ABSTRACT

We shall first describe the microscopic appearances obtained from a group of histological methods, and then consider the underlying pathological mechanisms.

HISTOLOGICAL FEATURES OF SELECTIVE NEURONAL NECROSIS IN THE ISCHEMIC PENUMBRA Acute Changes-“Classical” Staining Methods

A convenient starting point is to review the conventional (hematoxylin and eosin or cresyl fast violet) histopathology of core and penumbral lesions as recorded after, for example, two hours of experimental, permanent occlusion of the middle cerebral artery (MCAO) in the gyrencephalic brain (cat) (Figs. 1 and 2). In cerebral cortex properly perfusion-fixed under these conditions, Tomlinson (1) was able to distinguish clearly between the appearances of core ischemia and changes in the penumbra. In a core gyrus (identified as such by sustained, terminal depolarization for 15-120 minutes, and exemplified by the ectosylvian gyrus) gross ischemic neuronal damage was present. Neuronal cell bodies were shrunken and usually triangular in shape, and the density of nuclei and cytoplasm was increased; there was cytoplasmic microvacuolation, corresponding to severe mitochondrial swelling, which was observed on electron microscopy. There was widespread and intense perineuronal vacuolation, with “scalloping” of neuronal outlines; the appearances suggested swelling of glial processes adjacent to neurons. On the next peripheral gyrus in the MCA territory, there was patchy or scattered ischemic change. Appearances of individual neurones resembled those observed in the proximal core. The appearances in the outer penumbra gyrus were rarely normal. In most experiments, scalloped neurones with perineuronal vacuolation were seen in two types of distribution: either (i) isolated or in laminar distribution, or (ii) concentrated in foci measuring some 500μm in diameter (Fig. 3). This distribution corresponds closely with that seen in recent studies using ab38 immunocytochemistry (see next section).