Ischemia-induced Angiogenesis is Attenuated in Aged Rats

Tang, Yaohui; Wang, Liuqing; Wang, Jixian; Lin, Xiaojie; Wang, Yongting; Jin, Kunlin; Yang, Guo Yuan

doi:10.14336/ad.2015.1125

Cited by 28 publications

(15 citation statements)

References 47 publications

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“…Similarly, the balance of angiogenesis and pruning that we observed in visual cortex would predict an increase in vascular density, yet we observed a 2% decrease with age. It is therefore clear that angiogenic rates must also change with age, something that has been previously reported in the literature (Black et al, 1989;Harb et al, 2013;Tang et al, 2016). As such, further characterization of how, why, and where the vasculature changes with age (e.g.…”

Section: Discussionmentioning

confidence: 53%

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

Schager

Brown

2020

J Cereb Blood Flow Metab

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Vessel loss in the aging brain is commonly reported, yet important questions remain concerning whether there are regional vulnerabilities and what mechanisms could account for these regional differences, if they exist. Here we imaged and quantified vessel length, tortuosity and width in 15 brain regions in young adult and aged mice. Our data indicate that vessel loss was most pronounced in white matter followed by cortical, then subcortical grey matter regions, while some regions (visual cortex, amygdala, thalamus) showed no decline with aging. Regions supplied by the anterior cerebral artery were more vulnerable to loss than those supplied by middle or posterior cerebral arteries. Vessel width and tortuosity generally increased with age but neither reliably predicted regional vessel loss. Since capillaries are naturally prone to plugging and prolonged obstructions often lead to vessel pruning, we hypothesized that regional susceptibilities to plugging could help predict vessel loss. By mapping the distribution of microsphere-induced capillary obstructions, we discovered that regions with a higher density of persistent obstructions were more likely to show vessel loss with aging and vice versa. These findings indicate that age-related vessel loss is region specific and can be explained, at least partially, by regional susceptibilities to capillary plugging.

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Section: Discussionmentioning

confidence: 53%

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

Schager

Brown

2020

J Cereb Blood Flow Metab

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“…Aging is a multifaceted process associated with cellular, metabolic, and structural changes in the brain [43,44]. Many factors, such as increased oxidative stress, proinflammatory cytokine expression, and reduced cell survival, have been considered important factors contributing to increased ischemic brain injury in aged animals [43,45].…”

Section: Discussionmentioning

confidence: 99%

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

Shuaib

et al. 2019

Transl. Stroke Res.

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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.

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“…Ischemic stroke is one of the leading causes of death and adult disability around the world, which leads to massive cell death and complex pathological changes . Microglial activation is one of the characteristics at the acute stage of stroke .…”

Section: Introductionmentioning

confidence: 99%

P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis

et al. 2020

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Introduction Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown. Aim To investigate whether P2Y6 receptor‐mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke. Results The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL‐1α, IL‐1β, IL‐6, IL‐10, TNF‐α, TGF‐β, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor‐mediated phagocytosis. Conclusion Our results indicate that P2Y6 receptor‐mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.

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Ischemia-induced Angiogenesis is Attenuated in Aged Rats

Cited by 28 publications

References 47 publications

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

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

P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis

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