Abstract
Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI.
Highlights
In the clinic, the vast majority (90–95%) of diabetic patients have type 2 diabetes mellitus (T2DM) [1]
Volumes of the ischemic lesion demarcated from T2 maps did not exhibit any significant differences (p>0.1), as indicated in Fig 1A, within 5 weeks after stroke between the bone marrow stromal cells (BMSC) and phosphate-buffered saline (PBS) treated T2DM rats
After the onset of ischemia, lesion volumes experienced a sharp decline from 1d to 1w in all rats (Fig 1A), since brain edema, which caused swelling of the ipsilateral brain hemisphere to approximately 16% greater (p
Summary
The vast majority (90–95%) of diabetic patients have type 2 diabetes mellitus (T2DM) [1]. Diabetes with concomitant hyperglycemia is a chronic vascular disease [1]. Hyperglycemia induces a variety of biochemical changes within endothelial cells, including. Cell Therapy Reduces BBB Damage in T2DM Stroke Rats the authors and does not necessary represent the official view of the National Institute of Health. Those in the cerebral vasculature [2], which instigates a cascade of events leading to vascular endothelial cell dysfunction, and increased vascular permeability in various vascular beds in humans and animal models [3]. Multiple cell and molecular pathways are involved in the diabetes-related changes in the blood-brain barrier (BBB) [4]
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