title: Mannitol infusion immediately after reperfusion suppresses the development of focal cortical infarction after temporary cerebral ischemia in gerbils.
abstract: Previously we found that, after temporary cerebral ischemia, microvasculogenic secondary focal cerebral cortical ischemia occurred, caused by microvascular obstruction due to compression by swollen astrocytic end-feet, resulting in focal infarction. Herein, we examined whether mannitol infusion immediately after restoration of blood flow could protect the cerebral cortex against the development of such an infarction. If so, the infusion of mannitol might improve the results of vascular reperfusion therapy. We selected stroke-positive animals during the first 10 min after left carotid occlusion performed twice with a 5-h interval, and allocated them into four groups: sham-operated control, no-treatment, mannitol-infusion, and saline-infusion groups. Light- and electron-microscopic studies were performed on cerebral cortices of coronal sections prepared at the chiasmatic level, where the focal infarction develops abruptly in the area where disseminated selective neuronal necrosis is maturing. Measurements were performed to determine the following: (A) infarct size in HE-stained specimens from all groups at 72 and 120 h after return of blood flow; (B) number of carbon-black-suspension-perfused microvessels in the control and at 0.5, 3, 5, 8, 12 and 24 h in the no-treatment and mannitol-infusion groups; (C) area of astrocytic end-feet; and (D) number of mitochondria in the astrocytic end-feet in electron microscopic pictures taken at 5 h. The average decimal fraction area ratio of infarct size in the mannitol group was significantly reduced at 72 and 120 h, associated with an increased decimal fraction number ratio of carbon-black-suspension-perfused microvessels at 3, 5 and 8 h, and a marked reduction in the size of the end-feet at 5 h. Mannitol infusion performed immediately after restitution of blood flow following temporary cerebral ischemia remarkably reduced the size of the cerebral cortical focal infarction by decreasing the swelling of the end-feet, thus preventing the microvascular compression and stasis and thereby microvasculogenic secondary focal cerebral ischemia.
authors.affiliation: Laboratory for Neurodegenerative Pathology, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science; Division of Neuropathology, Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Umeo
authors.initials: U
authors.lastname: Ito
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hakamata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Watabe
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Oyanagi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D020520:Brain Infarction / Q000188:drug therapy* / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D005849:Gerbillinae; D007262:Infusions, Intravenous; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000627:therapeutic use*; D055806:Microvessels / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015424:Reperfusion
chemical_list: D018696:Neuroprotective Agents; D008353:Mannitol
keywords: astrocytic end-feet; mannitol infusion immediately after reperfusion; microvasculogenic secondary focal cerebral ischemia; suppression of focal infarction; temporary cerebral ischemia