Calcium in Neuronal and Glial Response to Axotomy

Neurotrauma assumes an instant or delayed disconnection of axons (axotomy), which affects not only neurons, but surrounding glia as well. Not only mechanically injured glia near the site of disconnection, especially transection, is subjected to the damage, but also glia that is remote from the lesion site. Glial cells, which surround the neuronal body, in turn, support neuron survival, so there is a mutual protection between neuron and glia. Calcium signaling is a central mediator of all post-axotomy events, both in neuron and glia, playing a critical role in their survival/regeneration or death/degeneration. The involvement of calcium in post-axotomy survival of the remote, mechanically intact glia is poorly studied. The purpose of this review is to sum up the calcium-involving mechanisms in responses of neurons and glial cells to axotomy to show their importance and to give some suggestions for future research of remote glia in this context.

Presumed topography of basal ganglion: Derived from TRODAT images in a case of hemorrhagic stroke complicated with asymmetrical cogwheel rigidity

Introduction: Systemic maps of basal ganglion lesion corresponding to clinical symptoms are lacking at present. Only the framework of functional domains in striatum was presumed. We present a case with asymmetrical cogwheel rigidity which is related to the lesion site of the basal ganglion in his functional brain image. Case presentations: A 50-year-old male who suffered from subarachnoid hemorrhage and intracranial hemorrhage presented with upper limbs cogwheel rigidity. The symptom was more severe in the right side than the left side. Dopamine transport images revealed bilateral decreased dopamine transporter binding capacity in bilateral striatum. In left striatum, decreased uptake in dorsal region is more severe than ventral region. Cogwheel rigidity was mildly improved after use of pramipexole. Conclusions: This case report suggests that asymmetrical cogwheel rigidity is linked to the lesion site of the basal ganglion. Topography exists in the striatum and is related to dysfunctional site of parkinsonism. Keywords: cogwheel rigidity; asymmetrical cogwheel rigidity; parkinsonism; basal ganglion; topography

Virtual fractional flow reserve derived from coronary angiography – artery and lesion specific correlations

Introduction Virtual Fractional flow reserve (vFFR) from standard non-hyperaemic invasive coronary angiography (ICA) has emerged as a promising non-invasive test to assess hemodynamic severity of coronary artery disease (CAD). Purpose To investigate the difference in vFFR analysis between vessels and specific lesions. Methods Retrospective analysis of consecutive patients (pts) who underwent invasive functional assessment (iFA) in a tertiary center between 2019 and 2020. vFFR was calculated using dedicated software (CAAS Workstation 8.4) based on coronary angiograms of the acquired in ≥2 different projections, by operators blinded to iFA results. Diagnostic performance of vFFR was evaluated and correlated with iFA, according to coronary vessel, vessel diameter at stenosis, diameter stenosis and area stenosis at lesion. vFFR was considered positive when <0.80. FFR <0.8 and iFR/RFR <0.90 were classified as positive according to current clinical standards. Results 106 coronary arteries of 95 pts (78% male, mean age 67.8±9.7 years) underwent vFFR evaluation. ICA indications were chronic coronary syndrome in 63% or acute coronary syndrome (non-culprit lesion) in the remaining pts. VFFR accuracy was good (AUC 0.839 (p<0.001) and Pearson's correlation coefficient 0.533 (p<0.001) when vFFR was measured in the distal vessel segment. The correlation improved when vFFR were assessed at lesion site (r=0.631, p<0.001) or up to 1cm below the stenosis (0.610, p<0.001). Binary concordance of 89% were observed in RCA and LAD (Sensibility -S 68%, Specificity-Sp 96%, False positive -FP 3.8%, False negative - FN 31%, predictive positive value-PPV 87%, predictive negative value- PNV 89%), while in the circumflex coronary artery binary concordance were of 77% (S 50%; Sp 82%; FP 18%; FN 50%; PPV 33% and PNV 90%). Correlation between vFFR and iFA was higher in vessels ≥2mm (r=0.730, p<0.001). and in lesions in the extremes of the severity spectrum (Table 1). Conclusion vFFR has a moderate to high linear correlation to iFA, depending on the artery and type of lesion studied. The higher correlation was found when vFFR were measured at lesion site, in non-circumflex artery stenosis, in vessels ≥2mm and in vessels with mild or severe stenosis. FUNDunding Acknowledgement Type of funding sources: None.

Murine Susceptibility to Leishmania amazonensis Infection Is Influenced by Arginase-1 and Macrophages at the Lesion Site

Cutaneous leishmaniasis is a zoonotic infectious disease broadly distributed worldwide, causing a range of diseases with clinical outcomes ranging from self-healing infections to chronic disfiguring disease. The effective immune response to this infection is yet to be more comprehensively understood and is fundamental for developing drugs and vaccines. Thus, we used experimental models of susceptibility (BALB/c) and partial resistance (C57BL/6) to Leishmania amazonensis infection to investigate the local profile of mediators involved in the development of cutaneous leishmaniasis. We found worse disease outcome in BALB/c mice than in C57BL/6 mice, with almost 15 times higher parasitic load, ulcerated lesion formation, and higher levels of IL-6 in infected paws. In contrast, C57BL/6 presented higher levels of IFN-γ and superoxide anion (•O2−) after 11 weeks of infection and no lesion ulcerations. A peak of local macrophages appeared after 24 h of infection in both of the studied mice strains, followed by another increase after 240 h, detected only in C57BL/6 mice. Regarding M1 and M2 macrophage phenotype markers [iNOS, MHC-II, CD206, and arginase-1 (Arg-1)], we found a pronounced increase in Arg-1 levels in BALB/c after 11 weeks of infection, whereas C57BL/6 showed an initial predomination of markers from both profiles, followed by an M2 predominance, coinciding with the second peak of macrophage infiltration, 240 h after the infection. Greater deposition of type III collagen and lesion resolution was also observed in C57BL/6 mice. The adoptive transfer of macrophages from C57BL/6 to infected BALB/c at the 11th week showed a reduction in both edema and the number of parasites at the lesion site, in addition to lower levels of Arg-1. Thus, C57BL/6 mice have a more effective response against L. amazonensis, based on a balance between inflammation and tissue repair, while BALB/c mice have an excessive Arg-1 production at late infection. The worst evolution seems to be influenced by recruitment of Arg-1 related macrophages, since the adoptive transfer of macrophages from C57BL/6 mice to BALB/c resulted in better outcomes, with lower levels of Arg-1.

Natural History of Unruptured Vertebral Basilar Artery Dissection: Temporal Changes in Imaging Findings and Contributory Factors

PurposeTo investigate temporal changes in imaging findings of conservatively treated unruptured vertebral basilar artery dissection and its contributing factors.MethodsFifty-three patients who underwent conservative treatment for 64 cases of vertebral basilar artery dissection diagnosed between January 2006 and March 2019 and follow-up of at least 12 months after onset were retrospectively investigated. Statistical analyses of age, sex, medical history, pattern of onset, lesion site, imaging findings and changes over time, regular medication, and outcomes were performed. ResultsChanges in the vascular morphology of the lesion site during the follow-up period were observed in only 23 (43%) patients (median time until change: 19 days). Univariate analysis of factors contributing to morphological changes at the dissection site showed that changes were significantly more likely in younger patients (p = 0.011). Patients taking antiplatelet drugs had a significantly greater rate of deterioration at the dissection site (p = 0.028) than others. On multivariate analysis, age was an independent factor contributing to changes at the dissection site, and taking antiplatelet drugs, particularly clopidogrel, was an independent factor contributing to deterioration. No patient developed intracranial hemorrhage, cerebral infarction, or worsening of neurological symptoms during follow-up.ConclusionsMorphological changes at the dissection site are more likely in younger patients with unruptured vertebral basilar artery dissection and those taking antiplatelet drugs. However, chances of intracranial hemorrhage, cerebral infarction, or worsening of neurological symptoms during conservative therapy are low. Therefore, unruptured vertebral basilar artery dissection may be considered a benign condition.

The Role of Microglia in Modulating Neuroinflammation after Spinal Cord Injury

The pathobiology of traumatic and nontraumatic spinal cord injury (SCI), including degenerative myelopathy, is influenced by neuroinflammation. The neuroinflammatory response is initiated by a multitude of injury signals emanating from necrotic and apoptotic cells at the lesion site, recruiting local and infiltrating immune cells that modulate inflammatory cascades to aid in the protection of the lesion site and encourage regenerative processes. While peripheral immune cells are involved, microglia, the resident immune cells of the central nervous system (CNS), are known to play a central role in modulating this response. Microglia are armed with numerous cell surface receptors that interact with neurons, astrocytes, infiltrating monocytes, and endothelial cells to facilitate a dynamic, multi-faceted injury response. While their origin and essential nature are understood, their mechanisms of action and spatial and temporal profiles warrant extensive additional research. In this review, we describe the role of microglia and the cellular network in SCI, discuss tools for their investigation, outline their spatiotemporal profile, and propose translationally-relevant therapeutic targets to modulate neuroinflammation in the setting of SCI.

Contralateral Axon Sprouting but Not Ipsilateral Regeneration Is Responsible for Spontaneous Locomotor Recovery Post Spinal Cord Hemisection

Spinal cord injury (SCI) usually results in permanent functional impairment and is considered a worldwide medical problem. However, both motor and sensory functions can spontaneously recover to varying extents in humans and animals with incomplete SCI. This study observed a significant spontaneous hindlimb locomotor recovery in Sprague-Dawley rats at four weeks after post-right-side spinal cord hemisection at thoracic 8 (T8). To verify whether the above spontaneous recovery derives from the ipsilateral axonal or neuronal regeneration to reconnect the lesion site, we resected either the scar tissue or right side T7 spinal cord at five weeks post-T8 hemisected injury. The results showed that the spontaneously achieved right hindlimb locomotor function had little change after resection. Furthermore, when T7 left hemisection was performed five weeks after the initial injury, the spontaneously achieved right hindlimb locomotor function was dramatically abolished. A similar result could also be observed when T7 transection was performed after the initial hemisection. The results indicated that it might be the contralateral axonal remolding rather than the ipsilateral axonal or neuronal regeneration beyond the lesion site responsible for the spontaneous hindlimb locomotor recovery. The immunostaining analyses and corticospinal tracts (CSTs) tracing results confirmed this hypothesis. We detected no substantial neuronal and CST regeneration throughout the lesion site; however, significantly more CST fibers were observed to sprout from the contralateral side at the lumbar 4 (L4) spinal cord in the hemisection model rats than in intact ones. In conclusion, this study verified that contralateral CST sprouting, but not ipsilateral CST or neuronal regeneration, is primarily responsible for the spontaneous locomotor recovery in hemisection SCI rats.

Panniculitis in Children

Panniculitides form a heterogenous group of inflammatory diseases that involve the subcutaneous adipose tissue. These disorders are rare in children and have many aetiologies. As in adults, the panniculitis can be the primary process in a systemic disorder or a secondary process that results from infection, trauma or exposure to medication. Some types of panniculitis are seen more commonly or exclusively in children, and several new entities have been described in recent years. Most types of panniculitis have the same clinical presentation (regardless of the aetiology), with tender, erythematous subcutaneous nodules. Although the patient’s age and the lesion site provide information, a histopathological assessment is sometimes required for a definitive diagnosis and classification of the disorder. In children, most panniculitides are lobular. At present, autoimmune inflammatory diseases and primary immunodeficiencies have been better characterised; panniculitis can be the presenting symptom in some of these settings. Unexplained panniculitis in a young child should prompt a detailed screen for monogenic immune disorders because the latter usually manifest themselves early in life. Here, we review forms of panniculitis that occur primarily in children, with a focus on newly described entities.