The phenomenon of clasmatodendrosis

Abstract

Clasmatodendrosis derives from the Greek for fragment (klasma), tree (dendron), and condition (-osis). Cajal first used the term in 1913: he observed disintegration of the distal cell processes of astrocytes, along with a fragmentation or beading of proximal processes closer to the astrocyte cell body. In contemporary clinical and experimental reports, clasmatodendrosis has been observed in models of cerebral ischemia and seizures (including status epilepticus), in elderly brains, in white matter disease, in hippocampal models and cell cultures associated with amyloid plaques, in head trauma, toxic exposures, demyelinating diseases, encephalitides and infection-associated encephalopathies, and in the treatment of cancer using immune effector cells. We examine evidence to support a claim that clasmatodendrotic astrocyte cell processes overtly bead (truncate) as a morphological sign of ongoing damage premortem. In grey and white matter and often in relationship to vascular lumina, beading becomes apparent with immunohistochemical staining of glial fibrillary acidic protein when specimens are examined at reasonably high magnification, but demonstration of distal astrocytic loss of processes may require additional marker study and imaging. Proposed mechanisms for clasmatodendrotic change have examined hypoxic-ischemic, osmotic-demyelinating, and autophagic models. In these models as well as in neuropathological reports, parenchymal swelling, vessel-wall leakage, or disturbed clearance of toxins can occur in association with clasmatodendrosis. Clasmatodendrotic features may serve as a marker for gliovascular dysregulation either acutely or chronically. We review correlative evidence for blood-brain barrier (BBB) dysfunction associated with astrocytic structural change, with attention to interactions between endothelial cells, pericytes, and astrocytic endfeet.

Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease

“…In amyotrophic lateral sclerosis (ALS), astrocytes atrophy followed by increased cell death can interfere with glutamate uptake causing silencing and degeneration of motor neuronal activity (Rossi et al, 2008), whereas in AD, it has been linked with early synaptic loss and cognitive impairment (Verkhratsky et al, 2010, 2015). Clasmatodendrosis, which is a form of astrodegeneration characterised by extreme terminal disintegration, fragmentation, or beading of the distal cell processes, has been also observed in postmortem neuropathological specimen of seizures, cerebral ischaemia as well as in elderly/ageing brain (Balaban et al, 2021). At the same time, the pathological remodelling of astrocytes results in the possession of toxic characteristics/functions which promote the pathophysiology of the disease.…”

“…Clasmatodendrosis, which is a form of astrodegeneration characterised by extreme terminal disintegration, fragmentation, or beading of the distal cell processes, has been also observed in postmortem neuropathological specimen of seizures, cerebral ischaemia as well as in elderly/ageing brain (Balaban et al, 2021). At the same time, the pathological remodelling of astrocytes results in the possession of toxic characteristics/functions which promote the pathophysiology of the disease.…”

Motor neuron pathology in CANVAS due to RFC1 expansions

“…The presence of protoplasmic astrocytes in contact with the cell body of motor neurons, the fragmented aspect of astrocytic processes particularly visible in the molecular layer of the cerebellum, the close contact of astrocytic extensions with the dendrites of motor neurons and Purkinje cells suggest clasmatodendrosis described by Cajal. 27 Although this type of anomaly should be interpreted with caution 28 and requires further investigations, it has recently been proposed that impair synaptic transmission by contact with dendritic spines 29 could offer a plausible explanation for the severity of the neurological disease contrasting with the absence of significant lesions, except those related to Parkinson's disease.…”

Calpain-mediated proteolysis of vimentin filaments is augmented in giant axonal neuropathy fibroblasts exposed to hypotonic stress

“…This will be tested in future work, particularly in the context of GAN disease-relevant cell types harboring abnormal IF aggregates, specifically neurons and astrocytes. In many pathological states, including neurodegeneration and traumatic brain injury, astrocytes may undergo a response, known as “clasmatodendrosis”, morphologically reflected in IF network breakdown of their cytoskeletal proteins, including GFAP and vimentin ( Balaban et al, 2021 ). Clasmatodendrosis (from Greek klasma , fragment, + dendron , tree, + osis, condition), is characterized by prominent swelling of the astrocyte cell body, together with pronounced beading and fragmentation of astrocyte cytoplasmic processes, readily visualized by GFAP and vimentin staining ( Tomimoto et al, 1997 ; Early et al, 2020 ).…”