2024 |
Sorby-Adams AJ, Marian OC, Bilecki IM, Elms LE, Yassi N, Hood RJ, et al., 'NK1 tachykinin receptor antagonist treatment reduces cerebral edema and intracranial pressure in an ovine model of ischemic stroke', Journal of Cerebral Blood Flow and Metabolism, (2024)
Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intrac... [more]
Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo). Anesthetized sheep (n = 24) were subject to 2-hours tMCAo and randomized (n = 6/group) to receive early NK1-R treatment (days 1¿3 post-stroke), delayed NK1-R treatment (day 5 post-stroke), or saline vehicle. At 6-days post-stroke animals were re-anaesthetized and ICP measured, followed by MRI to evaluate infarction, edema and BBB dysfunction. Following both early and delayed NK1-R antagonist administration, ICP was significantly reduced on day 6 compared to vehicle animals (p < 0.05), accompanied by a reduction in cerebral edema, midline shift and BBB dysfunction (p < 0.05). This study demonstrates that NK1-R antagonist treatment is an effective novel therapy for cerebral edema and elevated ICP following stroke in an ovine model, warranting future clinical evaluation.
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2023 |
Hood RJ, Beard DJ, McLeod DD, Murtha LA, Spratt NJ, 'Intracranial pressure elevation post-stroke: Mechanisms and consequences', Frontiers in Stroke, 2 [C1]
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Nova |
2023 |
Hood RJ, Sanchez-Bezanilla S, Beard DJ, Rust R, Turner RJ, Stuckey SM, et al., 'Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke', Journal of Neurochemistry, 167 733-752 (2023) [C1]
We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes... [more]
We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid-ß accumulation in the hippocampus, a region remote from the primary infarct. Interestingly, there is emerging evidence suggesting that deposition of amyloid-ß around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood¿brain barrier integrity. However, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the current study, we aimed to characterise the spatiotemporal cerebrovascular changes after cortical stroke. This was done using the photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Cerebrovascular morphology as well as the co-localisation of amyloid-ß with vasculature and blood¿brain barrier integrity were assessed in the cortex and hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed transient cerebrovascular remodelling in the peri-infarct area up to 28 days post-stroke. Importantly, the cerebrovascular changes were extended beyond the peri-infarct region to the ipsilateral hippocampus and were sustained out to 84 days post-stroke. When investigating vessel diameter, we showed a decrease at 84 days in the peri-infarct and CA1 regions that were exacerbated in vessels with amyloid-ß deposition. Lastly, we showed sustained vascular leakage in the peri-infarct and ipsilateral hippocampus, indicative of a compromised blood¿brain-barrier. Our findings indicate that hippocampal vasculature may represent an important therapeutic target to mitigate the progression of post-stroke cognitive impairment.
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Nova |
2023 |
Paul M, Paul JW, Hinwood M, Hood RJ, Martin K, Abdolhoseini M, et al., 'Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice', International Journal of Molecular Sciences, 24 11706-11706 [C1]
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Nova |
2023 |
Warren KE, Coupland KG, Hood RJ, Kang L, Walker FR, Spratt NJ, 'Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice', Fluids and Barriers of the CNS, 20 (2023) [C1]
Background: Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24... [more]
Background: Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24¿h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24¿h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation. Methods: Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24¿h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues. Results: At 24¿h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke. Conclusions: Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24¿h after stroke. This may contribute to reported increases in intracranial pressure at 24¿h after stroke and thus worsen stroke outcomes.
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Nova |
2023 |
Woods AG, Lillicrap T, Hood R, Fletcher JW, Ranhage V, Larsson E, et al., 'Blood Pressure Variability Is Associated with Infarct Growth in Acute Ischaemic Stroke', Cerebrovascular Diseases, (2023) [C1]
Introduction: Evidence-based blood pressure (BP) targets in acute ischaemic stroke are lacking. Previous observational studies have focused on single baseline BP and clinical outc... [more]
Introduction: Evidence-based blood pressure (BP) targets in acute ischaemic stroke are lacking. Previous observational studies have focused on single baseline BP and clinical outcomes, without consideration for dynamic changes. We aim to determine the association between BP parameters including variability, peak, nadir, median and mean during stroke and infarct growth (primary outcome), risk of haemorrhagic transformation, and functional outcome (secondary outcomes). Methods: Suspected stroke patients were prospectively recruited from a single comprehensive stroke centre. Multimodal computed tomography imaging was used to define infarct core. BP was recorded as per national stroke guidelines during the initial 24 h. Infarct growth and evidence of parenchymal haemorrhage were determined by follow-up magnetic resonance imaging at 24 h. Functional outcome at 3 months was assessed using the modified Rankin Scale. Subgroup analysis was performed according to stroke aetiology and treatment for the association between BP, infarct volume growth, and risk of haemorrhagic transformation. The association between BP parameters and outcomes were determined using regression modelling. Results: A total of 229 patients were included in this study. The median age was 67.4, 64.4% were male, and the baseline National Institutes of Health Stroke Scale was 8. BP variability (BPV) was independently associated with increased infarct growth (multivariate coefficient 1.60, 95% CI: 0.27¿2.94, p = 0.19) and an increased odds of parenchymal haemorrhage (adjusted OR 1.21, 95% CI: 1.02¿1.44, p = 0.028). The odds of a favourable outcome at 90 days were inversely associated with BPV on simple, but not adjusted logistic regression. On subgroup analysis, only in patients with large vessel occlusions, undergoing endovascular clot retrieval, was BPV associated with infarct growth (multivariate-adjusted coefficient 2.62, 95% CI: 0.53¿4.70, p = 0.014) and an increased odds of haemorrhagic transformation (adjusted OR 1.26, 95% CI: 1.01¿1.57, p = 0.045). Conclusion: An increase in BPV was associated with infarct expansion, increased risk of haemorrhagic transformation and was negatively associated with favourable functional outcomes at 3 months.
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2023 |
Kuhne C, Kecelioglu ED, Maltby S, Hood RJ, Knott B, Ditton E, et al., 'Direct comparison of virtual reality and 2D delivery on sense of presence, emotional and physiological outcome measures', Frontiers in Virtual Reality, 4 (2023) [C1]
Introduction: Virtual-reality (VR) technology has, over the last decade, quickly expanded from gaming into other sectors including training, education, and wellness. One of the mo... [more]
Introduction: Virtual-reality (VR) technology has, over the last decade, quickly expanded from gaming into other sectors including training, education, and wellness. One of the most popular justifications for the use of VR over 2D is increased immersion and engagement. However, very little fundamental research has been produced evaluating the comparative impact of immersive VR on the user¿s cognitive, physiological, and emotional state. Methods: A within-subject cross-over study design was used to directly compare VR and 2D screen delivery of different subject matter content. Both physiological and self-report data were collected for scenes containing calming nature environments, aggressive social confrontations, and neutral content. Results: Compared to 2D, the VR delivery resulted in a higher sense of presence, higher ratings of engagement, fun, and privacy. Confrontational scenes were rated as more tense whilst calming scenes were rated as more relaxing when presented in VR compared to 2D. Physiological data indicated that the scenes promoted overall states of arousal and relaxation in accordance with the scene subject matter (both VR and 2D). However, heart rate (HR) and galvanic skin response (GSR) were consistently higher throughout the VR delivery condition compared to 2D, including responses during scenes of neutral and calming subject matter. Discussion: This discrepancy between emotional and physiological responses for calming and neutral content in VR suggest an elevated arousal response driven by VR immersion that is independent of the emotional and physiological responses to the subject matter itself. These findings have important implications for those looking to develop and utilize VR technology as a training and educational tool as they provide insights into the impact of immersion on the user.
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Nova |
2022 |
Sanchez-Bezanilla S, Beard DJ, Hood RJ, Åberg ND, Crock P, Walker FR, et al., 'Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice.', Neural plasticity, 2022 9983042 (2022) [C1]
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Nova |
2022 |
Ryan A, Paul CL, Cox M, Whalen O, Bivard A, Attia J, et al., 'TACTICS-Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship: evaluating the effectiveness of an 'implementation intervention' in providing better patient access to reperfusion therapies: protocol for a non-randomised controlled stepped wedge cluster trial in acute stroke', BMJ OPEN, 12 (2022)
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2021 |
Zalewska K, Hood RJ, Pietrogrande G, Sanchez-Bezanilla S, Ong LK, Johnson SJ, et al., 'Corticosterone administration alters white matter tract structure and reduces gliosis in the sub-acute phase of experimental stroke', International Journal of Molecular Sciences, 22 (2021) [C1]
White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been... [more]
White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been suggested to be an independent predictor of post-stroke recovery. However, the factors that influence WMT remodeling are poorly understood. Cortisol is a steroid hormone released in response to prolonged stress, and elevated levels of cortisol have been reported to interfere with brain recovery. The objective of this study was to investigate the influence of corticosterone (CORT; the rodent equivalent of cortisol) on WMT structure post-stroke. Photothrombotic stroke (or sham surgery) was induced in 8-week-old male C57BL/6 mice. At 72 h, mice were exposed to standard drinking water ± CORT (100 µg/mL). After two weeks of CORT administration, mice were euthanised and brain tissue collected for histological and biochemical analysis of WMT (particularly the corpus cal-losum and corticospinal tract). CORT administration was associated with increased tissue loss within the ipsilateral hemisphere, and modest and inconsistent WMT reorganization. Further, a structural and molecular analysis of the WMT components suggested that CORT exerted effects over axons and glial cells. Our findings highlight that CORT at stress-like levels can moderately influence the reorganization and microstructure of WMT post-stroke.
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Nova |
2021 |
Hood RJ, Maltby S, Keynes A, Kluge MG, Nalivaiko E, Ryan A, et al., 'Development and Pilot Implementation of TACTICS VR: A Virtual Reality-Based Stroke Management Workflow Training Application and Training Framework', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Sanchez-Bezanilla S, Hood RJ, Collins-Praino LE, Turner RJ, Walker FR, Nilsson M, Ong LK, 'More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke', Journal of Cerebral Blood Flow and Metabolism, 41 2439-2455 (2021) [C1]
There is emerging evidence suggesting that a cortical stroke can cause delayed and remote hippocampal dysregulation, leading to cognitive impairment. In this study, we aimed to in... [more]
There is emerging evidence suggesting that a cortical stroke can cause delayed and remote hippocampal dysregulation, leading to cognitive impairment. In this study, we aimed to investigate motor and cognitive outcomes after experimental stroke, and their association with secondary neurodegenerative processes. Specifically, we used a photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Motor function was assessed using the cylinder and grid walk tasks. Changes in cognition were assessed using a mouse touchscreen platform. Neuronal loss, gliosis and amyloid-ß accumulation were investigated in the peri-infarct and ipsilateral hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed persistent impairment in cognitive function post-stroke, whilst there was a modest spontaneous motor recovery over the investigated period of 84 days. In the peri-infarct region, we detected a reduction in neuronal loss and decreased neuroinflammation over time post-stroke, which potentially explains the spontaneous motor recovery. Conversely, we observed persistent neuronal loss together with concomitant increased neuroinflammation and amyloid-ß accumulation in the hippocampus, which likely accounts for the persistent cognitive dysfunction. Our findings indicate that cortical stroke induces secondary neurodegenerative processes in the hippocampus, a region remote from the primary infarct, potentially contributing to the progression of post-stroke cognitive impairment.
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Nova |
2021 |
Hair K, Sena ES, Wilson E, Currie G, Macleod M, Bahor Z, et al., 'Building a Systematic Online Living Evidence Summary of COVID-19 Research', Journal of EAHIL, 17 21-26 (2021) [C1]
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Nova |
2021 |
Zhao Z, Hood RJ, Ong LK, Pietrogrande G, Sanchez Bezanilla S, Warren KE, et al., 'Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Bothwell SW, Omileke D, Hood RJ, Pepperall D-G, Azarpeykan S, Patabendige A, Spratt NJ, 'Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia', FRONTIERS IN MOLECULAR NEUROSCIENCE, 14 (2021) [C1]
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Nova |
2019 |
Patabendige A, MacKovski N, Pepperall D, Hood R, Spratt N, 'A26 Cerebrospinal fluid outflow resistance is increased following small-moderate ischaemic stroke (vol 16, 16, 2019)', FLUIDS AND BARRIERS OF THE CNS, 16 (2019)
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2018 |
Tan KN, Hood R, Warren K, Pepperall D, Carrasco-Pozo C, Manzanero S, et al., 'Heptanoate is neuroprotective in vitro but triheptanoin post-treatment did not protect against middle cerebral artery occlusion in rats', Neuroscience Letters, 683 207-214 (2018) [C1]
Triheptanoin, the medium-chain triglyceride of heptanoate, has been shown to be anticonvulsant and neuroprotective in several neurological disorders. In the gastrointestinal tract... [more]
Triheptanoin, the medium-chain triglyceride of heptanoate, has been shown to be anticonvulsant and neuroprotective in several neurological disorders. In the gastrointestinal tract, triheptanoin is cleaved to heptanoate, which is then taken up by the blood and most tissues, including liver, heart and brain. Here we evaluated the neuroprotective effects of heptanoate and its effects on mitochondrial oxygen consumption in vitro. We also investigated the neuroprotective effects of triheptanoin compared to long-chain triglycerides when administered after stroke onset in rats. Heptanoate pre-treatment protected cultured neurons against cell death induced by oxygen glucose deprivation and N-methyl-D-aspartate. Incubation of cultured astrocytes with heptanoate for 2 h increased mitochondrial proton leak and also enhanced basal respiration and ATP turnover, suggesting that heptanoate protects against oxidative stress and is used as fuel. However, continuous 72 h infusion of triheptanoin initiated 1 h after middle cerebral artery occlusion in rats did not alter stroke volume at 3 days or neurological deficit at 1 and 3 days relative to long-chain triglyceride control treatment.
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Nova |
2016 |
Beard DJ, Logan CL, McLeod DD, Hood RJ, Pepperall D, Murtha LA, Spratt NJ, 'Ischemic penumbra as a trigger for intracranial pressure rise - A potential cause for collateral failure and infarct progression?', J Cereb Blood Flow Metab, 36 917-927 (2016) [C1]
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Nova |
2016 |
Tomkins AJ, Hood RJ, Pepperall D, Null CL, Levi CR, Spratt NJ, 'Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis.', J Am Heart Assoc, 5 (2016) [C1]
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Nova |
2015 |
Mcleod DD, Parsons MW, Hood R, Hiles B, Allen J, Mccann SK, et al., 'Perfusion computed tomography thresholds defining ischemic penumbra and infarct core: Studies in a rat stroke model', International Journal of Stroke, 10 553-559 (2015) [C1]
Background: Perfusion computed tomography is becoming more widely used as a clinical imaging tool to predict potentially salvageable tissue (ischemic penumbra) after ischemic stro... [more]
Background: Perfusion computed tomography is becoming more widely used as a clinical imaging tool to predict potentially salvageable tissue (ischemic penumbra) after ischemic stroke and guide reperfusion therapies. Aims: The study aims to determine whether there are important changes in perfusion computed tomography thresholds defining ischemic penumbra and infarct core over time following stroke. Methods: Permanent middle cerebral artery occlusion was performed in adult outbred Wistar rats (n=6) and serial perfusion computed tomography scans were taken every 30 mins for 2h. To define infarction thresholds at 1h and 2h post-stroke, separate groups of rats underwent 1h (n=6) and 2h (n=6) of middle cerebral artery occlusion followed by reperfusion. Infarct volumes were defined by histology at 24h. Co-registration with perfusion computed tomography maps (cerebral blood flow, cerebral blood volume, and mean transit time) permitted pixel-based analysis of thresholds defining infarction, using receiver operating characteristic curves. Results: Relative cerebral blood flow was the perfusion computed tomography parameter that most accurately predicted penumbra (area under the curve=0·698) and also infarct core (area under the curve=0·750). A relative cerebral blood flow threshold of <75% of mean contralateral cerebral blood flow most accurately predicted penumbral tissue at 0·5h (area under the curve=0·660), 1h (area under the curve=0·659), 1·5h (area under the curve=0·636), and 2h (area under the curve=0·664) after stroke onset. A relative cerebral blood flow threshold of <55% of mean contralateral most accurately predicted infarct core at 1h (area under the curve=0·765) and at 2h (area under the curve=0·689) after middle cerebral artery occlusion. Conclusions: The data provide perfusion computed tomography defined relative cerebral blood flow thresholds for infarct core and ischemic penumbra within the first two hours after experimental stroke in rats. These thresholds were shown to be stable to define the volume of infarct core and penumbra within this time window.
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Nova |
2015 |
Tomkins AJ, Hood RJ, Levi CR, Spratt NJ, 'Tissue Plasminogen Activator for preclinical stroke research: Neither "rat" nor "human" dose mimics clinical recanalization in a carotid occlusion model', SCIENTIFIC REPORTS, 5 (2015) [C1]
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Nova |