[Attenuation of reperfusion injury in the mouse transfected interleukin-1 receptor antagonist]

Abstract

Objective: To investigate the therapeutic effects of overexpression of interleukin-1 receptor antagonist (IL-1ra), administered by gene transfer, on the transient cerebral ischemic injury in an experimental mice suture model.

Methods: Adenovirus vector encoding human IL-1ra gene (Ad.RSVIL-1ra) or LacZ gene (Ad.RSVLacZ) or normal saline was administered by injection into the right lateral ventricle in adult CD-1 mice. Five days after the virus injection, the mice received 1 h transient middle cerebral artery occlusion with 23 h reperfusion. Surface cerebral blood flow was measured using laser Doppler flowmetry. Brain infarct volume was evaluated on the sections with hematoxylin-eosin staining. Blood-brain barrier (BBB) permeability was determined using immunostaining of extravasated endogenous albumin. The number of intracellular adhesion molecular-1-positive vessels was determined by immunohistochemistry.

Results: The infarct volume in the Ad. RSVIL-1ra transfected mice was markedly reduced compared with the Ad. RSVLacZ transfected or saline mice (36.0 +/- 5.3 mm(3) vs 60.0 +/- 6.2 mm(3), 69.5 +/- 6.3 mm(3), P < 0.05). BBB disruption area was also smaller in the Ad. RSVIL-1ra transfected mice than in the Ad. RSVLacZ transfected and saline mice (P < 0.05). The expression of intracellular adhesion molecular-1 (ICAM-1) positive vessels in the ischemic cortex and basal ganglia was greatly attenuated in the Ad. RSVIL-1ra transfected mice (cortex: 135 +/- 23, vs 311 +/- 40 and 357 +/- 51 pound sterling basal ganglia: 90 +/- 21, vs 207 +/- 43 and 259 +/- 43, P < 0.05.

Conclusion: IL-1ra has neuroprotective property during ischemia/reperfusion injury. Overexpression of IL-1ra via gene transfer can attenuate the expression of ICAM-1 in the ischemic area.