Academic literature on the topic 'Neurology; Wallerian degeneration'

During Wallerian degeneration, Schwann cells lose their characteristic of myelinating axons and shift into the state of developmental promyelinating cells. This recharacterized Schwann cell guides newly regrowing axons to their destination and remyelinates reinnervated axons. This Schwann cell dynamics during Wallerian degeneration is associated with oxidative events. Heme oxygenases (HOs) are involved in the oxidative degradation of heme into biliverdin/bilirubin, ferrous iron, and carbon monoxide. Overproduction of ferrous iron by HOs increases reactive oxygen species, which have deleterious effects on living cells. Thus, the key molecule for understanding the exact mechanism of Wallerian degeneration in the peripheral nervous system is likely related to oxidative stress-mediated HOs in Schwann cells. In this study, we demonstrate that demyelinating Schwann cells during Wallerian degeneration highly express HO1, not HO2, and remyelinating Schwann cells during nerve regeneration decrease HO1 activation to levels similar to those in normal myelinating Schwann cells. In addition, HO1 activation during Wallerian degeneration regulates several critical phenotypes of recharacterized repair Schwann cells, such as demyelination, transdedifferentiation, and proliferation. Thus, these results suggest that oxidative stress in Schwann cells after peripheral nerve injury may be regulated by HO1 activation during Wallerian degeneration and oxidative-stress-related HO1 activation in Schwann cells may be helpful to study deeply molecular mechanism of Wallerian degeneration.

✓ Germinomas occurring in the thalamus and basal ganglia sometimes cause atrophy of the cerebral hemisphere on the affected side. The authors present the case of a 12-year-old girl with a germinoma that developed in the basal frontal lobe and cerebral basal ganglia. Magnetic resonance imaging showed atrophy not only of the cerebrum but also of the brainstem. A T2-weighted image revealed an area of high intensity that proved to be wallerian degeneration extending from the corona radiata and internal capsule to the brainstem. The authors suggest that this pathological change may be involved in the development of the symptoms and hemiatrophy associated with germinomas in this region of the brain.

Object. The purpose of this study was to assess how early wallerian degeneration in the corticospinal tracts of patients who had suffered from stroke was detected using three-dimensional anisotropy contrast (3D-AC) magnetic resonance (MR) axonography and to explore the possibility of predicting the prognosis for motor function in these patients. Methods. Ten healthy volunteers and 16 stroke patients with hemiparesis were studied using MR images including 3D-AC MR axonography images obtained using a 1.5-tesla MR imaging system. The axonography was performed using an echoplanar imaging method. All patients underwent MR studies 2, 3, and 10 weeks after stroke onset. To detect wallerian degeneration, the diffusion anisotropy in the corticospinal tracts at the level of the upper pons was evaluated on axial images. These MR findings were compared with the patients' motor functions, which were classified according to the Brunnstrom criteria 12 weeks after the onset of stroke. In all patients with poor recovery (Brunnstrom Stages I–IV), wallerian degeneration, which was demonstrated as a reduction in diffusion anisotropy on axonography images, could be observed in the corticospinal tracts; this degeneration was not found in patients with good recovery (Stages V and VI). Axonography could be used to detect degeneration between 2 and 3 weeks after stroke onset. On conventional T2-weighted MR images, hyperintense areas indicating wallerian degeneration were not detected until 10 weeks after stroke onset. Conclusions. With the aid of 3D-AC MR axonography, wallerian degeneration can be detected in the corticospinal tracts during the early stage of stroke (2–3 weeks after onset), much earlier than it can be detected using T2-weighted MR imaging. The procedure of 3D-AC MR axonography may be useful in predicting motor function prognosis in stroke patients.

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Annually, 150 to 200/1,000,000 people become disabled as a result of brain trauma. Axonal degeneration is a critical, early event following TBI of all severities but whether axon degeneration is a driver of TBI remains unclear. Molecular pathways underlying the pathology of TBI have not been defined and there is no efficacious treatment for TBI. Despite this significant societal impact, surprisingly little is known about the molecular mechanisms that actively drive axon degeneration in any context and particularly following TBI. Although severe brain injury may cause immediate disruption of axons (primary axotomy), it is now recognized that the most frequent form of traumatic axonal injury (TAI) is mediated by a cascade of events that ultimately result in secondary axonal disconnection (secondary axotomy) within hours to days. Proposed mechanisms include immediate post-traumatic cytoskeletal destabilization as a direct result of mechanical breakage of microtubules, as well as catastrophic local calcium dysregulation resulting in microtubule depolymerization, impaired axonal transport, unmitigated accumulation of cargoes, local axonal swelling, and finally disconnection. The portion of the axon that is distal to the axotomy site remains initially morphologically intact. However, it undergoes sudden rapid fragmentation along its full distal length ~72 h after the original axotomy, a process termed Wallerian degeneration. Remarkably, mice mutant for the Wallerian degeneration slow (Wlds) protein exhibit ~tenfold (for 2–3 weeks) suppressed Wallerian degeneration. Yet, pharmacological replication of the Wlds mechanism has proven difficult. Further, no one has studied whether Wlds protects from TAI. Lastly, owing to Wlds presumed gain-of-function and its absence in wild-type animals, direct evidence in support of a putative endogenous axon death signaling pathway is lacking, which is critical to identify original treatment targets and the development of viable therapeutic approaches. Novel insight into the pathophysiology of Wallerian degeneration was gained by the discovery that mutant Drosophila flies lacking dSarm (sterile a/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously recapitulated the Wlds phenotype. The pro-degenerative function of the dSarm gene (and its mouse homolog Sarm1) is widespread in mammals as shown by in vitro protection of superior cervical ganglion, dorsal root ganglion, and cortical neuron axons, as well as remarkable in-vivo long-term survival (>2 weeks) of transected sciatic mouse Sarm1 null axons. Although the molecular mechanism of function remains to be clarified, its discovery provides direct evidence that Sarm1 is the first endogenous gene required for Wallerian degeneration, driving a highly conserved genetic axon death program. The central goals of this thesis were to determine (1) whether post-traumatic axonal integrity is preserved in mice lacking Sarm1, and (2) whether loss of Sarm1 is associated with improved functional outcome after TBI. I show that mice lacking the mouse Toll receptor adaptor Sarm1 gene demonstrate multiple improved TBI-associated phenotypes after injury in a closed-head mild TBI model. Sarm1-/- mice developed fewer beta amyloid precursor protein (βAPP) aggregates in axons of the corpus callosum after TBI as compared to Sarm1+/+ mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phosphorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after TBI. Strikingly, whereas wild type mice exhibited a number of behavioral deficits after TBI, I observed a strong, early preservation of neurological function in Sarm1-/- animals. Finally, using in vivo proton magnetic resonance spectroscopy, I found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1-/- mice compared to controls immediately following TBI. My results indicate that the Sarm1-mediated prodegenerative pathway promotes pathogenesis in TBI and suggest that anti-Sarm1 therapeutics are a viable approach for preserving neurological function after TBI.