Diabetes Mellitus Causes Early Ultrastructural Changes to the Nuclei and Mitochondria of Neurons and Astrocytes in Rats Subjected to a Brief Period of Cerebral Ischemia

It has been previously demonstrated that hyperglycemia caused by glucose infusion or diabetes enhances neuronal damage induced by transient global or focal cerebral ischemia [1].In addition to neurons, astrocytes may also be the target and damage to the astrocytes may in turn influence the neuronal survival [2].The objective of the present study was to define the ultrastructural alterations of neurons and astrocytes in streptozotocin-induced diabetic rats subjected to a brief period of global ischemia.Five minutes of global ischemia was induced in non-diabetic and diabetic rats.Brain samples were collected after 30 min, 6 h, 1, 3, and 7 days of recirculation as well as from sham-operated controls.Electron microscopy demonstrated homogenous neuronal nuclear chromatin, visible nuclei and intact nuclear membranes up to 1 d of recovery in both non-diabetic and diabetic rats.Mitochondrial morphology was normal up to 6 h of recovery, but disarray of mitochondrial cristae, mild lucency and swelling were observed in a few mitochondria after 1 d of recovery in non-diabetics.In contrast, diabetic rats showed disarray of mitochondrial cristae after 30 min and developed more severe swelling after 6 h and 1d of recovery.These findings are consistent with our previous published ultrastructural studies in rats subjected to an intermediate period of global ischemia [3].No apoptotic bodies were observed in any of the sections examined.In astrocytes, the nuclear chromatin was homogenous, nuclei were visible, and nuclear membrane was intact up to 1 d of recovery in cortex.Mitochondrial morphology was normal up to 1 d of recovery in nondiabetic rats.Compare to nondiabetic rats, nuclear and mitochondrial morphological alterations were prominent in diabetic rats after 1 day of recovery.Nuclear shrinkage, chromatin condensation and void space were evident.Disarray of mitochondrial cristae, lucency, and swelling were observed in astrocytes after 1 d of recovery.The results suggest that diabetic hyperglycemia causes damage to both neurons and astrocytes in early reperfusion phase.The damage to mitochondria in neurons and astrocytes may activate mitochondria-initiated cell death pathways results in DNA fragmentation and ischemic cell death.