Astrocytic Demise in the Developing Rat and Human Brain after Hypoxic-Ischemic Damage

Abstract

In order to approach the physiopathological mechanism underlying the selective susceptibility of the immature brain to hypoxia-ischemia (HI), we have compared the lesions experimentally induced in postnatal day 7 rats using a model of neonatal stroke with those occurring in human fetal and neonatal brains. We first observed that gray and white matter lesions demonstrated a similar organization (core with cell loss and/or cavity and penumbra) and evolutionary pattern between experimental and human HI lesions. We then observed that, in the intermediate white matter, GFAP- and vimentin-positive astrocytes exhibited clasmatodendrosis and represent a major cell population involved in cell death in human brains (56.3 and 67.9%, respectively). In rat brains, GFAP- and TUNEL-positive astrocytes were also highly vulnerable, increasing between 6 (31%) and 72 (58%) hours after ischemia. Together, these results indicate that astroglial dysfunction may play a critical role in determining the progress and outcome of acute hypoxic-ischemic injury particularly in the developing brain.

Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica

“…Clasmatodendrosis was initially described in the beginning of the 20th century, as a regressive morphological change of astrocytes with cytoplasmic swelling and vacuolation with beading and dissolution of their dendritic processes [16]. Recently, clasmatodendrosis has been recognized to be associated with various diseases such as vascular diseases including Binswanger’s leukoencephalopathy [10, 52] or epilepsy [19]. It appears to reflect a regressive change of astrocytes, which can be induced by several mechanisms, such as for instance energy deficiency [16, 19] or autophagic cell death [45], and which may finally result in astrocyte apoptosis [19].…”

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

“…Clasmatodendrosis was previously detected by several antibodies in brain tissues after nontraumatic brain injury, including the anti-GFAP, anti-IgG, anti-IgM, anti-fibrinogen, anti-C1, anti-C3d, anti-vimentin, anti-alpha-B crystallin, anti-apolipoprotein-E and antilaminin antibodies [2,24]. In the present study, clasmatodendrosis that was immunoreactive to anti-GFAP and anti-K 48 antibodies was observed by light microscopy and clasmatodendrosis was also identified by double-immunofluorescence staining for p62, K 48 and K 63 .…”

Autophagy and Apoptosis Are Differentially Induced in Neurons and Astrocytes Treated with an In Vitro Mimic of the Ischemic Penumbra

“…Together, these results indicate that astrocytes are more sensitive to ischemic and metabolic stresses than neurons. Other groups have also reported that astrocytes are more susceptible to metabolic or ischemic injury than neurons; and this heightened sensitivity to metabolic stress may contribute significantly to penumbral expansion since astroglial dysfunction plays a key role in the progression of ischemic injuries in vivo and because there is evidence that astrocytic demise precedes and directly contributes to neuronal demise in ischemia [58], [59].…”