The adenosine 2A receptor agonist ATL-146e attenuates experimental posthemorrhagic vasospasm

Chang C., Dumont A. S., ŞİMŞEK S., Titus B. J., Kwan A., Kassell N. F., ...Daha Fazla

Neurosurgery, cilt.60, sa.6, ss.1110-1117, 2007 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 60 Sayı: 6
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1227/01.neu.0000255467.22387.5c
  • Dergi Adı: Neurosurgery
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1110-1117
  • Anahtar Kelimeler: adenosine, adenosine 2A receptor, adenosine agonist, ATL-146e, cerebral vasospasm, femoral artery, inflammation, subarachnoid hemorrhage, ACTIVATED PROTEIN-KINASE, ISCHEMIA-REPERFUSION INJURY, VASCULAR SMOOTH-MUSCLE, SENSITIVE POTASSIUM CHANNELS, MEDIATED TISSUE PROTECTION, RABBIT BASILAR ARTERY, CD4(+) T-CELLS, SUBARACHNOID HEMORRHAGE, CEREBRAL VASOSPASM, A(2A) RECEPTOR
  • Lokman Hekim Üniversitesi Adresli: Hayır

Özet

OBJECTIVE: Selective adenosine 2A receptor agonists, such as ATL-146e, are known to be potent anti-inflammatory agents devoid of systemic side effects and have been used clinically in a number of disease states. However, adenosine 2A receptor agonists have not been studied in the treatment of cerebral vasospasm after subarachnoid hemorrhage. The present study investigated the efficacy of ATL-146e in the prevention of leukocyte infiltration and attenuation of posthemorrhagic vasospasm. METHODS: The rodent femoral artery model of vasospasm was used. Forty male Sprague-Dawley rats were randomly assigned to four different groups (vehicle, 1 ng/kg/min, 10 ng/kg/min, or 100 ng/kg/min ATL-146e administered via subcutaneous osmotic minipump). Vasospasm was evaluated at posthemorrhage Day 8 (period of peak constriction) by calculating the lumen cross-sectional area (expressed as percent change in luminal area: ratio of blood-exposed vessel to normal saline-exposed vessel) and radial wall thickness. Immunostaining with anti-CD45 monoclonal antibody to detect leukocytes was used to evaluate localized inflammation. RESULTS: Significant vasospasm was noted in the vehicle-treated (blood-exposed) control group (78.5%, P < 0.001; expressed as a ratio of luminal area of the saline [no blood] control), but not in the ATL-146e-treated groups (lumen ratio to control: 105.0, 83.4, and 91.3% for the 1, 10, and 100 ng/kg/min groups, respectively). Additionally, infiltration of inflammatory cells was reduced significantly and radial wall thickness was decreased in the ATL-146e-treated groups compared with the vehicle-treated control group. CONCLUSION: Selective activation of the adenosine 2A receptor with ATL-146e prevented posthemorrhagic vasospasm and reduced leukocyte infiltration in this experimental model. This agent is worthy of further investigation and lends credence to the hypothesis supporting a role for inflammation in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. Copyright © by the Congress of Neurological Surgeons.