Lack of adenylate cyclase 1 (AC1): consequences on corticospinal tract development and on locomotor recovery after spinal cord injury.

Cyclic AMP (cAMP) signalling pathways are involved in axonal growth and regeneration. The calcium-calmodulin- stimulated adenylate cyclase 1 (AC1), a regulator of cAMP levels, is strongly expressed in the corticospinal motor neurons (CSMN) in cerebral cortex layer V during development, but its role in the development of the corticospinal tract (CST) is unknown. Here, we analyse the organization of the CST pathway using anterograde and retrograde tracers in the barrelless (brl) mouse that carries an inactivating mutation of the AC1 gene. We show that in brl mice the general organization of the CST is normal but there is an increase in the number of axons in the ipsilateral contingent in the dorsal and ventral medial funiculi of the cervical spinal cord. The density of CSMN in layer V of the motor cortex is increased in brl compared to wild-type mice. Thus, lack of AC1 likely perturbs late phases of CSMN and CST development. Next, we examine the motor recovery after a spinal cord injury (SCI). We find that brl mice show enhanced locomotor functions as assessed by the BMS (Basso mouse scale) as early as 6h and up to 6 weeks after SCI, indicating a smaller responsiveness of brl mice to SCI. It is therefore possible that developmental effects on motor systems might decrease the locomotor effects consecutive to a SCI. This point is particularly important with regards to the use of transgenic animals for testing SCI recovery.

[Levator ani trauma after childbirth, from stretch injury to avulsion: review of the literature]. / Traumatismes du levator ani après l'accouchement, de l'étirement à l'avulsion : revue de la littérature.

OBJECTIVE: Pelvic floor injuries as avulsion (disruption of the muscle) or overdistension were identified in 15 to 35% of deliveries. Our objective is to clarify the consequences of these muscles trauma on pelvic floor symptoms, pelvic organ prolapse and the management of postnatal assessment of pelvic floor function. METHOD: The literature search was conducted over a period from 2000 to January 2013 using the PubMed database and the following keywords: levator ani, ultrasound, magnetic resonance imaging, pelvic floor, obstetric trauma, pelvic organ prolapse, incontinence, delivery, avulsion. Seventy-four articles were identified, 43 were selected. The level of evidence was determined using the Oxford table. RESULTS: The instrumental extraction was found as the main risk factor with a prevalence of avulsions from 35% (NP3) to 72% (NP3) and an odd-ratio of 3.4 (NP3). Whatever the mode of assessment, the strength of the pelvic floor was reduced in 100% of cases of avulsion. Avulsions were diagnosed clinically and could be confirmed by ultrasound or MRI (correlation palpation imaging/k=0.497 (NP2) to 86% (NP3). An association was found with the risk of genital prolapse (odd-ratio from 2 [NP4] to 7 for prolapse grade 1 [NP4]) and fecal incontinence (16% [NP3] to 72% [NP4] with an odd-ratio of 14 [NP4]). CONCLUSION: This review has shown that obstetric muscle avulsions had an impact on pelvic organ prolapse and anal continence. The mode of the pelvic floor muscle postnatal assessment remains to be defined.

Klf9 is necessary and sufficient for Purkinje cell survival in organotypic culture.

During their phase of developmental programmed cell death (PCD), neurons depend on target-released trophic factors for survival. After this period, however, they critically change as their survival becomes target-independent. The molecular mechanisms underlying this major transition remain poorly understood. Here, we investigated, which transcription factors (TFs) might be responsible for the closure of PCD. We used Purkinje cells as a model since their PCD is restricted to the first postnatal week in the mouse cerebellum. Transcriptome analysis of Purkinje cells during or after PCD allowed the identification of Krüppel like factor 9 (Klf9) as a candidate for PCD closure, given its high increase of expression at the end of the 1st postnatal week. Klf9 function was tested in organotypic cultures, through lentiviral vector-mediated manipulation of Klf9 expression. In absence of trophic factors, the Purkinje cell survival rate is of 40%. Overexpression of Klf9 during PCD dramatically increases the Purkinje cell survival rate from 40% to 88%, whereas its down-regulation decreases it to 14%. Accordingly, in organotypic cultures of Klf9 knockout animals, Purkinje cell survival rate is reduced by half as compared to wild-type mice. Furthermore, the absence of Klf9 could be rescued by Purkinje cell trophic factors, Insulin growth factor-1 and Neurotrophin3. Altogether, our results ascribe a clear role of Klf9 in Purkinje cell survival. Thus, we propose that Klf9 might be a key molecule involved in turning off the phase of Purkinje PCD.

Cell death and axon regeneration of Purkinje cells after axotomy: challenges of classical hypotheses of axon regeneration.

Although adult mammalian neurons are able to regenerate their axons in the peripheral nervous system under certain conditions, they are not able to do it in the central nervous system. The environment surrounding the severed axons appears to be a key factor for axon regeneration. Many studies aiming to enhance axon regeneration in the CNS of adult mammals have successfully manipulated this environment by adding growth permissive molecules and/or neutralizing growth inhibitory molecules. In both cases, the number of axons able to regenerate was low and the different neuronal populations were not equal in their regenerative response, suggesting that manipulation of the environment is not always sufficient. This is particularly well illustrated in the cerebellar system, in which axotomized inferior olivary neurons regenerate when confronted with a permissive environment, whereas mature Purkinje cells do not. The intrinsic ability of a neuron to regenerate its axon is generally correlated with the intensity of its reaction to axotomy (expression of molecules, probability to die). Furthermore, molecules such as GAP-43 (growth-associated molecule) and c-Jun are involved in both axon regeneration and cell death suggesting that these two processes are linked. Surprisingly, Purkinje cells lose their capacity to regenerate their axon (even in the absence of myelin) during development before losing their capacity to react to an axotomy by cell death. These results emphasize the different reactions to axotomy between neuron types and underline that in Purkinje cells, the two cell decisions (axon regeneration and cell death) are differently regulated and therefore not part of the same signaling pathway.

Late axonal sprouting of injured Purkinje cells and its temporal correlation with permissive changes in the glial scar.

Purkinje cells can survive axotomy for as long as 18 months without retracting their severed axons. During this period of time, the fate of the terminal bulbs of axotomized Purkinje cell axons and their relationship with the glial scar were determined. Terminal axonal sprouting begins three months after the lesion and continuously increases up to 18 months (the longest survival time studied), when the sprouts establish synaptic contacts, mainly on granule cell dendrites at the glomeruli. Cellular changes in the glial scar were analyzed to determine whether the late onset and continuous increase of axonal sprouting could be correlated with an increase of permissive factors and/or a decrease of inhibitory factors for axonal growth. Activated macrophages disappeared much earlier than did the initiation of sprouting. Myelin and its associated neurite growth inhibitory molecules began to decrease from three months after the lesion. This decrease was uneven and not correlated spatially with the sprouting. Reactive astrogliosis was heterogeneous: only some of the reactive astrocytes expressed PSA-NCAM, the embryonic form of the neural cell adhesion molecule, a permissive substratum for neurite outgrowth. The expression of PSA-NCAM occurred concurrently with sprouting in the area of gliosis containing Purkinje cell sprouts. Moreover, the ultrastructural study showed that the majority of sprouts (75%) were totally ensheathed by astrocytic processes. Thus, long-term glial scars are permissive to axonal sprouting, suggesting that reactive astrocytes, either through the expression of permissive molecules or by preventing direct contact between axonal elements and myelin inhibitory molecules, regulate the sprouting.

Parasagittal compartmentation of adult rat Purkinje cells expressing the low-affinity nerve growth factor receptor: changes of pattern expression after a traumatic lesion.

The pattern of expression of p75, the low affinity nerve growth factor receptor, in the adult rat cerebellum and its fate after a traumatic lesion were analysed using immunohistochemical localization of this receptor. A subset of Purkinje cells was immunoreactive for low affinity nerve growth factor receptor in the intact adult cerebellum. These cells were arranged in alternating positive and negative parasagittal compartments along the cerebellar cortex. This pattern of expression had 90% homology with zebrin I. After a traumatic lesion, the specific pattern of expression of zebrin I remained unchanged, whereas the low affinity nerve growth factor receptor pattern changed as early as one day: Purkinje cells near the lesion site, independent of zebrin I staining, became immunoreactive. During the first week, the increase in immunoreactivity remained high. Thereafter, there was a short, fast decrease followed by a long period in which a faint immunostaining on lesioned Purkinje cells is maintained for up to one year. The increase in the expression of the low affinity nerve growth factor receptor by all traumatically affected Purkinje cells suggests a correlation between this specific up-regulation and the high resistance of these neurons to axotomy or other traumatic injuries.

[Non surgical reduction of false aneurysms of the femoral artery with echo-Doppler control]. / Réduction non chirurgicale de faux anévrismes de l'artère fémorale sous contrôle écho-doppler.

The authors report four cases of repair of femoral pseudoaneurysms under pulsed (1 case) and colour Doppler (3 cases) guidance, performed between January and October 1992 and compare the results with previously published reports of this new technique. They obtained 3 complete successes without complications and 1 failure with complications and a contraindication to the method. A review of the literature and the personal experience of the authors are described. This effective and usually complication-free technique should be proposed as an alternative to surgery. It should be undertaken as early as possible and remains a long and fastidious procedure poorly adapted to present nomenclature of medical procedures. It should be systematically proposed in cases of pseudo-aneurysms complicating the implantation of endoarterial prostheses.

[Diagnostic value of the combination of echography-plethysmography in deep venous thromboses of the legs]. / Valeur diagnostique de l'association échographie-pléthysmographie dans les thromboses veineuses profondes des membres inférieurs.

The association of two non invasive methods: real time ultrasonography and plethysmography was studied prospectively for the diagnosis of deep vein thrombosis (DVT) in 70 patients. Their results were compared to contrast venography considered to the reference procedure. Venography showed DVT in 32 patients. Ultrasonography had a sensitivity of 69% and a specificity of 98%. The false negative results were related to iliac or calf vein thrombosis. Plethysmography had lower results than US (Se = 57%, Sp = 90%). In this study the sensivity of the two methods, either isolated or associated was not sufficient to allow their substitution to venography. Their association in all cases did not give better results than US alone. Because of its high specificity US can be performed first in cases of suspicion of DVT, especially in high risk patients. Plethysmography seems not to be necessary for the diagnosis.