Glial Bundles in Spinal Nerve Roots: A Form of Isomorphic Gliosis at the Junction of the Central and Peripheral Nervous System

Abstract

A morphologic study of the spinal nerve roots was undertaken in three cases of Werdnig-Hoffmann disease to investigate the phenomenon of glial bundle formation. The glial elements extended along the ventral roots as discrete cylindrical bundles comprising a large number of parallel astrocytic processes and sparsely scattered cell bodies all enclosed by a basal lamina. The bundles tapered off at a variable distance from the root exit zones. The early stage of glial bundle formation was characterized by the protrusion of astrocytes into the neurilemmal tubes containing degenerated myelinated axons. It was concluded that axonal degeneration, evoking a glial reaction, was the initial event in this process. Subsequently, the reactive astrocytes from the vicinity of the root exit zones enter the neurilemmal tubes previously occupied by myelinated axons and migrated into the domain of the peripheral nervous system in an orderly fashion. Thus glial bundle formation might be considered a special form of isomorphic gliosis occurring in Werdnig-Hoffmann disease and also in several other conditions all sharing a common feature, namely, degeneration of axons within the spinal nerve roots.

Magnetic resonance imaging of the cervical spinal cord in spinal muscular atrophy

“…Although interpreting changes in DTI parameters in terms of pathological, microstructural changes remains challenging, abnormal DTI values could be explained by a range of SMA-associated anatomical and functional changes. Lower AD values may be associated with reduced diffusion in the length of the axon (DeBoy et al, 2007), such as lowered axonal transport in SMA (Fallini et al, 2012; Dale et al, 2011) or it may reflect the axonal degeneration that is found in SMA (Kuru et al, 2009; Ghatak, 1983). Reduced RD may be explained by glial bundles that are frequently described in nerve root pathology in SMA.…”

“…One may expect an increased RD because of axonal degeneration in SMA, leading to increased intracellular space. However, in early post-mortem pathological studies of SMA nerve roots, glial bundles were seen to fill up the spaces of degenerated axons (Ghatak, 1983; Kuru et al, 2009). So, although, located outside of the myelin sheet, one may reason that the glial bundles, still inside the perineurium, will in this way limit the diffusion of water molecules perpendicular to the axon.…”

ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

“…Indeed, neuroinflammatory gliosis was observed in post-mortem CNS samples from SMA patients (Araki et al, 2003; Garcia-Cabezas et al, 2004; Kuru et al, 2009) with the specific occurrence of reactive astrocytic protrusions, termed glial bundles (Ghatak, 1983; Kuru et al, 2009). Astrocytic activation also occurs in the early stages of disease progression in the spinal cord of severe SMA mice (McGivern et al, 2013; Tarabal et al, 2014).…”

“…To date, the few references about an astrocytic phenotype in SMA reveal reactive glial bundles in the CNS of SMA patients (Ghatak, 1983; Kuru et al, 2009) as well as activated astrocytes in severe SMA mice during early symptomatic stages (McGivern et al, 2013; Tarabal et al, 2014). Analysis of primary astrocyte cultures shows that RhoA inactivation is necessary and sufficient to induce stellation (Ramakers and Moolenaar, 1998), an actin-dependent morphology representative of in vivo astrocytes.…”

Inflammation in ALS and SMA: Sorting out the good from the evil

“…Gliosis was also reported to be associated with areas of MN degeneration in the spinal cord and brain stem in all three types of human SMA (Araki et al, 2003; Garcia-Cabezas et al, 2004; Kuru et al, 2009). In addition, in this pediatric paralytic disorder, a singular pathological feature, called glial bundles, can be observed at the level of spinal roots (Chou and Fakadej, 1971; Ghatak, 1983; Kumagai and Hashizume, 1982; Kuru et al, 2009); these glial bundles are thought to correspond to a protrusion of reactive astrocytes into the neurilemmal tubes containing degenerating myelinated axons (Ghatak, 1983). Unlike in the mutant SOD1 model of ALS, gliosis has not been reported in any of the current experimental models of SMA, despite the facts that all, developed a paralytic phenotype and, when symptomatic, exhibit a reduced number of spinal MNs (Kariya et al, 2008; Tsai et al, 2006).…”