ISCHEMIC DAMAGE AND SUBSEQUENT PROLIFERATION OF OLIGODENDROCYTES IN FOCAL CEREBRAL-ISCHEMIA

In order to achieve a better understanding of the pathophysiology of i schemic white matter lesions, oligodendrocytic degeneration and subseq uent proliferation were examined in the mouse model of middle cerebral artery occlusion. In situ hybridization histochemistry for proteolipi d protein messenger RNA was employed as a sensitive and specific marke r of oligodendrocytes, and immunohistochemistry for myelin basic prote in was used as a compact myelin marker. Immunohistochemistry for micro tubule-associated protein 2 and albumin was employed to monitor neuron al degeneration and the breakdown of the blood-brain barrier, respecti vely. In the ischemic core of the caudoputamen, the immunoreactivity f or microtubule-associated protein 2 disappeared and massive albumin ex travasation occurred several hours after vessel occlusion, while prote olipid protein messenger RNA signals remained relatively strong at thi s time. The messenger RNA signals began to attenuate 12 h after ischem ia and were hardly detectable 24 h after ischemica in the whole ischem ic lesion. In situ end-labeling of fragmented DNA showed some cells wi th proteolipid protein messenger RNAs to have DNA fragmentation at thi s period. In contrast to proteolipid protein messenger RNA signals, th e immunoreactivity for myelin basic protein was detected as long as fi ve days after ischemia. An apparent increase in the cells prossessing strong proteolipid protein messenger RNA signals was found five days a fter ischemia, mainly in the corpus callosum and the cortex bordering the infarcted areas. A double simultaneous procedure with in situ hybr idization for proteolipid protein messenger RNA and immunohistochemist ry for glial fibrillary acid protein or lectin histochemistry for macr ophages/microglia showed proliferating oligodendrocytes to be co-local ized with reactive astrocytes and macrophages/microglia. These finding s show that oligodendrocytic damage occurred following ischemic neuron al damage and the breakdown of the blood-brain barrier, but preceded t he breakdown of myelin proteins in the ischemic lesion, that an apopto sis-like process was involved in ischemic oligodendrocytic death, and that surviving oligodendrocytes responded and proliferated in the oute r border of the infarcted area. (C) 1997 IBRO.