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


CONCLUSIONS
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.
Mao
Y
Y
Department of Neurosurgery, Huashan Hospital, Shanghai Medical University, Shanghai 200040, China.
Zhou
L
L
Yang
G
G
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002545:Brain Ischemia / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D002544:Cerebral Infarction / Q000517:prevention & control*; D004195:Disease Models, Animal; D005822:Genetic Vectors; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D015424:Reperfusion / Q000379:methods; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*
D015815:Cell Adhesion Molecules; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D018696:Neuroprotective Agents; D012795:Sialoglycoproteins