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1.
J Cereb Blood Flow Metab ; 44(4): 508-515, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37873754

ABSTRACT

Perivascular spaces mediate a complex interaction between cerebrospinal fluid and brain tissue that may be an important pathway for solute waste clearance. Their structural or functional derangement may contribute to the development of age-related neurogenerative conditions. Here, we employed a non-invasive low b-value diffusion-weighted ECG-gated MRI method to capture perivascular fluid movement around the middle cerebral artery of the anaesthetised rat brain. Using this method, we show that such MRI estimates of perivascular fluid movement directionality are highly sensitive to the cardiac cycle. We then show that these measures of fluid movement directionality are decreased in the angiotensin-II pharmacological model of acute hypertension, with an associated dampening of vessel pulsatility. This translational MRI method may, therefore, be useful to monitor derangement of perivascular fluid movement associated with cardiovascular pathologies, such as hypertension, in order to further our understanding of perivascular function in neurology.


Subject(s)
Hypertension , Middle Cerebral Artery , Rats , Animals , Magnetic Resonance Imaging , Hypertension/metabolism , Diffusion , Brain/blood supply , Cerebrospinal Fluid/metabolism
2.
Acta Neuropathol ; 128(2): 247-66, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24622774

ABSTRACT

Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4(+) T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8(+) T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4(+) T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models.


Subject(s)
Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/pathology , Multiple Sclerosis/pathology , Aging/pathology , Aging/physiology , Animals , CD4 Antigens/metabolism , CD8 Antigens/metabolism , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cuprizone , Encephalomyelitis, Autoimmune, Experimental/immunology , Gene Expression , Iron/metabolism , Lipopolysaccharides/immunology , Macrophages/pathology , Macrophages/physiology , Mice, Inbred C57BL , Microglia/pathology , Microglia/physiology , Multiple Sclerosis/immunology , Myelin-Oligodendrocyte Glycoprotein/immunology , Oxidative Stress/physiology , Peptide Fragments/immunology , Rats , Rats, Inbred Lew , Respiratory Burst/physiology , T-Lymphocytes/physiology , T-Lymphocytes/transplantation
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