Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

Background: Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 ( a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.Results: Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.Conclusion: Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

<p>Abstract</p> <p>Background</p> <p>The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve.</p> <p>Results</p> <p>We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST) axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC) axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion), most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice.</p> <p>Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG) cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses revealed significant differences between wild-type and knockout mice.</p> <p>Conclusion</p> <p>These findings show that NG2 is unlikely to be a major inhibitor of axonal regeneration after injury to the CNS, and, further, that NG2 is unlikely to be necessary for regeneration or functional recovery following peripheral nerve injury.</p

Assessment of corrosion in retrieved spine implants

Recently the use of dissimilar metals in spine instrumentation has increased, especially in the case of adult deformities, where rods made from Cobalt Chrome alloys (CoCr) are used with Titanium (Ti) screws. The use of dissimilar metals increases the risk of galvanic corrosion and patients have required revision spine surgery due to severe metallosis that may have been caused by corrosion. We aimed to assess the presence of corrosion in spine implant retrievals from constructs with two types of material combinations: similar (Ti/Ti) and dissimilar (CoCr/Ti). First, we devised a grading score for corrosion of the rod-fixture junctions. Then, we applied this score to a collection of retrieved spine implants. Our proposed corrosion grading score was proven reliable (kappa > 0.7). We found no significant difference in the scores between 4 CoCr and 11 Ti rods (p = 0.0642). There was no indication that time of implantation had an effect on the corrosion score (p = 0.9361). We recommend surgeons avoid using implants designs with dissimilar metals to reduce the risk of corrosion whilst a larger scale study of retrieved spine implants is conducted. Future studies can now use our scoring system for spine implant corrosion

The Relative Merits of Posterior Surgical Treatments for Multi-Level Degenerative Cervical Myelopathy Remain Uncertain: Findings from a Systematic Review.

OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments

Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

<p>Abstract</p> <p>Background</p> <p>Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.</p> <p>Results</p> <p>Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.</p> <p>Conclusion</p> <p>Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.</p

Cushing's disease in children and adolescents: 20 years of experience in a single neurosurgical center.

OBJECTIVE: This is a retrospective analysis of 25 consecutive pediatric patients with Cushing's disease who underwent transsphenoidal surgery performed by a single neurosurgeon in a specialist center during a 20-year period. This article discusses the presentation of Cushing's disease, the endocrinological investigation with particular reference to bilateral inferior petrosal sinus sampling (BIPSS), the operative management with reference to specific pediatric difficulties of the transsphenoidal approach and the use of intraoperative image guidance, and the analysis of these cases as regards postoperative complications and outcomes of this rare condition in young patients. METHODS: All patients underwent detailed endocrine investigation and imaging in the form of computed tomography and/or magnetic resonance imaging. BIPSS was performed in 19 patients (76%), with successful lateralization of the side of the microadenoma in 14 (74%) and prediction of a central tumor in four (94% total prediction rate). Surgical removal was via the sublabial, paraseptal, transsphenoidal route. RESULTS: There were 15 male and 10 female patients, with a mean age of 13.4 years (range, 6.6-17.8 yr). Weight gain was the most common presentation (100%), and then growth impairment (96%), fatigue and skin changes (64%), and hypertension (32%). Postoperative complications included growth hormone deficiency (36%), transient diabetes insipidus (12%), panhypopituitarism (4%), and transient cerebrospinal fluid rhinorrhea (4%). The median follow-up period was 59.5 months (range, 6-126 mo). Overall, 15 patients (60%) achieved surgical cure or remission, of which 14 outcomes were obtained using the results of BIPSS. Ten patients (40%) required postoperative radiotherapy to achieve "remission." There were no cases of meningitis, no neurological deficits, no reoperations, and no mortality. CONCLUSION: Cushing's disease in children and adolescents is a rare illness. The accurate preoperative localization of the adenoma is essential for achieving good results. In this series, BIPSS was far more accurate in localizing the adenoma than computed tomography or magnetic resonance imaging. Imaging, however, is useful for the exclusion of other intracranial problems. Transsphenoidal surgery was safe and efficacious in achieving cure in the majority of cases. The challenge of transsphenoidal surgery in this age group is the small pituitary fossa and the absence of sphenoid sinus aeration in some cases. We found the use of intraoperative neuronavigation to be an excellent aid in overcoming such anatomic difficulties

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse-1

<p><b>Copyright information:</b></p><p>Taken from "Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse"</p><p>http://www.biomedcentral.com/1471-2202/8/80</p><p>BMC Neuroscience 2007;8():80-80.</p><p>Published online 27 Sep 2007</p><p>PMCID:PMC2100060.</p><p></p>h anti-NG2 antibody. Arrowheads delineate the edges of the tail snip sections. Strong NG2 immunofluorescence is apparent in hair follicles (h), sebaceous glands (s) and bone marrow (bm) and other structures in Fig. 1a but no NG2 fluorescence is detectable in Fig. 1b. Bar = 200 μm and also applies to Fig. 1b

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse-0

<p><b>Copyright information:</b></p><p>Taken from "Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse"</p><p>http://www.biomedcentral.com/1471-2202/8/80</p><p>BMC Neuroscience 2007;8():80-80.</p><p>Published online 27 Sep 2007</p><p>PMCID:PMC2100060.</p><p></p>h anti-NG2 antibody. Arrowheads delineate the edges of the tail snip sections. Strong NG2 immunofluorescence is apparent in hair follicles (h), sebaceous glands (s) and bone marrow (bm) and other structures in Fig. 1a but no NG2 fluorescence is detectable in Fig. 1b. Bar = 200 μm and also applies to Fig. 1b