Beading of the astrocytic processes (clasmatodendrosis) following head trauma is associated with protein degradation pathways

Abstract

Objectives: To present the incidence of clasmatodendrosis (injured astrocytic processes) and analyse the association between clasmatodendrosis and the ubiquitin proteasome system (UPS) and autophagy lysosome system (autophagy).

Methods: The injured cerebral cortices of 36 autopsy cases were analysed by light microscopy by immunohistochemistry using an anti-glial fibrillary acidic protein (GFAP) antibody and UPS marker antibodies (ubiquitin and lysine 48-linked polyubiquitin chains (K⁴⁸) and autophagy marker (lysine 63-linked polyubiquitin chains (K⁶³), p62/sequestosome 1 and microtubule-associated protein 1 light chain 3 [LC3]). Double-immunofluorescence staining was used to detect the relationships between p62-K⁴⁸, p62-K⁶³ and GFAP-K⁴⁸.

Results: Clasmatodendrosis that was immunoreactive to GFAP or K⁴⁸ was detected by 1 hour up to 14 days following head trauma. The survival time of cases with clasmatodendrosis was significantly shorter than that in cases without clasmatodendrosis (p < 0.01). Involvement of contusion or oedema was significantly frequent in cases with clasmatodendrosis (p < 0.01). There was no significant age difference between cases with clasmatodendrosis and cases without clasmatodendrosis (p = 0.18). Double-immunofluorescence staining for p62-K⁴⁸ and GFAP-K⁴⁸ demonstrated clasmatodendrosis with overlapping fluorescence signals.

Conclusion: Clasmatodendrosis is associated with UPS-mediated, autophagy and relatively acute pathological findings after traumatic intracranial injury.

• Astrocyte
• autophagy
• clasmatodendrosis
• traumatic brain injury
• ubiquitin