Tibial Nerve Repair in a Dog Model: Effect of Local and Systemic Administration of Erythropoietin.

PURPOSE: This study aimed to assess the effectiveness of erythropoietin (EPO) as a novel treatment for peripheral nerve injury after surgical repair of an induced tibial nerve injury in dogs. METHODS: Mongrel dogs (n = 27) were randomly divided into three equal groups. A complete tibial nerve injury was induced and repaired directly by stay sutures and the local application of 1 mL fibrin glue (control group). In the "systemic" group, 20,000 IU of EPO were given subcutaneously immediately after surgery and on the first and second days after surgery. In the "local" group, EPO was mixed with fibrin glue at 1,000 IU/mL. Lameness score, compound muscle action potential of the tibial nerve, and serum biochemical and histopathological examinations were performed to evaluate the treated dogs over the study period (12 weeks). RESULTS: EPO significantly improved the lameness score and compound muscle action potential in both the systemic and local groups. After 12 weeks, systemic and local groups showed earlier improvement in lameness, reaching scores of -1 and 0, respectively, in comparison with the control group, which did not reach a score of -1. The histological study revealed a normal architecture of the nerve bundles within connective tissue. The axons were aligned in a regular pattern, whereas the control group had disrupted and degenerated nerve axons with large gaps in between. CONCLUSIONS: EPO has an accelerating healing effect after tibial nerve surgical repair. Local EPO mimics systemic EPO treatment without systemic adverse effects. These findings indicated that EPO has a potential role in tibial nerve recovery and nerve regeneration. CLINICAL RELEVANCE: The findings of the present experimental study supported the beneficial effects of systemic and local EPO when combined with peripheral nerve surgical repair, potentially improving functional outcomes and enhancing faster recovery.

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model.

Calpain activation has been implicated in various pathologies, including neurodegeneration. Thus, calpain inhibition could effectively prevent spinal cord injury (SCI) associated with neurodegeneration. In the current study, a dog SCI model was used to evaluate the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) as an anti-inflammatory drug. SCI was experimentally induced in sixteen mongrel dogs through an epidural balloon compression technique. The dogs were allocated randomly into four groups: control, MPSS, PD150606, and MPSS+PD150606. Clinical evaluation, serum biochemical, somatosensory evoked potentials, histopathological, and immunoblotting analyses were performed to assess treated dogs during the study. The current findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group and to a lesser extent in MPSS or PD150606 treatment alone. Interestingly, the combined treatment effectively inhibited the calpain-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

Assessment of angiotensin converting enzyme gene polymorphism in patients with psoriasis.

Psoriatic patients had diversity of clinical presentations and complications. Psoriasis can have significant interference with the patient's quality of life, recovery, and outcome. Some evidences suggest that the angiotensin converting enzyme (ACE) is present in the skin of psoriatic patients. This study intended to assess the patterns of ACE insertion/deletion (ACE ID) polymorphism and the levels of serum ACE among psoriatic patients in comparison to normal controls. The study included two groups: 20 patients with psoriasis and 20 apparently healthy adults with negative family history of psoriasis as a control group. Psoriasis area and severity index (PASI) was used to measure of severity of psoriasis. In both groups, ACE ID gene polymorphism was assessed by quantitative real-time polymerase reaction and serum ACE levels was evaluated using an enzyme-linked immunosorbent assay. ACE ID genotype was significantly higher among the psoriatic group in comparison to the control group (40.0% versus 15.0%, respectively, p=0.016). D allele was significantly higher among the psoriatic group than the control group (25.0% versus 7.5%, respectively, p=0.034). ACE ID genotype carried significantly higher risk in psoriatic group versus control group (OR=3.8). The D allele carried higher risk in psoriatic group versus control group (OR=4.1). ACE serum levels were significantly higher among the psoriatic group compared to the control group (87.4±7.03 versus 2.3±0.7, respectively; p < 0.001). We concluded that ACE ID gene polymorphism may be considered as a risk factor for developing psoriasis.

Association of CD40 rs1883832 Polymorphism with Susceptibility of Diabetic Nephropathy and Neuropathy in Egyptian Population.

Diabetic nephropathy (DN) and peripheral neuropathy (DPN) are unpredictable diabetic complications with narrow management alternatives. CD40-CD40 ligand system may be an essential pathway for diabetic microvascular complications. No previous studies had evaluated the relationship between CD40 rs1883832 polymorphism and DN/DPN. This study aimed to investigate the association between CD40 rs1883832 polymorphism and the risk of nephropathy and neuropathy in Egyptian patients with type 2 diabetes mellitus. A total of 106 diabetic patients (53 with nephropathy and 53 with neuropathy) and 53 healthy controls (without DM or other overt chronic conditions) were recruited from Suez Canal University Hospitals. Genotyping of CD40 gene polymorphisms was carried out using the polymerase chain reaction-restriction fragment length polymorphism assay. Patients with TT genotype and T allele carry a higher risk of developing DN (odds ratio (OR)=5.40, P=0.0026) and OR=2.56, P=0.0009, respectively). Likewise, the risk of DPN was significantly higher in patients carrying TT genotype (OR=2.91, P=0.045) and T allele (OR=1.84, P=0.028), respectively. In conclusions, the T allele is significantly associated with DN and DPN. Further studies with larger sample sizes are necessary to confirm our observations.

Intercostal, ilioinguinal, and iliohypogastric nerve transfers for lower limb reinnervation after spinal cord injury: an anatomical feasibility and experimental study.

OBJECTIVESpinal cord injury (SCI) has been investigated in various animal studies. One promising therapeutic approach involves the transfer of peripheral nerves originating above the level of injury into those originating below the level of injury. The purpose of the present study was to evaluate the feasibility of nerve transfers for reinnervation of lower limbs in patients suffering SCI to restore some hip and knee functions, enabling them to independently stand or even step forward with assistive devices and thus improve their quality of life.METHODSThe feasibility of transferring intercostal to gluteal nerves and the ilioinguinal and iliohypogastric nerves to femoral nerves was assessed in 5 cadavers. Then, lumbar cord hemitransection was performed below L1 in 20 dogs, followed by transfer of the 10th, 11th, and 12th intercostal and subcostal nerves to gluteal nerves and the ilioinguinal and iliohypogastric nerves to the femoral nerve in only 10 dogs (NT group). At 6 months, clinical and electrophysiological evaluations of the recipient nerves and their motor targets were performed.RESULTSThe donor nerves had sufficient length to reach the recipient nerves in a tension-free manner. At 6 months postoperatively, the mean conduction velocity of gluteal and femoral nerves, respectively, increased to 96.1% and 92.8% of the velocity in controls, and there was significant motor recovery of the quadriceps femoris and glutei.CONCLUSIONSIntercostal, ilioinguinal, and iliohypogastric nerves are suitable donors to transfer to the gluteal and femoral nerves after SCI to restore some hip and knee motor functions.