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Fulltext Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging

Harston GW, Tee YK, Blockley N, Okell TW, Thandeswaran S, Shaya G, et al.

Brain, 2015 Jan;138(Pt 1):36-42.
PMID: 25564491 DOI: 10.1093/brain/awu374

The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.

Matched MeSH terms: Cerebrovascular Circulation/physiology*
Changes in blood-brain barrier permeability and ultrastructure, and protein expression in a rat model of cerebral hypoperfusion

Sekaran H, Gan CY, A Latiff A, Harvey TM, Mohd Nazri L, Hanapi NA, et al.

Brain Res Bull, 2019 10;152:63-73.
PMID: 31301381 DOI: 10.1016/j.brainresbull.2019.07.010

Cerebral hypoperfusion involved a reduction in cerebral blood flow, leading to neuronal dysfunction, microglial activation and white matter degeneration. The effects on the blood-brain barrier (BBB) however, have not been well-documented. Here, two-vessel occlusion model was adopted to mimic the condition of cerebral hypoperfusion in Sprague-Dawley rats. The BBB permeability to high and low molecular weight exogenous tracers i.e. Evans blue dye and sodium fluorescein respectively, showed marked extravasation of the Evans blue dye in the frontal cortex, posterior cortex and thalamus-midbrain at day 1 following induction of cerebral hypoperfusion. Transmission electron microscopy revealed brain endothelial cell and astrocyte damages including increased pinocytotic vesicles and formation of membrane invaginations in the endothelial cells, and swelling of the astrocytes' end-feet. Investigation on brain microvessel protein expressions using two-dimensional (2D) gel electrophoresis coupled with LC-MS/MS showed that proteins involved in mitochondrial energy metabolism, transcription regulation, cytoskeleton maintenance and signaling pathways were differently expressed. The expression of aconitate hydratase, heterogeneous nuclear ribonucleoprotein, enoyl Co-A hydratase and beta-synuclein were downregulated, while the opposite observed for calreticulin and enhancer of rudimentary homolog. These findings provide insights into the BBB molecular responses to cerebral hypoperfusion, which may assist development of future therapeutic strategies.

Matched MeSH terms: Cerebrovascular Circulation/physiology*
Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion

Azzubaidi MS, Saxena AK, Talib NA, Ahmed QU, Dogarai BB

Acta Neurobiol Exp (Wars), 2012;72(2):154-65.
PMID: 22810217

The fixed oil of black cumin seeds, Nigella sativa L. (NSO), has shown considerable antioxidant and anti-inflammatory activities. Chronic cerebral hypoperfusion has been linked to neurodegenerative disorders including Alzheimer's disease (AD) and its subsequent cognitive impairment in which oxidative stress and neuroinflammation are the principal culprits. Cerebrovascular hypoperfusion was experimentally achieved by bilateral common carotid arteries occlusion (2VO) in rats. Morris water maze (MWM) test was employed to assess the effects of NSO on spatial cognitive function before and after 2VO intervention. Rats were divided into long-term memory (LTM) and short-term memory (STM) groups, each was further subdivided into 3 subgroups: sham control, untreated 2VO and NSO treated 2VO group. All subgroups were tested with MWM at the tenth postoperative week. Working memory test results for both sham control and NSO treated groups showed significantly lower escape latency time and total distance travelled than untreated 2VO group. Similarly, LTM and STM MWM tests for sham control and NSO treated groups revealed significantly better maze test performance as compared to untreated 2VO group. Sham control and NSO treated 2VO groups demonstrated superior probe memory test performance as compared to untreated 2VO group. The fixed oil of Nigella sativa seeds has demonstrated noticeable spatial cognitive preservation in rats challenged with chronic cerebral hypoperfusion which indicates a promising prospective neuroprotective effect.

Matched MeSH terms: Cerebrovascular Circulation/physiology
The nootropic and anticholinesterase activities of Clitoria ternatea Linn. root extract: Potential treatment for cognitive decline

Damodaran T, Cheah PS, Murugaiyah V, Hassan Z

Neurochem Int, 2020 10;139:104785.
PMID: 32650028 DOI: 10.1016/j.neuint.2020.104785

BACKGROUND: Clitoria ternatea (CT) is an herbal plant that has been used as a memory booster in folk medicine. CT root extract has been proven to restore chronic cerebral hypoperfusion (CCH)-induced memory deficits in a rat model, but the underlying mechanisms and the toxicity profile following repeated exposure have yet to be explored.
THE AIM OF THE STUDY: To investigate the effects of the chronic (28 days) oral administration of CT root extract on CCH-induced cognitive impairment, neuronal damage and cholinergic deficit, and its toxicity profile in the CCH rat model.
MATERIALS AND METHODS: The permanent bilateral occlusion of common carotid arteries (PBOCCA) surgery method was employed to develop a CCH model in male Sprague Dawley (SD) rats. Then, these rats were given oral administration of CT root extract at doses of 100, 200, and 300 mg/kg, respectively for 28 days and subjected to behavioural tests. At the end of the experiment, the brain was harvested for histological analysis and cholinesterase activities. Then, blood samples were collected and organs such as liver, kidney, lung, heart, and spleen were procured for toxicity assessment.
RESULTS: Chronic treatment of CT root extract at doses of 200 and 300 mg/kg, restored memory impairments induced by CCH. CT root extract was also found to diminish CCH-induced neuronal damage in the CA1 region of the hippocampus. High dose (300 mg/kg) of the CT root extract was significantly inhibited the increased acetylcholinesterase (AChE) activity in the frontal cortex and hippocampus of the PBOCCA rats. In toxicity study, repeated doses of CT root extract were found to be safe in PBOCCA rats after 28 days of treatment.
CONCLUSIONS: Our findings provided scientific evidence supporting the therapeutic potential of CT root extract in the treatment of vascular dementia (VaD)-related cholinergic abnormalities and subsequent cognitive decline.

Matched MeSH terms: Cerebrovascular Circulation/physiology