Introduction:
Type 2 diabetes mellitus (T2DM) is a major risk factor for stroke, yet it is unclear whether T2DM associated-poor outcome after stroke is related to unfavorable cerebral blood flow dynamics. The current study aimed to investigate the effect of T2DM on acute blood flow dynamics and stroke outcome.
Methood:
Adult male db/db and db/+ mice (8-9 weeks of age) were subjected to permanent distal middle cerebral artery occlusion (pMCAo). Neurologic deficit was assessed with a 5-point scoring system (0 to 4) and infarction volume was determined at 48 hours after pMCAo by TTC staining. Hemodynamics was evaluated by laser doppler flowmetry. The number of connecting collateral vessels, functional microvascular network morphology, and vessel area density of the ischemic hemisphere were determined by DiI-labeling, and optical coherence tomography (OCT), respectively.
Results:
db/db mice had a higher baseline blood glucose level (341±39.7 vs. 172±26.5 mg/dl,
p
<0.01) and a larger infarct volume after pMCAO compared to db/+ mice (69.5±5.4 vs. 51.0±3.1 mm
3
,
p
<0.01). Neurologic deficit did not differ between groups at 2 hours after pMCAO, but was significantly worse in the db/db at 24 hours after pMCAo compared to db/+ mice (1.9±0.1 vs. 1.4±0.2,
p
<0.05), correlated with lower rCBF in the core of the MCA territory at 24 and 48 hours (10.9%±1.1 vs. 14.4%±0.8,
p
<0.05 and 9.5%±1.0 vs. 14.1%±1.2,
p
=0.01). Ipsilateral functional microvascular density as detected by OCT did not differ between groups at one hour after occlusion but was significantly lower in the db/db mice at 24 hr after pMCAo (
p
<0.05). However, we did not observe a significant difference in the number of connecting collateral arteries between groups at 48 hours after pMCAo in this age group.
Conclusion:
Our results demonstrate that T2DM is associated with lower rCBF and lower density of functional blood vessels during the acute phase of pMCAo, which might in part, contribute to the observed worse outcome in the db/db mice. Ongoing experiments will investigate whether T2DM affects the flow dynamics in individual collateral following MCA occlusion and outward remodeling of the collateral vessels.
Thrombus Formation and Blood Flow Dynamics in Microvessels
