Impaired Collateral Flow in Pial Arterioles of Aged Rats During Ischemic Stroke

Junqiang Ma,Ashfaq Shuaib,Ian R Winship,Yonglie Ma

doi:10.1007/s12975-019-00710-1

Junqiang Ma, Ashfaq Shuaib + Show 2 more

Open Access

https://doi.org/10.1007/s12975-019-00710-1

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Abstract

Cerebral collateral circulation and age are critical factors in determining outcome from acute ischemic stroke. Aging may lead to rarefaction of cerebral collaterals, and thereby accelerate ischemic injury by reducing penumbral blood flow. Dynamic changes in pial collaterals after onset of cerebral ischemia may vary with age but have not been extensively studied. Here, laser speckle contrast imaging (LSCI) and two-photon laser scanning microscopy (TPLSM) were combined to monitor cerebral pial collaterals between the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) in young adult and aged male Sprague Dawley rats during distal middle cerebral artery occlusion (dMCAo). Histological analysis showed that aged rats had significantly greater volumes of ischemic damage than young rats. LSCI showed that cerebral collateral perfusion declined over time after stroke in aged and young rats, and that this decline was significantly greater in aged rats. TPLSM demonstrated that pial arterioles narrowed faster after dMCAo in aged rats compared to young adult rats. Notably, while arteriole vessel narrowing was comparable 4.5 h after ischemic onset in aged and young adult rats, red blood cell velocity was stable in young adults but declined over time in aged rats. Overall, red blood cell flux through pial arterioles was significantly reduced at all time-points after 90 min post-dMCAo in aged rats relative to young adult rats. Thus, collateral failure is more severe in aged rats with significantly impaired pial collateral dynamics (reduced diameter, red blood cell velocity, and red blood cell flux) relative to young adult rats.

Highlights

Stroke disproportionately affects the elderly, with risk of stroke doubling every decade after the age of 55 in both sexes [1,2,3]
After distal middle cerebral artery occlusion (dMCAo), robust anastomotic connections between distal segments of the anterior cerebral artery (ACA) and middle cerebral artery (MCA) were observed in both groups
Pial collaterals were more robust in young rats (Fig. 3b, note the number of visible vessels following dMCAo in young vs. aged rats), and penumbral blood flow in young rat persisted through the imaging sessions in young rats

Summary

Introduction

Stroke disproportionately affects the elderly, with risk of stroke doubling every decade after the age of 55 in both sexes [1,2,3]. Elderly stroke patients exhibit significantly worse functional recovery and higher mortality compared to younger patients [1,2,3]. After occlusion of a cerebral vessel, tissue surrounding the nonviable infarct core in the penumbra remains viable due to blood flow via the cerebral collateral circulation [4]. Blood flow through the pial collaterals defines the degree of ischemia in the penumbra of cortical infarcts, and influences infarct growth, prognosis, and response to therapy [7, 10,11,12]. The DAWN and DEFUSE3 trials that evaluated patients following late

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