Postischemic Hyperperfusion Does Not Necessarily Indicate Good Recovery of Brain Tissue. From the Viewpoint of PKA-Mediated Intracellular Signal Transduction

  • Kortaro Tanaka
  • Yasuo Fukuuchi
  • Shigeru Nogawa
  • Eiichiro Nagata
  • Daisuke Ito
  • Shigeaki Suzuki
  • Tomohisa Dembo
  • Arifumi Kosakai
Conference paper
Part of the Keio University Symposia for Life Science and Medicine book series (KEIO, volume 6)

Summary

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) plays an important role in intracellular signal transduction and has been found to be highly susceptible to acute ischemic insult. In the present study we examined the relation between postischemic cerebral blood flow (CBF) and the binding capacity of PKA with cAMP in experimental cerebral ischemia. Sprague-Dawley rats were divided into three groups: a middle cerebral artery occlusion (MCAO) group (n = 7), a recirculation group (n = 10), and a sham group (n = 7). The former two groups were subjected to occlusion of the MCA by the intraluminal suture method for 5.0 and 1.5 h, respectively. In the recirculation group, the suture was withdrawn to reperfuse the brain for 3.5 h. At the end of the experiments, CBF was measured by the 14Ciodoantipyrine method in each group. The autoradiograms of CBF and 3H-cAMP binding were obtained from the serial brain sections cut on a cryostat. The recirculation group was divided into two subgroups, a hyperCBF group and a not-hyperCBF group, based on CBF in the somatosensory cortex on the ischemic side (CBFi). If CBFi was higher than the corresponding mean value of CBF in the sham group (128.5 ml/100g/min), the animal was classified as hyperCBF. Other animals in the recirculation group were classified as not-hyperCBF. The hyperCBF group revealed a significant reduction in cAMP binding (compared to the not-hyperCBF and sham groups) in the cerebral cortex and caudate-putamen. The reduction in cAMP binding in the caudate-putamen, which was located in the ischemic core, was even more severe in the hyperCBF group than that in the MCAO group. The infarct area in the hyperCBF group was significantly larger in brain regions, especially in the caudate-putamen, than that in the not-hyperCBF group, and it tended to be even larger than that in the MCAO group. Taken together, postischemic hyperperfusion that persists for a while (e.g., 3.5 h), as observed in the present study, may be rather harmful in the ischemic core.

Key words

Postischemic hyperperfusion Cerebral ischemia Cyclic AMP Cyclic AMP-dependent protein kinase Signal transduction 
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Copyright information

© Springer Japan 2001

Authors and Affiliations

  • Kortaro Tanaka
    • 1
  • Yasuo Fukuuchi
    • 1
  • Shigeru Nogawa
    • 1
  • Eiichiro Nagata
    • 1
  • Daisuke Ito
    • 1
  • Shigeaki Suzuki
    • 1
  • Tomohisa Dembo
    • 1
  • Arifumi Kosakai
    • 1
  1. 1.Department of Neurology, School of MedicineKeio UniversityTokyoJapan

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