Cerebral White Matter Injuries Following a Hypoxic/Ischemic Insult During the Perinatal Period: Pathophysiology, Prognostic Factors, and Future Strategy of Treatment Approach. A Minireview

Zammit, Christian; Muscat, Richard; Sani, Gabriele; Pomara, Cristoforo; Valentino, Mario

doi:10.2174/1381612821666150105122008

Cited by 7 publications

(5 citation statements)

References 118 publications

(132 reference statements)

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“…Hypoxia–ischemia leads to necrotic cell death, inflammation, brain edema, excitotoxicity, and apoptotic cell death [35, 36]. Because the pyramidal neurons in the hippocampal CA1 region are vulnerable to cerebral ischemia[37], so we assess the effect on apoptosis in our study, the hypercapnia therapy has also been reported to have an antiapoptotic effect by our previous work [14].…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia

et al. 2016

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Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30–39 mmHg, 40–49 mmHg, 50–59 mmHg, and 60–69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60–80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO2 < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood–brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO2 > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg); especially under mild hypoxemia (PaO2 > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

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Section: Discussionmentioning

confidence: 99%

Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia

et al. 2016

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“…In multiple sclerosis, a chronic autoimmune inflammatory disease of the brain-although the grey matter is also affected (35)-infiltrating leukocytes are mainly found in white matter lesions. The white matter is also predominantly affected in repetitive brain trauma (44), premature brain injury (46), and a wide spectrum of pediatric neuroinflammatory diseases (37).…”

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confidence: 99%

Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study

Nyúl‐Tóth

Suciu

Molnár

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.

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“…At physiological concentrations in the body, ROS are regulators of various physiological functions. In a chronic state of oxidative stress, reactive species can become harmful because they oxidize proteins and lipids and can damage DNA [7][8][9]. Reactive species may also mediate signaling, leading to microglia and primary astrocyte activation [10], resulting in a high secretion of pro-inflammatory cytokines and chemokines [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Role of Vitamin E and the Orexin System in Neuroprotection

et al. 2021

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Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction of specific receptors such as the OX2-OX2R complex, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.

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Cerebral White Matter Injuries Following a Hypoxic/Ischemic Insult During the Perinatal Period: Pathophysiology, Prognostic Factors, and Future Strategy of Treatment Approach. A Minireview

Cited by 7 publications

References 118 publications

Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia

Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia

Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study

Role of Vitamin E and the Orexin System in Neuroprotection

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