Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · May 2014
Clinical TrialRegional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride.
Individuals with high-level spinal cord injury (SCI) experience low blood pressure (BP) and cognitive impairments. Such dysfunction may be mediated in part by impaired neurovascular coupling (NVC) (i.e., cerebral blood flow responses to neurologic demand). Ten individuals with SCI >T6 spinal segment, and 10 age- and sex-matched controls were assessed for beat-by-beat BP, as well as middle and posterior cerebral artery blood flow velocity (MCAv, PCAv) in response to a NVC test. ⋯ When BP was increased with midodrine, NVC was improved 70% in SCI, which was reflected by a 13% improved cognitive function (P<0.05). Improvements in BP were related to improved cognitive function in those with SCI (r(2)=0.52; P<0.05). Impaired NVC, secondary to low BP, may partially mediate reduced cognitive function in individuals with high-level SCI.
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J. Cereb. Blood Flow Metab. · May 2014
Diagnostic utility of amyloid PET in cerebral amyloid angiopathy-related symptomatic intracerebral hemorrhage.
By detecting β-amyloid (Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (l-ICH). No previous study has directly assessed the diagnostic value of (11)C-Pittsburgh compound B (PiB) PET in probable CAA-related l-ICH against healthy controls (HCs). (11)C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic l-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. ⋯ Similar but less accurate results were found using visual analysis. In patients with sl-ICH, (11)C-PiB-PET has low specificity for CAA due to the frequent occurrence of high (11)C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials.
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J. Cereb. Blood Flow Metab. · Apr 2014
Altered functional organization within and between resting-state networks in chronic subcortical infarction.
This study aimed to investigate the changes in functional connectivity (FC) within each resting-state network (RSN) and between RSNs in subcortical stroke patients who were well recovered in global motor function. Eleven meaningful RSNs were identified via functional magnetic resonance imaging data from 25 subcortical stroke patients and 22 normal controls using independent component analysis. ⋯ Stroke patients also exhibited weakened positive (anterior and posterior DMN; posterior DMN and right FPN) or negative (AN and right FPN; posterior DMN and dorsal SMN) internetwork FC when compared with normal controls. We suggest that subcortical stroke may induce connectivity changes in multiple functional networks, affecting not only the intranetwork FC within RSNs but also the internetwork FC between these RSNs.
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J. Cereb. Blood Flow Metab. · Apr 2014
PPAR agonist-mediated protection against HIV Tat-induced cerebrovascular toxicity is enhanced in MMP-9-deficient mice.
The strategies to protect against the disrupted blood-brain barrier (BBB) in HIV-1 infection are not well developed. Therefore, we investigated the potential of peroxisome proliferator-activated receptor (PPAR) agonists to prevent enhanced BBB permeability induced by HIV-1-specific protein Tat. Exposure to Tat via the internal carotid artery (ICA) disrupted permeability across the BBB; however, this effect was attenuated in mice treated with fenofibrate (PPARα agonist) or rosiglitazone (PPARγ agonist). ⋯ Because disruption of TJ integrity has been linked to matrix metalloproteinase (MMP) activity, we also evaluated Tat-induced effects in MMP-9-deficient mice. Tat-induced cerebrovascular toxicity, astrogliosis, and neuronal loss were less pronounced in MMP-9-deficient mice as compared with wild-type controls and were further attenuated by PPAR agonists. These results indicate that enhancing PPAR activity combined with targeting MMPs may provide effective therapeutic strategies in brain infection by HIV-1.
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J. Cereb. Blood Flow Metab. · Apr 2014
NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke.
Although the innate immune response to induce postischemic inflammation is considered as an essential step in the progression of cerebral ischemia injury, the role of innate immunity mediator NLRP3 in the pathogenesis of ischemic stroke is unknown. In this study, focal ischemia was induced by middle cerebral artery occlusion in NLRP3(-/-), NOX2(-/-), or wild-type (WT) mice. By magnetic resonance imaging (MRI), Evans blue permeability, and electron microscopic analyses, we found that NLRP3 deficiency ameliorated cerebral injury in mice after ischemic stroke by reducing infarcts and blood-brain barrier (BBB) damage. ⋯ Finally, we found that NOX2 deficiency improved outcomes after ischemic stroke by mediating NLRP3 signaling. This study for the first time shows the contribution of NLRP3 to neurovascular damage and provides direct evidence that NLRP3 as an important target molecule links NOX2-mediated oxidative stress to neurovascular damage in ischemic stroke. Pharmacological targeting of NLRP3-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.