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J Neurosci. 2015 Mar 4;35(9):3851-64. doi: 10.1523/JNEUROSCI.3838-14.2015.

Impaired leptomeningeal collateral flow contributes to the poor outcome following experimental stroke in the Type 2 diabetic mice.

Author information

1
Department of Neurological Surgery, University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan, and.
2
Department of Neurological Surgery, University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California 94121.
3
Departments of Bioengineering and Ophthalmology, University of Washington, Seattle, Washington 98195.
4
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan, and.
5
Department of Neurological Surgery, University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, jialing.liu@ucsf.edu.

Abstract

Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects.

KEYWORDS:

Doppler OCT; MCAO; anastomosis; arteriogenesis; metabolic syndrome; vascular remodeling

PMID:
25740515
PMCID:
PMC4348184
DOI:
10.1523/JNEUROSCI.3838-14.2015
[Indexed for MEDLINE]
Free PMC Article

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