The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

Abstract

Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke.

Keywords: animal model; embolization; hyperglycemia; lacunar stroke; microsphere.

Figure 2

The 16-day time-course of the blood glucose levels in 4 rats with streptozocin-induced hyperglycemia. The blood glucose levels reached a steady state at 3 days after streptozocin injection, and exhibited minimal fluctuation until day 16.

Figure 3

Plasma glucose levels before lacunar stroke and diffuse infarction induction. The dashed line indicates the hyperglycemic groups and the blank line indicates the normoglycemic controls. The data is expressed as mean ± standard error for each group (n = 5-9). *p < 0.05.

Figure 4

The effects of hyperglycemia on infarct volume in lacunar stroke and diffuse infarction. A) The TTC-stained serial sections revealed different effects of hyperglycemia on infarct volume in lacunar stroke and diffuse infarction. B) Quantitative analysis of hyperglycemia's effects on infarct volume in various brain regions.

Fig 5

The relationship between infarct volume in various brain regions and the blood glucose levels in lacunar stroke and diffuse infarction. A significant and positive correlation between total infarct volume and glucose levels is clear in diffuse infarction (r² = 0.38, p = 0.02). A significant and negative correlation between total infarct volume and glucose levels is clear in lacunar stroke (r² = 0.26, p = 0.01). A) Lacunar stroke. B) Diffuse infarction. A p-value of <0.05 indicates a significant correlation between the two groups via correlation analysis.

Fig 6

The effects of hyperglycemia on the neurologic deficits immediately after lacunar stroke and diffuse infarction. A) A 24-h time-course of the neurologic scores in lacunar stroke. B) A 24-h time-course of the neurologic scores in diffuse stroke. *Significantly different from the control groups (p < 0.05).

Fig 1

Embolic stroke was induced by injecting an artificial embolus into the rat brain during full consciousness. (A) The morphological characteristics of the chitin/PLGA microparticles. (B) The PE-10 tube was inserted into right internal carotid artery from the right external carotid artery, in order to reach the middle cerebral artery. (C) The tube was then carefully fixed into the external carotid artery, and residual PE-10 tubing was exposed on the neck skin to facilitate the microparticle injection. An appropriate amount of heparin was used to prevent clotting on the PE-10 tube.