ has emerged as a new concept in carpal tunnel syndrome (CTS). This proposes that symptoms relate to connective tissue alteration rather than to nerve fibre pathology. This study was conducted to investigate the pathology of the flexor tenosynovium and its relationship with symptomatology. The subjects comprised 40 patients with electrophysiologically proven CTS who underwent open carpal tunnel release (age range: 31–79 years). In all patients, subjective symptom severity was assessed with a Likert scale and symptom duration was recorded preoperatively. Flexor tenosynovium biopsied during surgery was analysed for arterial and connective tissue alteration. Proliferative arteriosclerosis was graded using the modified Banff score. Gelatin zymography and immunohistochemistry were also performed to investigate the role of gelatinase in CTS. Relationships were evaluated using Spearman rank correlation coefficients. Proliferative arteriosclerosis occurred with disease progression in the flexor tenosynovium, in the absence of inflammation. This event did not correlate with patient age but correlated closely with symptom duration. Immunohistochemistry with antibodies against MMP‐2 and elastic van Gieson staining revealed that arterioles express high levels of MMP‐2 within 3 months of symptom onset and that intimal hyperplasia proceeded rapidly between 4 and 7 months, resulting in severe vascular narrowing. Gelatin zymography showed that MMP‐2 activity correlated negatively with symptom duration and positively with pain severity. Copyright

Functional Recovery of the Donor Knee After Autologous Osteochondral Transplantation for Capitellar Osteochondritis Dissecans

Background: Osteochondral autograft transplantation has been advocated to treat severe osteochondritis dissecans of the humeral capitellum in throwing athletes to reproduce the normal hyaline cartilage and achieve long-term elbow function. Although some authors have reported good outcomes, the current authors are concerned about functional recovery of the donor knee after osteochondral grafts have been harvested. Purpose: The present prospective study analyzed functional recovery of the donor knee after osteochondral graft harvest. Study Design: Case series; Level of evidence, 4. Methods: Twelve male patients (average age at surgery, 14.4 years) had severe osteochondritis dissecans of the humeral capitellum treated with osteochondral autograft transplantation from the contralateral knee joint. The donor knee of each patient was assessed for pain (visual analog scale), joint effusion, Lysholm score, radiographic findings, and muscle strength (60 and 180 deg/sec). Results: At 3 months after surgery, 10 patients were pain-free (visual analog scale score, 0); none had knee joint effusion; and 10 gained 100 points in the Lysholm score. However, muscle power (60 deg/sec) of the knee extensor revealed 8 patients with reduced muscle strength at 3 months compared with the preoperative level, although 11 patients reached preoperative knee extensor muscle strength at 12 months. Radiographic findings at 24 months showed that none of the patients had knee osteoarthritis. Conclusion: A time lag was evident in recovery between postoperative symptoms and muscle power at 3 months. However, harvesting osteochondral grafts did not exert adverse effects on donor knee function in young athletes at 2 years after undergoing osteochondral autograft transplantation for capitellar osteochondritis dissecans.

Palmar bowing of the flexor retinaculum on wrist MRI correlates with subjective reports of pain in carpal tunnel syndrome

To investigate the utility of palmar bowing of the flexor retinaculum (PBFR) on magnetic resonance imaging (MRI) as an adjunct to presurgical evaluation of carpal tunnel syndrome (CTS).

Differentiation and apoptosis without DNA fragmentation in cultured Schwann cells derived from wallerian-degenerated nerve

The Schwann cell cables provide particularly favorable sites for the growth of regenerating axonal sprouts. However, if they remain denervated, endoneurial fibrosis takes place with the Schwann cells atrophying and total Schwann cell number gradually decrease with time. Even when regenerating axonal sprouts invade into the cables, Schwann cells do not survive for long periods if they fail to make axonal contact. These observations strongly suggest the involvement of apoptosis in peripheral nerve degeneration and regeneration. So, we investigated the behavior of Schwann cells prepared from walleriandegenerated adult rat sciatic nerve in vitro. The secondary cultured Schwann cells showed serial changes in morphology, mitotic activity and migratory activity as they do during Schwann cell cable formation in vivo. At the final stage of differentiation, the Schwann cells became rounded and detached from the flask with extensive blebbing. Electron micrographs clearly demonstrated typical cytoplasmic changes of apoptosis, but, nuclei of most of the cells retained their size and morphology with residual nucleolar structures. An agarose gel electrophoresis of DNA clearly demonstrated that there was not any DNA fragmentation up to 120 h after detachment. Results by in situ apoptosis detection assay did not show any DNA degradation despite the substantial decrease in Schwann cell number. In conclusion, during peripheral nerve degeneration and regeneration, supernumerary Schwann cells are removed by apoptosis, however, it lacks most of the nuclear events of usual apoptosis.

Transient damage to the axonal transport system without Wallerian degeneration by acute nerve compression.

The aim of this study was to examine whether acute nerve compression damages an axonal transport system based on microtubules and how the fibers recover after the compression. A 5-mm segment of the tibial nerve of male wistar rat was compressed with a specially designed clip. Functional recovery was assessed using Tibial Nerve Functional Index (TFI). Rats were sacrificed each day from Day 0 to Day 2 and every 2 days between Day 4 and Day 10. For immunohistochemical analysis of the tibial nerve, the proximal uncompressed, the middle compressed, and the distal uncompressed segments of each section were assessed under immunofluoroscent microscopy for anti-dynein, anti-tubulin, and anti-neurofilament antibodies staining. In rats whose tibial nerve was compressed by 25 g/mm2 of pressure for 5 min, staining of dynein and mirotubules in the compressed portion were obscure on Days 4-8, suggesting that the microtubules based axonal transport system was temporarily damaged, while neurofilaments were retained. In contrast, in the distal portion, anti-neurofilament staining showed no abnormality throughout the experimental period, indicating that Wallerian degeneration did not occur. We conclude that acute nerve compression can cause transient damage to the axonal transport system in nerve fibers without Wallerian degeneration.

Congenital Triggering of The Index Finger at The A2 Pulley

A case of trigger index finger is reported. The diagnosis was made in the neonatal intensive care unit. The proximal interphalangeal joint (PIP) was locked in a flexed position. A nodular thickening of the flexor tendon was felt at the A2 pulley level. Surgery revealed thickening of both the A2 pulley and the radial slip of the flexor superficialis tendon. Division of the A2 pulley released the PIP joint locking.

Enhanced reinnervation after neurotization with Schwann cell transplantation

We investigated the feasibility of using Schwann cell transplantation to enhance reinnervation after direct nerve‐to‐muscle neurotization (NMN). The denervated anterior tibial muscle was neurotized by tibial nerve implantation, and Schwann cell suspension (transplantation group) or an equivalent volume of culture medium (control group) was injected at the implantation site. In the control group, few axons invaded the muscle, demonstrating that skeletal muscle was poorly permissive to the advancement of axons. In the transplantation group, a large number of regenerating axons grew for a longer distance throughout the muscle, and reinnervated motor endplates were significantly more abundant. Enhanced reinnervation and functional recovery of the muscle in the transplantation group was confirmed by a significant increase in the compound muscle action potential and in muscle weight. These results suggest that intramuscular Schwann cell transplantation has potential as a cell therapy to improve functional recovery after NMN. Muscle Nerve, 2005

Long-Term follow up of patients with conservatively treated Kienböck's disease

Seventeen patients with unilateral conservatively treated Kienböcks disease who had been followed up for more than 10 years were studied. We examined pain, range of wrist motion, grip strength, radiological staging, Ståhl index, and clinical results. At the time of final follow up, none of the patients complained of pain severe enough to keep them from working. The flexion/extension arc was less than 60 degrees in only 1 patient. As for radiological changes, five wrists remained in the same category of the Lichtmans staging system4 throughout the follow-up period, while eight progressed to higher categories. The remaining four wrists showed radiological improvement. Clinical results were good in 10 patients, fair in 4, and poor in 3. The overall results were better than those reported in other studies of conservatively treated Kienböcks disease with shorter follow-up periods1,3,7,9. These results strongly suggest that Kienböcks disease has the capacity to heal spontaneously in the long run. Surgical treatment that accelerates healing should be employed, rather than excision or excision/replacement of the lunate.

Pathomechanical Significance of Radial Head Subluxation in the Onset of Osteochondritis Dissecans of the Radial Head

Osteochondritis dissecans of the elbow mainly involves the capitellum; however, no authors have reported the condition in the radial head with subluxation of the radial head. We report four cases in which osteochondritis dissecans involved the radial head and was accompanied by radial head subluxation. All patients were male and their ages ranged from 11 to 13 years (average, 11.8 years). All lesions were located at the posteromedial aspect of the radial head with anterior subluxation of the radial head. Fragment removal was performed in one case and ulnar osteotomy in two cases; the remaining case was treated conservatively with the prohibition of sports. Three cases had a good outcome, whereas obvious anterior subluxation of the radial head and limitation of elbow flexion remained in the case treated with fragment removal.