Tumor necrosis factor-alpha inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats.

Tumor necrosis factor-alpha inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats. Am J Physiol Heart Circ Physiol. 2014 Jul 11; Authors: Pires PW, Girgla SS, Moreno G, McClain JL, Dorrance AM Abstract Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophages depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN, 1.25mg/kg/day i.p. daily) or PBS (equivolume) for 6 weeks. MCA's myogenic tone generation, post-ischemic dilation and passive structure were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP+ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP+ETN after transient MCAO, despite an improvement in dilation of non-ischemic MCA. The increase in infarct size was linked ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research