Apoptosis and necrosis in the newborn piglet brain following transient cerebral hypoxia-ischaemia

Abstract

We have used a porcine model of global hypoxia-ischaemia to examine the mode and extent of cell damage to the newborn brain. Apoptosis and necrosis were observed in neurons and glial cells following transient cerebral hypoxic-ischaemic injury (HII) by haematoxylin and eosin staining and by in situ end labelling (ISEL). Quantitative neuropathological analysis of the cingulate gyrus, the hippocampus and the cerebellum showed that the degree of both apoptosis and necrosis increased with the severity of injury in these brain areas. The hippocampus and cerebellar cortex were particularly sensitive to HII. Furthermore, some cell types were more susceptible to a particular mode of cell death. In the cerebellum. Purkinje cells died by necrosis but never by apoptosis. In contrast, cerebellar granule cells were frequently apoptotic, but never necrotic. In the hippocampus, apoptosis occurred in the inner layer neurons of the dentate fascia and necrosis in the more mature outer layer neurons. This suggests that immature neurons may be more prone to apoptotic death while terminally differentiated neurons die by necrosis. Apoptosis but not necrosis was seen in cerebral white matter. This model may help to elucidate the factors that determine cell fate following HII and aid the development of cerebroprotective strategies.

Cerebellar anomalies in congenital murine toxoplasmosis

“…In the present study, the latter phenomenon is well-illustrated by the shrunken cell bodies, pyknotic nuclei, and the cytoplasmic eosinophilia of affected PCs as well as the necrosis of numerous centrilobular granule cells. Hypoxia-ischemia is the most likely cause of cell death and the cerebellar cells known to be most vulnerable to hypoxia are the PCs and granule cells (Yue et al 1997).…”

The Cannabinoid WIN 55212-2 Mitigates Apoptosis and Mitochondrial Dysfunction After Hypoxia Ischemia

“…Because it is well known that apoptosis accounts for neuronal death after hypoxia-ischemia [32,39,[79][80][81][82][83], the decrease in this cell death mechanism is likely to mitigate the progression of the brain lesion. These findings, summed up in previously described neuroprotective properties of cannabinoids, support the high interest in cannabinoids as a future feasible strategy to be included in neonatal hypoxicischemic encephalopathy management.…”

Hypoxic changes in Purkinje cells of the human cerebellum

“…To investigate the significance of the above-mentioned cytological criteria of cell necrosis for the diagnosis and timing of hypoxicinduced brain lesions, the various cell-types (PC I-III) were counted in samples from the cerebellar cortex of individuals with a history of acute or prolonged cerebral hypoxia/ ischemia before death. As Purkinje cells failed to display spherical/ovoid cytoplasmic/nuclear fragments, referred to as apoptotic bodies, or TUNEL-positive staining [25], apoptotic cell death was not investigated in this study.…”