The role of cell adhesion molecules of inflammatory cell & brain endothe-lial cell in post brain ischemic/hypoxic hypoperfusion

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 08407051
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: NIIGATA UNIVERSITY
• Principal Investigator: FUKUDA Satoru Niigata University, Department of Anesthesiology, Associate Professor, 医学部, 助教授 (30116751)
• Co-Investigator(Kenkyū-buntansha): TAGA Kiichiro Niigata Univ.Med.Hosp Lecturer, 医学部附属病院, 講師 (00163329)
• Project Period (FY): 1996 – 1998
• Keywords: Cell adhesion molecule / Brain ischemia / Brain Hypoxia / Reoxygenation / Hypoperfusion / Anesthetics / Isoflurane / Ketamine

Research Abstract

Post reperfusion/reoxygenation brain hypoperfusion is a serious problem in conditions such as cardiac arrest, shock, brain trauma and cerebral infarction. We investigated the influence of cell adhesion molecules (CADM) of polymorphonuclear leukocyte (PMNL) and brain endothelial cells on post reoxygenation brain hypoperfusion during anesthesia. In vitro experiments, we investigated the effects of ketamine and thiopental on the expression of cell adhesion molecules of human unstimulated, fMLP- and PMA-stimulated PMNLs. From this experiment we found clinical concentration of thiopental, which has been reported to protect focal brain ischemia, attenuated the increase of CD11b on PMNLs, but not that of CD62L.In vitro experiment it is difficult to the effect of inhalation anesthetics on the CADM.Therefore, we investigated the influence of isoflurane (0.5 - 1.5 MAC) on the CADM expression after hypoxia (5% O_2, 10 min) -reoxygenation (120 mm) in rat. As to the indices of cerebral hypoperfusio n, we initially used cranial window method to measure the diameter of blood vessels. However, this method activated the PMNLs due to opening the cranium. Instead, we evaluated brain oxygenation by near infrared spectroscopy non-envasively. Under 0.5 MAC isoflurane anesthesia total Hb (tHb) and HbO_2 (oxy-hemoglobin) significantly decreased at 120 min after reoxygenation, suggesting that post-reoxygenation hypoperfusion occurred. The CD11b increased after reoxygenation at 0.5 MAC.There were significant negative relationshios between CD11b and tHb, and CD11b and HbO_2. In contrast, there was no change in tHb, HbO_2, and the expression of CD11b at. The 1.5 MAC.The ICAM-ldetected by enzyme immuno-staining increased after reoxygenation. However, we could not measure the expression of this CADM quantitatively. From these findings we suggested that anesthetics such as isoflurane and thiopental protected post ischemic or hypoxic brain hypoperfusion at least in part due to attenuation of the expression of cell adhesion molecules of PMNLs.