Astrocytic response to cerebral ischemia is influenced by sex differences and impaired by aging

Chisholm, Nioka C.; Sohrabji, Farida

doi:10.1016/j.nbd.2015.03.028

Cited by 71 publications

(66 citation statements)

References 154 publications

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“…The finding of increased GFAP expression in female rats given RmTBI suggests that they may have had elevated astrogliosis and inflammation relative to the male rats 30, 68. There is some evidence that biological sex can alter astrogliosis and inflammation after different forms of brain insult, including stroke and more severe TBI 69. However, these studies were undertaken in adults, and sex hormones are thought to play a central role in these differences 68, 69, 70.…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence that biological sex can alter astrogliosis and inflammation after different forms of brain insult, including stroke and more severe TBI 69. However, these studies were undertaken in adults, and sex hormones are thought to play a central role in these differences 68, 69, 70. As such, future studies are needed to examine how sex influences astrogliosis and inflammation in the developing brain.…”

Section: Discussionmentioning

confidence: 99%

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Sex matters: repetitive mild traumatic brain injury in adolescent rats

Wright

O’Brien

Shultz

et al. 2017

Ann Clin Transl Neurol

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ObjectiveWhether sex differences contribute to the heterogeneity of mild traumatic brain injury (mTBI) and repeated mTBI (RmTBI) outcomes in adolescents is unknown. Therefore, this study examined changes in, and differences between, male and female rats following single mTBI and RmTBI.MethodsRats were given a single mTBI, RmTBI (i.e., 3x), or sham injuries. Injuries were administered using a lateral impact model that mimics forces common in human mTBI. After the final injury, rats underwent extensive behavioral testing to examine cognition, motor function, and anxiety‐ and depressive‐like behavior. Postmortem analyses investigated gene expression and structural changes in the brain.ResultsMany of the outcomes exhibited a sex‐dependent response to RmTBI. While all rats given RmTBI had deficits in balance, motor coordination, locomotion, and anxiety‐like behavior, only male rats given RmTBI had short‐term working memory deficits, whereas only females given RmTBI had increased depressive‐like behavior. Volumetric and diffusion weighted MRI analyses found that while RmTBI‐induced atrophy of the prefrontal cortex was greater in female rats, only the male rats exhibited worse white matter integrity in the corpus callosum following RmTBI. Sex‐dependent changes in brain expression of mRNA for glial fibrillary acidic protein, myelin basic protein, and tau protein were also observed following injury.InterpretationThese findings suggest that in adolescent mTBI, sex matters; and future studies incorporating both male and females are warranted to provide a greater understanding of injury prognosis and better inform clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Wright

O’Brien

Shultz

et al. 2017

Ann Clin Transl Neurol

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“…37 Astrocyte morphology changes and GFAP expression increases progressively during aging in humans and rodents. 38,39 Pericytes Pericytes are BBB associated cells. During aging, pericytes show ultrastructural changes such as vesicular and lipofuscin-like inclusions 1,[40][41][42][43] ; an increased size of mitochondria 44 and a foamy transformation.…”

Section: Extracellular Matrixmentioning

confidence: 99%

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Erdő

Dénès

Lange

2016

J Cereb Blood Flow Metab

345

260

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The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication. KeywordsAging, blood-brain barrier, endothelial cells, neurodegenerative disorders, transport systems Structure of the blood-brain barrier (BBB)Homeostasis of the extracellular microenvironment in the neural tissue of the brain as well as its protection against neurotoxic compounds and variations in the composition of the blood are important for normal function of the neurons. It is warranted by a structure formed between blood and brain, which is therefore called the BBB.1 Clear evidence for the existence of this permeability barrier in the brain emerged in 1909 with the demonstration by Edwin Goldman (a South African-German) that a dye injected into the blood stream of a rat stained the whole body -except for the brain and spinal cord. The opposite was also true: injection of the dye into the cerebral ventricles stained the brain and spinal cord but not the rest of the body. 2,3 This occurs because most organs of the body are perfused by capillaries lined with endothelial cells (ECs) that have small pores (fenestrations) to allow for the rapid movement of small molecules into the organ interstitial fluid from the circulation. However, the capillary endothelium of the brain and spinal cord lack these pores because the ECs of brain capillary are connected to each other by continuous tight junctions (TJs), produced by the interaction of several transmembrane proteins that project into and seal the paracellular pathway.3-5 The interaction of these junctional proteins effectively blocks the free diffusion of

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“…Although the localization of the injury depends on the gestational age and the duration and the severity of the insult, hippocampus is one of the most commonly effected regions in the CNS after term neonatal HI, and increased hippocampal astrogliosis has been confirmed by up-regulation of the Glial Fibrillary Acidic Protein (GFAP) 3 d after the neonatal HI 7,10,12,13 . Sex differences in astrocyte function were shown in both neonates and adult rodents after cerebral ischemia 14,15 . In addition, male astrocytic susceptibility to in-vitro ischemia was shown by increased cell death compared to female cortical astrocytes in culture 16 .…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Mouse Hippocampal Astrocytes after <em>In-Vitro</em> Ischemia

Chanana

Tümtürk

Kintner

et al. 2016

JoVE

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Astrogliosis following hypoxia/ischemia (HI)-related brain injury plays a role in increased morbidity and mortality in neonates. Recent clinical studies indicate that the severity of brain injury appear to be sex dependent, and that the male neonates are more susceptible to the effects of HI-related brain injury, resulting in more severe neurological outcomes as compared to females with comparable brain injuries. The development of reliable methods to isolate and maintain highly enriched populations of sexed hippocampal astrocytes is essential to understand the cellular basis of sex differences in the pathological consequences of neonatal HI. In this study, we describe a method for creating sex specific hippocampal astrocyte cultures that are subjected to a model of in-vitro ischemia, oxygen-glucose deprivation, followed by reoxygenation. Subsequent reactive astrogliosis was examined by immunostaining for the Glial Fibrillary Acidic Protein (GFAP) and S100B. This method provides a useful tool to study the role of male and female hippocampal astrocytes following neonatal HI, separately. Video LinkThe video component of this article can be found at

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Astrocytic response to cerebral ischemia is influenced by sex differences and impaired by aging

Cited by 71 publications

References 154 publications

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Sex matters: repetitive mild traumatic brain injury in adolescent rats

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Sex Differences in Mouse Hippocampal Astrocytes after <em>In-Vitro</em> Ischemia

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