Dexamethasone prevents vascular damage in earlystage non-freezing cold injury of the sciatic nerve

Non-freezing cold injury is a prevalent cause of peripheral nerve damage, but its pathogenic mechanism is poorly understood, and treatment remains inadequate. Glucocorticoids have anti-inflammatory and lipid peroxidation-inhibiting properties. We therefore examined whether dexamethasone, a synthetic glucocorticoid compound, would alleviate early-stage non-freezing cold injury of the sciatic nerve. We established Wistar rat models of non-freezing cold injury by exposing the left sciatic nerve to cold（3–5°C） for 2 hours, then administered dexamethasone（3 mg/kg intraperitoneally） to half of the models. One day after injury, the concentration of Evans blue tracer in the injured sciatic nerve of rats that received dexamethasone was notably lower than that in the injured sciatic nerve of rats that did not receive dexamethasone; neither Evans blue dye nor capillary stenosis was observed in the endoneurium, but myelinated nerve fibers were markedly degenerated in the injured sciatic nerve of animals that received dexamethasone. After dexamethasone administration, however, endoneurial vasculopathy was markedly improved, although damage to the myelinated nerve fiber was not alleviated. These findings suggest that dexamethasone protects the blood-nerve barrier, but its benefit in non-freezing cold injury is limited to the vascular system.

Mice lacking perforin have improved regeneration of the injured femoral nerve

The role that the immune system plays after injury of the peripheral nervous system is still not completely understood.Perforin,a natural killer cell-and T-lymphocyte-derived enzyme that mediates cytotoxicity,plays important roles in autoimmune diseases,infections and central nervous system trauma,such as spinal cord injury.To dissect the roles of this single component of the immune response to injury,we tested regeneration after femoral nerve injury in perforin-deficient(Pfp^(-/-))and wild-type control mice.Single frame motion analysis showed better motor recovery in Pfp^(-/-)mice compared with control mice at 4 and 8 weeks after injury.Retrograde tracing of the motoneuron axons regrown into the motor nerve branch demonstrated more correctly projecting motoneurons in the spinal cord of Pfp^(-/-)mice compared with wild-types.Myelination of regrown axons measured by g-ratio was more extensive in Pfp^(-/-)than in wild-type mice in the motor branch of the femoral nerve.Pfp^(-/-)mice displayed more cholinergic synaptic terminals around cell bodies of spinal motoneurons after injury than the injured wild-types.We histologically analyzed lymphocyte infiltration 10 days after surgery and found that in Pfp^(-/-)mice the number of lymphocytes in the regenerating nerves was lower than in wild-types,suggesting a closed blood-nerve barrier in Pfp^(-/-)mice.We conclude that perforin restricts motor recovery after femoral nerve injury owing to decreased survival of motoneurons and reduced myelination.

Asymmetric limb weakness in Guillain-Barre syndrome:Three case reports

BACKGROUND Guillain-Barrésyndrome(GBS)is an autoimmune-mediated peripheral neuropathy characterized by symmetric weakness.Asymmetric weakness in GBS is uncommon and may be easily confused with other differential diagnoses.We herein present three cases of asymmetric GBS and review the literature on this atypical subtype of GBS in order to describe the characteristics of asymmetric GBS and to provide experience for clinicians.CASE SUMMARY Different from patients in the previous reports,our patients showed persistent asymmetric limb weakness from the onset to recovery phase.All three patients were serologically positive for antecedent infections.Two of the three cases had IgG antibodies against ganglioside GM1.Two patients received immunotherapy including intravenous immunoglobulin and plasma exchange,while one patient received only supportive treatment.Autoantibodies against gangliosides,asymmetry of congenital development of blood-nerve barrier and limb use may contribute to the development of asymmetric limb weakness in GBS.CONCLUSION Asymmetric GBS may be a rare clinical variant and should be considered when a patient develops acute and progressive asymmetric limb weakness.The differences in clinical features and prognosis between asymmetric GBS and classic GBS deserve further investigation in a large study.