Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome

Abstract

Background: Diabetes mellitus (DM) is associated with a wide range of microvascular abnormalities in the brain. These include the dysfunction of the blood brain barrier (BBB). In this study, we test the hypotheses that disruption of the BBB in patients presenting with acute stroke is common in patients with DM and is related to outcome. Methods: Sixty-two consecutive patients with ischemic stroke in the middle cerebral artery territory were enrolled within 3-7 days after onset. In ischemic lesion, BBB disruption was detected by parenchymal enhancement (PE) on 5 min delayed post-contrast T1 weighted imaging. National Institute of Health Stroke Score (NIHSS) assessed neurologic impairment on admission. Clinical outcome at 3 months was classified as unfavorable if the modified Rankin scale was >1. The independent factors associated with clinical outcome were analyzed using multivariate logistic regression analysis and OR with its 95% CIs were estimated. Results: An unfavorable stroke outcome was found in 19 diabetic patients and 21 non-diabetic patients. Diabetic patients had a significantly higher frequency of PE than non-diabetic patients (58.6 vs. 27.3%, p = 0.013) and DM was independently associated with PE (OR 4.40; 95% CI 1.22-15.83; p = 0.023). PE was significantly more common in diabetic patients with unfavorable stroke outcome (73.7%) than in other 3 subgroups: diabetic patients with favorable stroke outcome (30.0%), non-diabetic patients with favorable stroke outcome (38.1%) and unfavorable stroke outcome (8.3%; p = 0.002). PE was independently associated with unfavorable outcome (UO) in diabetic stroke (DS; OR 7.04; 95% CI 1.20-41.52; p = 0.031). Admission NIHSS score was associated with UO in non-DS (NDS) (OR 1.71; 95% CI 1.10-2.66; p = 0.017). Conclusions: Compared with NDS, DS had increased BBB disruption defined by the presence of PE. A different form of the relationship between admission NIHSS and UO in NDS, BBB disruption was related with UO in diabetic patients after stroke.

Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury

“…As a multi-faceted metabolic syndrome, DM has detrimental effects on microvasculature. Prolonged hyperglycemia facilitates the pathophysiology and development of various PNS and CNS disorders 36 . In the co-culture system of HBMEC with human astrocytes, hyperglycemia induced exacerbation of barrier dysfunction was shown to be present as seen by a decrease of transendothelial electrical resistance and increase of EB extravasation 37 .…”

Neutralization of interleukin‐9 ameliorates experimental stroke by repairing the blood–brain barrierviadown‐regulation of astrocyte‐derived vascular endothelial growth factor‐A

“…Structural and functional impairment of the BBB, characterized by disruption of endothelial cell-associated connections, is one of the hallmarks of neurologic disease (36), whereas the severity of BBB disruption has been shown to correlate positively with the severity of IS (37)(38)(39). Our study also found that anti-IL-9 mAb improves the destruction of the BBB after stroke and that its mechanism is related to active repair of the damaged TJPs in brain tissue, which is different from the effects of anti-IL-9 mAb on inflammatory diseases of the CNS.…”

Association between Increased Matrix Metalloproteinase-9 (MMP-9) Levels with Hyperglycaemia Incidence in Acute Ischemic Stroke Patients

“…Previous studies have shown that an up-regulation of MMP-9 activity contributes to the exacerbation of vascular damage in diabetic patients, but not in patients with acute hyperglycemia [ 29 ]. This vascular damage disrupted the blood-brain barrier and led to an unfavourable outcome in diabetic patients [ 30 ].…”