Regional changes in the metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: A quantitative proton MRS study

Macrì, Monica; d’Alessandro, Nicola; Giulio, Camillo Di; Iorio, Patrizia Di; Luzio, S. Di; Giuliani, Patricia; Bianchi, G.; Esposito, Ennio

doi:10.1016/j.neurobiolaging.2005.01.007

Cited by 36 publications

(34 citation statements)

References 33 publications

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“…Our data would support that the quantified T 2 changes are a cumulative change in water content and protein in the ischemic tissue associated with significant BBB breakdown. The relation between age of rodent and infarct size has been inconclusive; some studies in rats found that cerebral infarction in aged rats was no different from young animals (Sutherland et al, 1996;Rosen et al, 2005), while others have documented increased infarct size in aged animals (Macri et al, 2006). We observed only increased infarct size in elderly rodents that were administered tPA when compared with their agematched saline controls, but the survival period of 24 hours was relatively short.…”

Section: Discussioncontrasting

confidence: 58%

Quantitative MRI Reveals the Elderly Ischemic Brain is Susceptible to Increased Early Blood—Brain Barrier Permeability Following Tissue Plasminogen Activator Related to Claudin 5 and Occludin Disassembly

Kaur

Tuor

Zhao

et al. 2011

J Cereb Blood Flow Metab

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Great uncertainty exists as to whether aging enhances the detrimental effects of tissue plasminogen activator (tPA) on vascular integrity of the ischemic brain. We hypothesized that tPA treatment would augment ischemic injury by causing increased blood-brain barrier (BBB) breakdown as determined by quantitative serial T(1) and T(2) magnetic resonance imaging (MRI), and the transfer constant for gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) from blood to brain in aged (18 to 20 months) compared with young (3 to 4 months) Wistar rats after middle cerebral artery occlusion, mediated through the acute disassembly of claudin 5 and occludin. Increased T(2) values over the first hour of postreperfusion were independently augmented following treatment with tPA (P<0.001) and aging (P<0.01), supporting a synergistic effect of tPA on the aged ischemic brain. Blood-brain barrier permeability for Gd-DTPA (K(Gd)) was substantial following reperfusion in all animal groups and was exacerbated by tPA treatment in the elderly rat (P<0.001). The frequency of hematoma formation was proportionately increased in the elderly ischemic brain (P<0.05). Both tPA and age independently increased claudin 5 and occludin phosphorylation during ischemia. Early BBB permeability detected by quantitative MRI following ischemic stroke is enhanced by increased age and tPA and is related to claudin 5 and occludin phosphorylation.

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Section: Discussioncontrasting

confidence: 58%

Quantitative MRI Reveals the Elderly Ischemic Brain is Susceptible to Increased Early Blood—Brain Barrier Permeability Following Tissue Plasminogen Activator Related to Claudin 5 and Occludin Disassembly

Kaur

Tuor

Zhao

et al. 2011

J Cereb Blood Flow Metab

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“…All are based on the permanent [12,16,17] or transient occlusion of the middle cerebral artery (MCAO). Transient ischemia was accomplished for 30-120 min by means of a thrombus [18] , by intraluminal filament occlusion [15,19,20] or by means of a hook attached to a micromanipulator [11] . Long-term hypoxia-ischemia could also be induced by unilateral common carotid artery occlusion [21] .…”

Section: Stroke Models For Aged Ratsmentioning

confidence: 99%

“…Some studies in rats found that cerebral infarct in aged rats was the same size as in young [11,[16][17][18]23] , while others found that the older rats had larger infarct areas [19,20] .…”

Section: Aged Rats Have Higher Mortality Rates But Not Necessarily Lamentioning

confidence: 99%

Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

Petcu

Sfredel

Platt³

et al. 2007

Gerontology

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cells were rapidly incorporated into the glial scar, but these neuroepithelial-like cells did not make a significant contribution to neurogenesis in the infarcted cortex in young or aged animals. The response of plasticity-associated proteins like MAP1B, was delayed in aged rats. Tissue recovery was further delayed by an age-related increase in the amount of the neurotoxic C-terminal fragment of the ␤ -amyloid precursor protein (A-␤ ) at 2 weeks poststroke. Conclusion: The available evidence indicates that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis for this phenomenon in the aging brain could yield novel approaches to neurorestoration in the elderly.

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“…Further studies may use more advanced diffusion MRI techniques to better characterize neural tissue alterations within the complex pathophysiological environment along the injured visual pathways. [47][48][49][64][65][66] Future studies also may combine the developed imaging techniques here with functional MRI 36,67-70 and proton MR spectroscopy of the visual brain nuclei [71][72][73][74] for more in-depth monitoring of the structural-metabolic-functional relationships and the progression of HI in the visual system.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Neonatal Hypoxia-Ischemia on Structural and Physiological Integrity of the Eye and Visual Pathway by Multimodal MRI

Chan

Kancherla

Fan

et al. 2014

Investigative Ophthalmology & Visual Science

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Regional changes in the metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: A quantitative proton MRS study

Cited by 36 publications

References 33 publications

Quantitative MRI Reveals the Elderly Ischemic Brain is Susceptible to Increased Early Blood—Brain Barrier Permeability Following Tissue Plasminogen Activator Related to Claudin 5 and Occludin Disassembly

Quantitative MRI Reveals the Elderly Ischemic Brain is Susceptible to Increased Early Blood—Brain Barrier Permeability Following Tissue Plasminogen Activator Related to Claudin 5 and Occludin Disassembly

Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

Long-Term Effects of Neonatal Hypoxia-Ischemia on Structural and Physiological Integrity of the Eye and Visual Pathway by Multimodal MRI

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