Perfusion of Ischemic Brain in Young and Aged Animals

Abstract

Background and Purpose Aging is an important determinant of ischemic stroke outcomes. Both clinical and experimental stroke studies have shown that aging negatively correlates with infarct volumes but is associated with worsened functional recovery after stroke. This may correspond to a differing cellular and molecular response to stroke in the aged vs. young brain. It was hypothesized in this study that the smaller injury seen in the aged ischemic brain is due to structural differences in microvasculature with aging or differences in intra-ischemic tissue perfusion. Methods Both young and aged C57BL6 mice were subject to middle cerebral artery occlusion (MCAO) modeling. Laser Speckle Flowmetry (LSF) was utilized to study the functional dynamics of cerebral perfusion, and FITC-dextran staining was performed to examine the structural change in microvasculature. In separate cohorts, Cresyl violet (CV) staining and immunohistochemistry with CD31 and IgG antibodies were applied to further assess the microvascular density and blood brain barrier breakdown after stroke. Results No difference in cerebral blood flow was seen at the baseline, intra-ischemically and post-reperfusion in young vs. aged mice. FITC-dextran and CD31 staining did not show significant differences in the microvascular density between young and aged ischemic brains. More extravasation of IgG through the BBB was found in the young vs. aged cohort at both 24 and 72 hours after stroke. Conclusions Cerebrovascular dynamics and perfusion are not responsible for the different stroke phenotypes seen in the young vs. aged animals, which may be more related to different levels of BBB breakdown.

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke

“…Young (10–12 wks) and aged (24 mos) male mice were subjected to focal transient cerebral ischemia by 60 min of reversible MCA occlusion under Isofluorane anesthesia as previously described [11]. In order to achieve equivalent levels of occlusion, 0.21 mm and 0.23 mm silicone coated sutures were used in young and aged mice, respectively [11]. Rectal temperatures were maintained at approximately 37° C during surgery and ischemia with an automated temperature control feedback system.…”

Models and mechanisms of vascular dementia

“…It may be important to factor in age, and study aged animals in VaD animal models. However, some of the difficulties involved in studying aged animals include mortality, severe neurological deficits after stroke, occurrence of tumors, and the resulting requirement of using increased animal number to be conclusive of results [118–120]. …”

Inhibition of miR-181a protects female mice from transient focal cerebral ischemia by targeting astrocyte estrogen receptor-α

“…Importantly, a similar sexual dimorphism has been identified for injury outcome in rodent models of stroke. Overall, adult female rodents have smaller infarct volumes and improved neurobehavioral outcomes following transient cerebral ischemia than their age-matched male counterparts (Alkayed et al, 1998; Selvamani et al, 2014; Xiong et al, 2011), however this effect is reversed in aged female rodents (Manwani et al, 2014). Delineating the mechanisms that regulate the differences between males and females in risk and outcome following stroke may yield new insight and more effective therapeutics.…”