Cirugía Ortopedica

The authors use Zancolli's classification for the surgical evaluation of the spastic upper limb. The paper describes the surgical technique used by the authors in the treatment of twenty-six patients grade III, having a "non-functional hand". After justifying the treatment, the technique is described which includes a time for the elbow to relax the antebrachii flexors and M. Epitrochlearis, a time for defunctioning the pronators and relaxing the flexors by intramuscular tenotomy. Transplantation of the flexors of the wrist is carried out to the extensors of the wrist and fingers. The thumb-in-palm is corrected by a tenotomy of the Adductor and Flexor Pollicis Brevis and transplanting the Brachioradialis to the tendons of the first dorsal compartment.

We have investigated the motor changes in rats subjected to a moderate photochemical injury on mid-thoracic (T8) or high lumbar (L2) spinal cord segments. Fourteen days after surgery, L2 injured animals presented gross locomotor deficits (scored 10 ± 2.8 in the BBB scale), decreased amplitude of motor-evoked potentials (MEPs) recorded on tibialis anterior (TA) and plantar (PL) muscles (24% and 6% of the preoperative mean values, respectively), reduced M wave amplitudes (75%, 62%), and also facilitated monosynaptic reflexes evidenced by an increase of the H/M amplitude ratio (158% and 563%). On the other hand, T8 injured animals had only slight deficits in locomotion (18 ± 0.6 in the BBB scale), a minimal reduction in MEP amplitudes (78% and 71% in TA and PL muscles), normal M wave amplitudes, and a milder increase of the H/M ratio in the TA muscle (191%) but less pronounced in the PL muscle (172%). The percentage of spared tissue at the site of injury was similar in both experimental groups (L2: 79% and T8: 82%). Taken together, these results indicate that lumbar spinal injuries have more severe consequences on hindlimb motor output than injuries exerted on thoracic segments. The causes of this anatomical difference may be attributed to damage inflicted on the central pattern generator of locomotion resulting in dysfunction of lumbar motoneurons and altered spinal reflexes modulation.

Disconnection of the axon from the soma of spinal motoneurons (MNs) leads either to a retrograde degenerative process or to a regenerative reaction, depending on the severity and the proximity to the soma of the axonal lesion. The endoplasmic reticulum (ER) is a continuous membranous network that extends from the nucleus to the entire cytoplasm of the neuronal soma, axon and dendrites. We investigated whether axonal injury is sensed by the ER and triggers the activation of protective mechanisms, such as the unfolded protein response (UPR) and autophagy. We found early (at 3 days) accumulation of beclin1, LC3II and Lamp-1, hallmarks of autophagy, in both degenerating MNs after spinal root avulsion and in non-degenerating MNs after distal nerve section, although Lamp-1 disappeared by 5 days only in the former. In contrast, only degenerating MNs presented early activation of IRE1a, revealed by an increase of the spliced isoform of Xbp1 and accumulation of ATF4 in their nucleus, two branches of the UPR, and late BiP downregulation in association with cytoskeletal and organelle disorganization. We conclude that BiP decrease is a signature of the degenerating process, as its overexpression led to an increase in MN survival after root avulsion. Besides, Bcl2 is strongly implicated in the survival pathway activated by BiP overexpression.

We studied the effects of olfactory ensheathing cells (OECs) transplanted in a photochemical spinal cord injury in adult rats. After dorsal laminectomy at T8 vertebra, subjacent spinal cord was bathed with rose Bengal for 10 min and illuminated with visible light by means of an optic fiber connected to a halogen lamp for 2.5 min at maximal intensity of 8 kLux. Eight injured rats received a suspension of OECs in DMEM, and another eight rats received DMEM alone. Locomotor ability scored by the BBB scale, pain sensibility by the plantar algesimetry test, and motor-and somatosensory-evoked potentials by electrophysiological techniques were evaluated for 3 months postsurgery. Finally, all rats were perfused with paraformaldehyde and transverse sections from the spinal cord segment at the lesion site were immunostained against GFAP. Area of the preserved spinal cord parenchyma was measured from the GFAPimmunolabeled cord sections. The BBB score and the amplitude of motor-and somatosensory-evoked potentials were higher in OECs-transplanted rats than in DMEMinjected animals throughout follow-up, whereas the withdrawal response to heat noxious stimulus was lower in OEC-than in DMEM-injected rats. The area of preserved spinal cord was significantly larger in OECs-transplanted rats than in DMEM-injected animals. These results indicate that OECs promote functional and morphological preservation of the spinal cord after photochemical injury. GLIA 42: [275][276][277][278][279][280][281][282][283][284][285][286] 2003.

The goal of this study was to ascertain whether olfactory ensheathing cells (OECs) were able to promote axonal regeneration and functional recovery when transplanted 45 days after complete transection of the thoracic spinal cord in adult rats. OECs promoted partial restitution of supraspinal pathways evaluated by motor evoked potentials and modest recovery of hindlimb movements. In addition, OEC grafts reduced lumbar reflex hyperexcitability from the first month after transplantation. Histological results revealed that OECs facilitated corticospinal and raphespinal axons regrowth through the injury site and into the caudal spinal cord segments. Interestingly, raphespinal but not corticospinal fibers regenerated long distances through the gray matter and reached the lower lumbar segments (L5) of the spinal cord. However, delayed OEC grafts failed to reduce posttraumatic astrogliosis. In conclusion, the beneficial effects found in the present study further support the use of OECs for treating chronic spinal cord injuries.

The mechanisms of injury-induced apoptosis of neurons within the spinal cord are poorly understood. In this study, we show that spinal cord injury (SCI) induces endoplasmic reticulum stress revealed by the activation of an unbalanced unfolded protein response (UPR). Using a weight-drop contusion model of SCI, the UPR activation was characterized by a quick transient phosphorylation of alpha subunit of eukaryotic initiation factor 2 soon restored by the up-regulation of its regulator Gadd34; an effective cleavage/activation of the ATF6a transcription factor leading to up-regulation of the canonical UPR target genes Chop, Xbp1 and Grp78; the presence of the processing of Xbp1 mRNA indicative of inositol requiring kinase 1 activation, and a gradual accumulation of C/EBP homologous transcription factor protein (CHOP) with concomitant caspase-12 activation. Interestingly, the subcellular distribution of CHOP was found in the nucleus of neurons and oligodendrocytes but in the cytoplasm of astrocytes. Considering the pro-apoptotic action attributed to this transcription factor, this phenomenon might account for the different susceptibility of cell types to dye after SCI.

Compelling evidence shows that after root avulsion motoneurons attempt to survive and regenerate before dying. In order to study these mechanisms, unilateral avulsion of L4-L5 spinal roots was performed in adult rats, and the ventral spinal cords were studied from 3 to 28 days post-operation (dpo). Electrophysiological results indicated complete denervation of L4-L5 muscles in the injured limb without functional effects on the contralateral hindlimb. Estimated cell counts showed progressive loss of avulsed motoneurons; at 28 dpo, the number of surviving motoneurons averaged 13% (AE3), 22% (AE0.9), and 29% (AE0.7) in samples stained with cresyl violet, immunostained for choline acetyltransferase (ChAT) and for SMI32, respectively. Regarding glial reactivity, we found an early microglial response, with the highest increase of isolectin B4 (IB4) and Iba1 expression at 3 days, and a slower and progressive response of astrocytes, shown by increasing expression of glial fibrillary acidic protein (GFAP) during the 28 days studied. Accumulation of phosphorylated (RT97þ) and non-phosphorylated (SMI32þ) neurofilaments was observed in the soma of axotomized motoneurons from 3 dpo. RT97 expression was present in approximately 80% (AE3.7) of surviving motoneurons at 7 dpo, and it was related to the regenerative response of motoneurons, as revealed by decreased ChAT expression and co-localization with GAP43. Intense SMI32 immunostaining was observed during the first week after avulsion, appearing in 37% (AE0.9) of surviving motoneurons, but it was not associated with GAP43 expression. Calcitonin gene-related peptide (CGRP) expression in motoneurons was markedly reduced from the second week after avulsion. This study presents a detailed description of motoneuron reaction after root avulsion, which suggests an early time-window during the first 2 weeks for attempts to repair the injury and promote motoneuron survival and regeneration.

The aim of this study was to determine whether a combination of olfactory ensheathing cell (OEC) graft with the administration of FK506, two experimental approaches that have been previously reported to exert protective/regenerative effects after spinal cord injury, promotes synergic restorative effects after complete or partial spinal cord injuries. In partial spinal cord injury, combination of an OEC graft and FK506 reduced functional deficits evaluated by the BBB score, motor-evoked potentials (MEPs) and H reflex tests, diminished cavitation, astrogliosis and increased sparing/regeneration of raphespinal fibers compared to untreated and single-treatment groups of rats. After complete spinal cord transection, the combined treatment significantly improved functional outcomes, promoted axonal regeneration caudal to the lesion, and diminished astrogliosis compared only to non-transplanted animals. Slightly, but nonsignificant, better functional and histological results were found in OEC-grafted animals treated with FK506 than in those given saline after spinal cord transection. Nevertheless, the combined treatment increased the percentage of rats that recovered MEPs and promoted a significant reduction in astrogliosis. In conclusion, this study demonstrates that OEC grafts combined with FK506 promote additive repair of spinal cord injuries to those exerted by single treatments, the effect being more remarkable when the spinal cord is partially lesioned.

The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients. This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged ≥40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4 or who were referred for total knee replacement within 8 years after diagnosis were classified as progressors to severe disease. Clinical variables of the initial stages of the disease (gender, BMI, age at diagnosis, OA in the contralateral knee, and OA in other joints) were registered as potential predictors. Single nucleotide polymorphisms and clinical variables with an association of P < 0.05 were included in the multivariate analysis using forward logistic regression. A total of 23 single nucleotide polymorphisms and the time of prima...

Neurodegenerative processes are preceded by neuronal dysfunction and synaptic disconnection. Disconnection between spinal motoneuron (MN) soma and synaptic target leads either to a retrograde degenerative process or to a regenerative reaction, depending injury proximity among other factors. Distinguished key events associated with one or other processes may give some clues towards new therapeutical approaches based on boosting endogenous neuroprotective mechanisms. Root mechanical traction leads to retrograde MN degeneration, but share common initial molecular mechanisms with a regenerative process triggered by distal axotomy and suture. By 7 days post-injury, key molecular events starts to diverge and sign apart each destiny. We used comparative unbiased proteomics to define these signatures, coupled to a novel network-based analysis to get biological meaning. The procedure implicated the previous generation of combined topological information from manual curated 19 associated biol...