α-B-Crystallin as a Tissue Marker of Epileptic Foci in Paediatric Resections

Abstract

Background:We studied α-B-crystallin, a small heat shock chaperone protein upregulated by various "stresses", as an immunocytochemical tissue marker of epileptic foci. Methods: We examined 45 resected brain tissues of epileptic patients, 16 months to 23 years. Postmortem brains of 2 epileptic children and 20 normal fetuses and neonates of 10-41 weeks gestation similarly were studied. Immunocytochemical demonstration of α-B-crystallin was supplemented by neuronal, glial and inflammatory cell markers and electron microscopy (EM) in surgical cases. Autopsy brain tissue of children without epilepsy or neurological disease served as controls. Results: In all resections, α-B-crystallin was overexpressed in astrocytes and oligodendrocytes, including satellite cells adherent to neurons, and occasionally in neurons of neocortex, hippocampus and amygdala. In six cases, reactivity was most intense at or near the epileptic focus, with a diminishing gradient of intensity for 2-3 cm; similar focal expression was seen in autopsy cases. Presence or absence of histological structural lesions was independent of α-B-crystallin expression. Balloon cells and giant atypical cells in tuberous sclerosis were intensely reactive. Reactivity was present in DNETs. No correlation occurred with microglial activation, inflammation or gliosis; no ultrastructural alterations were seen. No expression was seen in fetal brains at any age. Conclusions: Immunoreactive α-B-crystallin is a reliable tissue marker of epileptic foci, regardless of presence or absence of structural lesions; at times it maps the extent of a focus.

A proteomic analysis of pediatric seizure cases associated with astrocytic inclusions

“…However, the presence of the heat shock protein α‐B‐crystallin within hyaline astrocytic inclusions was confirmed. This finding supports the suggestion that α‐B‐crystallin immunoreactivity is a reliable marker of epileptic foci (Sarnat & Flores‐Sarnat, 2009). Nevertheless, the role of filamin A, α‐B‐crystallin, and other proteins previously and presently reported to be immunopositive in the inclusions (Hazrati et al., 2008; Hedley‐Whyte et al., 2009) and their interations with catalase and carbonic anhydrase I, as well as their respective roles in inclusion formation and disease etiology, remain to be elucidated.…”

Immunocytochemical markers of neuronal maturation in human diagnostic neuropathology

“…Others include chronic hypoxic/ischaemic encephalopathy, exposure to x-irradiation or to anti-metabolic and immunosuppressive drugs used as chemotherapy in the treatment of brain tumours, recurrent hypoglycaemia, traumatic brain injury and some primary CNS tumours. Despite the presence of α-B-crystallin being a non-specific response to cellular injury, other conditions can be excluded by medical history and histopathology, so that it can be used as a specific marker for chronic epileptic activity (Sarnat and Flores-Sarnat 2009). The cytoplasmic expression of α-B-crystallin in formalin-fixed paraffin-embedded sections is most intense not only in the glial cells of the white matter just underlying the epileptic cortex but also in the cortical astrocytes and occasionally in the large pyramidal neurons, both in deep layers of the neocortex and in Ammon's horn of the hippocampus.…”

Original article Hemimegalencephaly: foetal tauopathy with mTOR hyperactivation and neuronal lipidosis

“…This association could also explain in part the over-expression of α-B-crystallin in our cases of HME, as this small heat shock protein is very similar to HSP-27, though α-B-crystallin is over-expressed as well at epileptogenic foci in patients without HME [41].…”

“…CD-68 was used as a marker of microglial activation. Alpha-B-crystallin immunoreactivity was used as a tissue marker of epileptic foci (Covance: Emeryville, California, USA; polyclonal LAP-70 carboxy-terminus antibody against peptide of the last 14 amino acids; host: rabbit; 1 : 50 dilution incubated at 37°C) [41]. Bielschowsky silver impregnations were made.…”