Application of 4-(aminomethyl)cyclohexanecarboxylic acid (tranexamic acid; TAMCA) to the central nervous system (CNS) has been shown to result in hyperexcitability and convulsions. However, the mechanisms underlying this action are unknown. In the present study, we demonstrate that TAMCA binds to the ␥-aminobutyric acid (GABA) binding site of GABA A receptors in membranes from rat cerebral cortex and does not interfere with N-methyl-D-aspartate receptors. Patch-clamp studies using human embryonic kidney cells transiently transfected with recombinant GABA A receptors composed of ␣1␤2␥2 subunits showed that TAMCA did not activate these receptors but dose dependently blocked GABA-induced chloride ion flux with an IC 50 of 7.1 Ϯ 3.1 mM. Application of TAMCA to the lumbar spinal cord of rats resulted in dose-dependent hyperexcitability, which was completely blocked by coapplication of the GABA A receptor agonist muscimol. These results indicate that TAMCA may induce hyperexcitability by blocking GABA-driven inhibition of the CNS.

De-focused low energy extracorporeal shock wave therapy (ESWT) has been widely used in various clinical and experimental models for the treatment of painful conditions such as epicondylitis and plantar fascitis and also bone and wound healing. There is evidence that ESWT improves the metabolic activity of various cell types, e.g. chondrocytes and endothelial cells but little is known about its effects on nervous tissue. The aim of this study was to investigate whether ESWT improves the regeneration of injured nerves in an experimental rat model. Sprague-Dawley rats received an 8mm long homotopic nerve autograft into the right sciatic nerve, fixed with epineurial sutures. Two experimental groups were set up: the group 1 animals received ESWT (300 impulses, 3 Hz) immediately after nerve grafting whereas the group 2 (control) animals received only nerve autografts. Serial CatWalk automated gait analysis, electrophysiological studies and morphological investigations were carried out. The survival time was either 3 weeks or 3 months. At 6 to 8 weeks of survival the ESWT group of animals exhibited a significantly improved functional recovery relative to the controls. Electrophysiological observations at 3 weeks after surgery revealed marked values of amplitude (3.9±0.8 mV, S.E.M.) and compound nerve action potential (CNAP, 5.9±1.4 mV·ms, S.E.M.) in the ESWT group, whereas there were no detectable amplitudes in the control group. This finding was accompanied by significantly greater numbers of myelinated nerve fibres in the middle of the graft (4644±170 [S.E.M., ESWT] vs 877±68 [S.E.M., control]) and in the distal stump (1586±157 [S.E.M., ESWT] vs 308±29 [S.E.M., control]) of ESWT animals relative to the controls 3 weeks after surgery. Three weeks after surgery the nerve grafts of control animals contained great numbers of phagocytes and unmyelinated nerve fibres, while the ESWT nerve grafts were filled with well-myelinated regenerating axons. There was no significant difference between the numbers of endoneural vessels in the ESWT and the control nerves. Three months after surgery, no significant differences were observed in the functional and electrophysiological data. Equally high numbers of myelinated axons distal to the graft could be found in both groups (7693±673 [S.E.M., ESWT] vs 6090±716 [S.E.M., control]). These results suggest that ESWT induces an improved rate of axonal regeneration, this phenomenon probably involving faster Wallerian degeneration, the improved removal of degenerated axons and a greater capacity of the injured axons to regenerate.

Full range of motion mobilization may impede functional nerve recovery by significant endoneural collagenization and decreased angiogenesis at the nerve suture segment. Complete alleviation of in situ (pathophysiologic) tension at the nerve suture site seems to improve functional peripheral nerve regeneration.

We conclude that microCT with 3D reconstruction is the optimal method diagnostic tool in fracture healing, especially in nonunion. Furthermore, direct coverage of the fracture site by muscle flaps results in a mineralized enhanced bone formation within the osteotomy site (i.e. within the gap). Skeletal muscle coverage hypothetically might have osteogenic augmentation potential, thus being able to prevent pseudoarthrosis.