Exacerbated brain damage, edema and inflammation in type-2 diabetic mice subjected to focal ischemia

Abstract

J. Neurochem. (2011) 116, 499–507. Abstract One of the limiting factors in stroke therapeutic development is the use of animal models that do not well represent the underlying medical conditions of patients. In humans, diabetes increases the risk of stroke incidence as well as post‐stroke mortality. To understand the mechanisms that render diabetics to increased brain damage, we evaluated the effect of transient middle cerebral artery occlusion in adult db/db mice. The db/db mouse is a model of type‐2 diabetes with four times higher blood sugar than its normoglycemic genetic control(db/+ mouse). Following transient middle cerebral artery occlusion, the db/db mice showed significantly higher mortality, bigger infarcts, increased cerebral edema, worsened neurological status compared to db/+ mice. The db/db mice also showed significantly higher post‐ischemic inflammatory markers (ICAM1+ capillaries, extravasated macrophages/neutrophils and exacerbated proinflammatory gene expression) compared to db/+ mice. In addition, the post‐ischemic neuroprotective heat‐shock chaperone gene expression was curtailed in the db/db compared to db/+ mice.

Dehydration is a strong predictor of long‐term prognosis of thrombolysed patients with acute ischemic stroke

“…Additionally, high blood glucose levels was also found to be an independent risk factor of prognosis of thrombolysed patients with acute ischemic stroke in our study, which was consistent with previous reports (Bruno & Hamilton, 2001; Bruno et al., 1999; Demchuk et al., 1999; Kase et al., 2001). Higher blood glucose levels may lead to secondary tissue acidosis and oxygen‐derived free radicals increase, resulting in brain cell metabolism disorders, increased brain tissue damage, and the blood–brain barrier disruption (Godoy, Behrouz, & Di Napoli, 2016; Tureyen et al., 2011). Furthermore, the study shows that higher SBP levels before thrombolysis may be detrimental to poor outcome.…”

Blood–Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke

“…In addition, a higher incidence of poststroke edema was reported in patients with DM 22. Similarly, in type 2 diabetes mellitus (T2DM) mice subjected to stroke, a significant increase in both ipsilateral and contralateral brain water content was observed 23. Additional complications such as hypertension can exacerbate cerebral edema after stroke in patients with DM 23.…”

“…Similarly, in type 2 diabetes mellitus (T2DM) mice subjected to stroke, a significant increase in both ipsilateral and contralateral brain water content was observed 23. Additional complications such as hypertension can exacerbate cerebral edema after stroke in patients with DM 23. Understanding the mechanism and consequences of BBB disruption after stroke and in particular diabetic stroke are essential to developing therapeutics 24, 25…”

Hemorrhagic transformation of ischemic stroke

“…Most likely the ROS induction [88], a modified leukocyte function [89], impaired BBB permeability [90], microvascular remodeling, altered vessel structure and angiogenesis via VEGF and peroxinitrit signaling [91], involving membrane-type matrix metalloprotease (MT-MMP) and c-src kinase activation [92] and further inflammatory cascades contribute to the HT [93]. A further study reports that after streptozotocin induced hyperglycemia and transient MCA occlusion the infarct volume and area was not altered by hyperglycemia, but the HT volume was significantly higher.…”