Intralesional Patterns of MRI ADC Maps Predict Outcome in Experimental Stroke

2015 ◽  
Vol 39 (5-6) ◽  
pp. 293-301 ◽  
Author(s):  
Isabel Lestro Henriques ◽  
María Gutiérrez-Fernández ◽  
Berta Rodríguez-Frutos ◽  
Jaime Ramos-Cejudo ◽  
Laura Otero-Ortega ◽  
...  
Keyword(s):  
Cell Death ◽  
Functional Outcome ◽  
Lesion Size ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Acute Ischemia ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Ischemic Tissue ◽  
Cerebral Artery Occlusion

Background: After acute ischemia, the tissue that is at risk of infarction can be detected by perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch but the time that is needed to process PWI limits its use. As DWI is highly sensitive to acute ischemic tissue damage, we hypothesized that different ADC patterns represent areas with a different potential for recovery. Methods: In a model of permanent middle cerebral artery occlusion (pMCAO), Sprague-Dawley rats were randomly distributed to sham surgery and pMCAO. We further separated the pMCAO group according to intralesional ADC pattern (homogeneous or heterogeneous). At 24 h after ischemia induction, we analyzed lesion size, functional outcome, cell death expression, and brain protection markers including ROS enzyme NOX-4. MRI included DWI (ADC maps), DTI (tractography), and PWI (CBF, CBV and MTT). Results: The lesion size was similar in pMCAO rats. Animals with a heterogeneous pattern in ADC maps showed better functional outcome in Rotarod test (p = 0.032), less expression of cell death (p = 0.014) and NOX-4 (p = 0.0063), higher intralesional CBF (p = 0.0026) and larger PWI/DWI mismatch (p = 0.007). Conclusions: In a rodent model for ischemic stroke, intralesional heterogeneity in ADC maps was related to better functional outcome in lesions of similar size and interval after pMCAO. DWI ADC maps may assist in the early identification of ischemic tissue with an increased potential for recovery as higher expression of acute protection markers, lower expression of cell death, increased PWI/DWI mismatch, and higher intralesional CBF were present in animals with a heterogeneous ADC pattern.

scholarly journals Spectacular Shrinking Deficit: Insights from Multimodal Magnetic Resonance Imaging after Embolic Middle Cerebral Artery Occlusion in Sprague—Dawley Rats

2007 ◽  
Vol 27 (10) ◽  
pp. 1756-1763 ◽  
Author(s):  
Nils Henninger ◽  
Kenneth M Sicard ◽  
Marc Fisher
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Functional Magnetic Resonance Imaging ◽  
Middle Cerebral Artery ◽  
Artery Occlusion ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cerebral Artery Occlusion

Almost no data is available on the serial changes in the brain after spectacular shrinking deficit (SSD) that may help understand this relatively rare clinical phenomenon. Quantitative diffusion-(DWI), perfusion-(PWI), T1-(T1WI), T2-weighted (T2WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 7 days after embolic middle cerebral artery occlusion (eMCAO) in male Sprague—Dawley rats ( n = 9). Region of interest (ROI) analysis was used to evaluate structural and functional MR signal changes within three ROIs defined by the apparent diffusion coefficient (ADC), cerebral blood flow (CBF) signatures, and final tissue viability. DWI, PWI, and T2WI lesion volumes were calculated using previously established viability thresholds and final infarct volumes ascertained with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Serial MRI demonstrated spontaneous reperfusion of initially hypoperfused MCA regions accompanied by substantial reduction of initial ADC and CBF lesions and gradual recovery of neurological outcome. Recovery rates of CBF/ADC abnormalities differed among ROIs. Functional magnetic resonance imaging showed persistent tissue dysfunction after the recovery of the CBF/ADC lesions. This study may facilitate our understanding of the pathophysiological mechanisms by which early, spontaneous reperfusion affects tissue fate and neurological function.

scholarly journals Effect of Photobiomodulation in Rescuing Lipopolysaccharide-Induced Dopaminergic Cell Loss in the Male Sprague–Dawley Rat

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 381 ◽  
Author(s):  
O’Brien ◽  
Austin
Keyword(s):  
Cell Death ◽  
Cell Loss ◽  
Lesion Size ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Dopaminergic Cell ◽  
Sprague Dawley Rats ◽  
Neuroprotective Therapy ◽  
Potential Benefits ◽  
Inflammatory Component

Photobiomodulation (PBM) provides neuroprotection against dopaminergic cell death and associated motor deficits in rodent and primate models of Parkinson’s disease (PD). However, it has not yet been tested in the lipopolysaccharide (LPS) model of PD, which leads to dopaminergic cell death through microglia-evoked neuroinflammation. We investigated whether transcranial PBM could protect against dopaminergic cell death within the substantia nigra in male Sprague–Dawley rats following supranigral LPS injection. PBM fully protected rats from 10 µg LPS which would have otherwise caused 15% cell loss, but there was no significant neuroprotection at a 20 µg dose that led to a 50% lesion. Cell loss at this dose varied according to the precise site of injection and correlated with increased local numbers of highly inflammatory amoeboid microglia. Twenty microgram LPS caused motor deficits in the cylinder, adjusted stepping and rotarod tests that correlated with dopaminergic cell loss. While PBM caused no significant improvement at the group level, motor performance on all three tests no longer correlated with the lesion size caused by 20 µg LPS in PBM-treated rats, suggesting extranigral motor improvements in some animals. These results provide support for PBM as a successful neuroprotective therapy against the inflammatory component of early PD, provided inflammation has not reached a devastating level, as well as potential benefits in other motor circuitries.

scholarly journals Progesterone Attenuates Hemorrhagic Transformation after Delayed tPA Treatment in an Experimental Model of Stroke in Rats: Involvement of the VEGF–MMP Pathway

2013 ◽  
Vol 34 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Soonmi Won ◽  
Jin Hwan Lee ◽  
Bushra Wali ◽  
Donald G Stein ◽  
Iqbal Sayeed
Keyword(s):  
Time Window ◽  
Culture Media ◽  
Hemorrhagic Transformation ◽  
Artery Occlusion ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Bbb Permeability ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for acute stroke, but its use remains limited. Progesterone (PROG) has shown neuroprotection in ischemia, but before clinical testing, we must determine how it affects hemorrhagic transformation in tPA-treated ischemic rats. Male Sprague–Dawley rats underwent middle cerebral artery occlusion with reperfusion at 4.5 hours and tPA treatment at 4.5 hours, or PROG treatment intraperitoneally at 2 hours followed by subcutaneous injection at 6 hours post occlusion. Rats were killed at 24 hours and brains evaluated for cerebral hemorrhage, swelling, blood–brain barrier (BBB) permeability, and levels of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor level (VEGF), and tight junction (TJ) proteins. We also evaluated PROG's efficacy in preventing tPA-induced impairment of transendothelial electrical resistance (TEER) and TJ proteins under hypoxia/reoxygenation in the endothelial cells. Delayed tPA treatment induced significant hemorrhagic conversion and brain swelling. Treatment with PROG plus tPA ameliorated hemorrhage, hemispheric swelling, BBB permeability, MMP-9 induction, and VEGF levels compared with controls. Progesterone treatment significantly prevented tPA-induced decrease in TEER and expression of occludin and claudin-5, and attenuated VEGF levels in culture media subjected to hypoxia. The study concluded that PROG may extend the time window for tPA administration in ischemic stroke and reduce hemorrhagic conversion.

scholarly journals Local Cerebral Glucose Utilization and Cytoskeletal Proteolysis as Indices of Evolving Focal Ischemic Injury in Core and Penumbra

1995 ◽  
Vol 15 (3) ◽  
pp. 398-408 ◽  
Author(s):  
Hiroshi Yao ◽  
Myron D. Ginsberg ◽  
David D. Eveleth ◽  
Joseph C. LaManna ◽  
Brant D. Watson ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Neutral Red ◽  
Artery Occlusion ◽  
Variable Degree ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Ischemic Core ◽  
Cerebral Artery Occlusion

To ascertain the tempo of progression to irreversible injury in focal ischemia, we subjected halothaneanesthetized Sprague–Dawley rats to photochemically induced distal middle cerebral artery occlusion (dMCAO) combined with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Head temperature was maintained at 36°C. At times centered at either 1.5 or 3 h post-dMCAO, the rate of local glucose metabolism (lCMRgl) was measured by 2-deoxyglucose autoradiography, and cytoskeletal proteolysis was assessed regionally by an immunoblotting procedure to detect spectrin breakdown products. At 1.5 h (n = 5), the cortical ischemic core was already severely hypometabolic (lCMRgl 15.5 ± 10.8 μmol 100 g−1 min−1, mean ± SD), whereas the cortical penumbral zone was hypermetabolic (69.0 ± 9.7). (The lumped constant was verified to be unchanged by methylglucose studies.) Neutral red pH studies at this time point showed that both the core and penumbral zones were equally acidotic. By 3 h post-dMCAO (n = 6), lCMRgl in the penumbral zone had fallen to low levels (15.4 ± 2.2 μmol 100 g−1 min−1) equal to those of the ischemic core (16.7 ± 4.5). Correspondingly, spectrin breakdown in the ischemic core was advanced at both 2 and 3.5 h post-dMCAO (36 ± 18% and 33 ± 18% of total spectrin, respectively), whereas in the penumbral zone spectrin breakdown was less extensive and more highly variable at both times (22 ± 23% and 29 ± 16%). We conclude that irreversible deterioration of the ischemic core, as evidenced by the onset of local cytoskeletal proteolysis, begins within 2 h of middle cerebral artery occlusion. In the ischemic penumbra, the transition from glucose hyper- to hypometabolism occurs by 3.5 h and is associated with a milder and more variable degree of spectrin breakdown.

scholarly journals Stroke Penumbra Defined by an MRI-Based Oxygen Challenge Technique: 1. Validation using [14C]2-Deoxyglucose Autoradiography

2011 ◽  
Vol 31 (8) ◽  
pp. 1778-1787 ◽  
Author(s):  
Craig A Robertson ◽  
Christopher McCabe ◽  
Lindsay Gallagher ◽  
Maria del Rosario Lopez-Gonzalez ◽  
William M Holmes ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Artery Occlusion ◽  
Magnetic Resonance Images ◽  
Sprague Dawley ◽  
Accurate Identification ◽  
Sprague Dawley Rats ◽  
Signal Change ◽  
Ischemic Core ◽  
Magnetic Resonance Imaging Mri ◽  
Cerebral Artery Occlusion

Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T*2 MRI (T*2 OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T*2 signal change during OC. [14C]2-deoxyglucose (2-DG) autoradiography was combined with T*2 OC to determine metabolic status of T*2-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats ( n = 6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T*2 signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T*2-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T*2 signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T*2 signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.

Inflammation-relevant microbiome signature of the stroke brain, gut, spleen, and thymus and the impact of exercise

2021 ◽  
pp. 0271678X2110395
Author(s):  
Chase Kingsbury ◽  
Alex Shear ◽  
Matt Heyck ◽  
Nadia Sadanandan ◽  
Henry Zhang ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Calcium Binding ◽  
Unmet Need ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Sprague Dawley Rats ◽  
Factor Alpha ◽  
Cerebral Artery Occlusion ◽  
The Impact

Stroke remains a significant unmet need in the clinic with few therapeutic options. We, and others, have implicated the role of inflammatory microbiota in stroke secondary cell death. Elucidating this inflammation microbiome as a biomarker may improve stroke diagnosis and treatment. Here, adult Sprague-Dawley rats performed 30 minutes of exercise on a motorized treadmill for 3 consecutive days prior to transient middle cerebral artery occlusion (MCAO). Stroke animals that underwent exercise showed 1) robust behavioral improvements, 2) significantly smaller infarct sizes and increased peri-infarct cell survival and 3) decreasing trends of inflammatory microbiota BAC303, EREC482, and LAB158 coupled with significantly reduced levels of inflammatory markers ionized calcium binding adaptor molecule 1, tumor necrosis factor alpha, and mouse monoclonal MHC Class II RT1B in the brain, gut, spleen, and thymus compared to non-exercised stroke rats. These results suggest that a specific set of inflammatory microbiota exists in central and peripheral organs and can serve as a disease biomarker and a therapeutic target for stroke.

Sign in / Sign up

Export Citation Format

Share Document