Peripheral nerve morphogenesis induced by scaffold micropatterning

Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous micro-structure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold's micro-structure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration.     

Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease

Journal of Neurology - To investigate the prognostic role and the major determinants of serum phosphorylated neurofilament heavy -chain (pNfH) concentration across a large cohort of motor neuron...     

The role of transcranial Doppler in carotid artery surgery.

In order to evaluate the usefulness of transcranial Doppler (TCD) in carotid artery surgery, 90 patients who underwent carotid endarterectomy were studied. Transcranial Doppler was performed preoperatively with digital compression of the carotid artery and intraoperatively at the time of cross-clamping, together with routine EEG monitoring. The percentage residual middle cerebral artery velocity (%MCAV) during carotid artery compression or cross-clamping was considered. The intraoperative %MCAV at cross-clamping was compared with the values obtained in the preoperative examination during the compression test and with the EEG data; the EEG records were blindly reviewed by a neurologist and divided into three groups: group A, normal; group B, moderate anomalies and group C, major anomalies. There were no significant differences between preoperative %MCAV (compression test) and intraoperative %MCAV (cross-clamping) by separate analysis of the data related to systolic, diastolic and mean velocity. The systolic, diastolic, mean %MCAV and the Gosling index after cross-clamping were then compared with the EEG data: no significant differences were seen between groups A and B; on the other hand, in all patients with major EEG anomalies (group C) the %MCAV at TCD was reduced to 0. In conclusion, preoperative TCD associated with carotid artery compression appears a safe and useful way of identifying patients at risk of cerebral ischaemia during carotid artery cross-clamping. Patients with no residual flow at intraoperative TCD need to be considered as presenting a very high risk of ischaemia and in this group the use of a shunt is mandatory.     

Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock

IntroductionPlatelet mitochondrial respiratory chain enzymes (that produce energy) are variably inhibited during human sepsis. Whether these changes occur even during other acute critical illness or are associated with impaired platelet aggregation and secretion (that consume energy) is not known. The aims of this study were firstly to compare platelet mitochondrial respiratory chain enzymes activity between patients with sepsis and those with cardiogenic shock, and secondly to study the relationship between platelet mitochondrial respiratory chain enzymes activity and platelet responsiveness to (exogenous) agonists in patients with sepsis.MethodsThis was a prospective, observational, case–control study. Platelets were isolated from venous blood of 16 patients with severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet mitochondrial respiratory chain enzymes activity was measured with spectrophotometry and expressed relative to citrate synthase activity, a marker of mitochondrial density. Platelet aggregation and secretion in response to adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating peptide were measured with lumiaggregometry only in patients with sepsis. In total, 16 healthy volunteers acted as controls for both spectrophotometry and lumiaggregometry.ResultsPlatelets of patients with sepsis or cardiogenic shock similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and complex IV (P < 0.001) activity than those of controls. Platelets of patients with sepsis were generally hypo-responsive to exogenous agonists, both in terms of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial NADH (R² 0.36; P < 0.001), complex I (R² 0.38; P < 0.001), complex I and III (R² 0.27; P = 0.002) and complex IV (R² 0.43; P < 0.001) activity was associated with lower first wave of aggregation with ADP.ConclusionsSeveral platelet mitochondrial respiratory chain enzymes are similarly inhibited during human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial dysfunction is associated with general platelet hypo-responsiveness to exogenous agonists.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00541827","term_id":"NCT00541827"}}NCT00541827. Registered 8 October 2007.     

Neurocognitive profiles in Duchenne muscular dystrophy and gene mutation site

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing.     

Balance exercise in patients with chronic sensory ataxic neuropathy: a pilot study

Although exercise therapy is considered part of the treatment of neuropathic patients, and somatosensory input is essential for motor learning, performance and neural plasticity, rehabilitation of patients with sensory ataxia has received little attention so far. The aim of this prospective pilot study was to explore the short‐ and medium‐term efficacy of a 3‐week intensive balance and treadmill exercise program in chronic ataxic neuropathy patients; 20 consecutive patients with leg overall disability sum score (ODSS‐leg) ≥2, absent/mild motor signs, clinical and therapeutic stability ≥4 months were enrolled. Evaluations were done at baseline, at the end of treatment and at 3‐ and 6‐month follow‐up. Outcome measurements included: ODSS‐leg, Berg balance scale, 6‐min walk distance, and the functional independence measure (FIM) scale. The short‐form‐36 health status scale (SF‐36) was used to measure health‐related quality of life (HRQoL). ODSS‐leg improved significantly compared with baseline, 3 weeks, 3 months (primary outcome), and 6 months follow‐up. A significant improvement in all functional secondary outcome measurements and in some SF‐36 subscales was also observed. This pilot study suggests that balance exercise is safe and well tolerated and might be effective in ameliorating disability and HRQoL in patients with chronic peripheral sensory ataxia.