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Abstract
Objective: To examine the effects of intraventricular pre-treatment with recombinant adeno-associated virus vectors encoding VEGF (rAAV-VEGF) on early stroke in a rat model of transient middle cerebral artery occlusion (tMCAO).
Methods: rAAV-VEGF, rAAV-null or physiologic saline was delivered into the lateral ventricle of 93 Wistar rats, respectively. Eight weeks later, the rats were subjected to tMCAO for 2 hours. During the early stage following ischemic reperfusion, intracranial pressure (ICP) and brain water content were measured to make a correlation analysis, T2-weighted MRI was performed to observe cerebral edema volume, and TTC-derived cerebral infarct volume and modified neurological severity scores (NSS) were determined to evaluate the therapeutic efficacy of rAAV-VEGF in tMCAO.
Results: Twenty-four hours following tMCAO, the rAAV-VEGF group, with VEGF overexpression in the rats brain, showed a significantly increase in ICP, brain water content and cerebral edema volume compared with two control groups (p<0.05). The ICP significantly correlated with the brain water content in the infarct hemisphere in all three groups during 24 hours following tMCAO (r=0.93, p<0.05). Forty-eight hours following tMCAO, a 1.3-fold larger infarct volume and 1.3-fold higher NSS were observed in the rAAV-VEGF group than both control groups (p<0.05).
Conclusion: Our results indicate that intraventricular rAAV-VEGF pre-treatment can result in deleterious intracranial hypertension and augment secondary ischemic insults at the early stage of tMCAO, and pre-ischemic VEGF gene transfer via intraventricular approach may not be a favorable therapeutic strategy for tMCAO which should be adopted with caution or avoided in experimental stroke.