Cerebral Blood Flow Restoration and Reperfusion Injury After Ultraviolet Laser–Facilitated Middle Cerebral Artery Recanalization in Rat Thrombotic Stroke

Abstract

Background and Purpose-A reversible model of focal thrombotic stroke was developed in the rat and examined for histological evidence of reperfusion injury after clinically relevant times of recanalization. Methods-The distal middle cerebral artery of 28 male Sprague-Dawley rats was occluded by 562-nm laser-driven photothrombosis for 0.5, 2, and 3 hours or permanently (each nϭ7) and was recanalized by 355-nm UV laser irradiation. Occlusive material was examined by transmission electron microscopy. Cortical cerebral blood flow was monitored by laser-Doppler flowmetry. Brain infarcts were examined histologically at 3 days. Results-After occlusion, cortical cerebral blood flow was reduced to 33Ϯ4% of baseline for all groups and was restored to 82Ϯ9%, 75Ϯ3%, and 93Ϯ7% of baseline for the 0.5-, 2-, and 3-hour groups, respectively, following recanalization after 29Ϯ8, 38Ϯ20, and 70Ϯ33 minutes of UV laser irradiation. The thrombotic occlusion contained compactly aggregated platelets but no fibrin, with length (1.2 to 1.8 mm) proportional to the ischemic period. During recanalization, microchannels containing erythrocytes and scattered leukocytes and bordered by intact disaggregated platelets infiltrated the thrombus. Infarct volumes (mm 3 ) at 3 days were 12Ϯ3 for the permanent case and 8Ϯ4, 24Ϯ3, and 30Ϯ9 for the 0.5-, 2-, and 3-hour cases, respectively, thus demonstrating reperfusion injury histologically in the latter 2 groups. No hemorrhage was seen. Conclusions-UV laser-facilitated dissolution of a conventionally refractory platelet thrombus provides a novel and effective method for restoring blood flow without hemorrhagic complications during thrombotic stroke. This was the first observation of histologically confirmed reperfusion injury in such a model.

Inhibition of Intercellular Adhesion Molecule-1 Protein Expression by Antisense Oligonucleotides Is Neuroprotective After Transient Middle Cerebral Artery Occlusion in Rat

“…30 This is understandable since leukocyte infiltration occurs much earlier after transient than permanent MCAO, and reperfusion predisposes the brain to an early inflammatory response. Reperfusion does not occur spontaneously in the majority of stroke patients, but recent studies showed promising results with thrombolytic protocols using prourokinase, 14 recombinant tPA, 15 UV laser, 16 and ultrasound. 17 Furthermore, postischemic hyperperfusion occurs in approximately 50% of patients by day 7 after intra-arterial thrombolysis-mediated recanalization.…”

“…Recent studies showed the benefit of thrombolysis with prourokinase, 14 recombinant tissue plasminogen activator (tPA), 15 UV laser, 16 and ultrasound. 17 Antisense oligonucleotides (ODNs) bind to a specific mRNA and prevent its translation to knockdown protein product locally in a time-dependent manner.…”

Photothrombotic Middle Cerebral Artery Occlusion and Reperfusion Laser System in Spontaneously Hypertensive Rats

“…12,13 This model encompasses appropriate physiological monitoring, associated risk factors for stroke (ie, hypertension and aging), and clinically relevant pathophysiology of thrombosis. A recent immense advance in the practice of the photothrombotic stroke method in the rat achieved by Watson et al 14 is the ultraviolet laser-induced reperfusion method. In the present study we discuss the usefulness of laser methods in establishing stroke models in SHR.…”

Induction of Reproducible Focal Ischemic Lesions in Neonatal Mice by Photothrombosis

“…In fact, a penumbral region that can be salvaged by pharmacologic intervention or by reperfusion after irreversible damage is produced using photothrombosis [Hao et al, 1992]. Reperfusion is an important clinical aspect of neonatal stroke [Jensen et al, 2003] and modifi cations of the photothrombotic stroke model have been developed to produce a nonpermanent, reversible lesion [Watson et al, 2002]. This study revealed that restoration of blood fl ow following permanent cerebral artery occlusion is achieved by using UV laser irradiation following photochemically induced thrombosis.…”