6 results on '"Wehn, Antonia Clarissa"'
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2. RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury
- Author
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Wehn, Antonia Clarissa, Khalin, Igor, Duering, Marco, Hellal, Farida, Culmsee, Carsten, Vandenabeele, Peter, Plesnila, Nikolaus, and Terpolilli, Nicole Angela
- Published
- 2021
- Full Text
- View/download PDF
3. Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo.
- Author
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Shrouder, Joshua James, Calandra, Gian Marco, Filser, Severin, Varga, Daniel Peter, Besson-Girard, Simon, Mamrak, Uta, Dorok, Maximilian, Bulut-Impraim, Buket, Seker, Fatma Burcu, Gesierich, Benno, Laredo, Fabio, Wehn, Antonia Clarissa, Khalin, Igor, Bayer, Patrick, Liesz, Arthur, Gokce, Ozgun, and Plesnila, Nikolaus
- Subjects
PERICYTES ,ISCHEMIC stroke ,BLOOD flow ,CAPILLARIES ,REPERFUSION - Abstract
Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged. Moreover, we revealed ischaemic pericytes to be fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 h post stroke. Despite sustaining acute membrane damage, we observed that over half of all cortical pericytes survived ischaemia and responded to vasoactive stimuli, upregulated unique transcriptomic profiles and replicated. Finally, we demonstrated the delayed recovery of capillary diameter by ischaemic pericytes after reperfusion predicted vessel reconstriction in the subacute phase of stroke. Cumulatively, these findings demonstrate that surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischaemic stroke. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Additional file 1 of RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury
- Author
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Wehn, Antonia Clarissa, Khalin, Igor, Duering, Marco, Hellal, Farida, Culmsee, Carsten, Vandenabeele, Peter, Plesnila, Nikolaus, and Terpolilli, Nicole Angela
- Abstract
Additional File 1 Supplementary Fig. S1. Genotyping of RIPK1 and RIPK3 deficient mice and proof of neuronal specific RIPK1 knock-out in RIPK1flox/floxCamk2CreERT2 mice. a. Neuron specific RIPK1 deficient mice used for experiments were heterozygous for Camk2CreERT2 and homozygous for the floxed RIPK1 allele. Littermate controls were also homozygous for the floxed RIPK1 allele, but did not express the Cre recombinase. b. Global RIPK3 deficient mice were homozygous for disrupted allele, while control mice expressed only the wild type gene. c. and d. To demonstrate specific neuron specific RIPK1 deficiency in induced RIPK1flox/floxCamk2CreERT2 mice, we performed immunohistochemistry for RIPK1 and NeuN, a neuronal marker. In the cortex of control mice RIPK1 was almost exclusively expressed in neurons (upper panels), while in induced RIPK1flox/floxCamk2CreERT2 mice RIPK1 staining was significantly reduced (lower panels) to 20% of baseline (d). Additional File 1 Supplementary Fig. 2 Body weight and physical condition after experimental TBI. a. and b. Weight after TBI. Animals recovered from weight loss directly after trauma within one week after injury; in the following observation period weight constantly increased. No differences were detected between CCI and sham-operated animals in the RIPK1 (a) and RIPK3 (b) groups. c. and d. General health score to assess recovery. All animals��� general condition transiently worsened in the perioperative phase with a peak at day 1 after TBI, but returned to baseline within one week. There was no difference between groups, c. RIPK1, d. RIPK3. Data are presented as mean �� SD; n = 5 for sham, n = 8���10 for TBI. Additional File 1 Supplementary Fig. 3. Individual lesion volume progression for a. RIP1 and b. RIP3 deficient mice. Additional File 1 Supplementary Fig. 4. RIPK3 deficiency does not affect acute brain injury after TBI. No differences in lesion volume as assessed by histology was detected between RIPK3 knockout mice and C57BL/6 wild type controls at 24 h after TBI. Data are presented as mean �� SD; n = 10. Additional File 1 Supplementary Fig. 5. Lesion volumes by MRI and histology. a. T2-weighted MRI and Nissl stained coronal section three months after injury. Lesion volume was quantified in T2-weighted MRI images as well as Nissl stained sections obtained in the same animals three months post injury. b. Correlation analysis of lesion volumes assessed by histomorphometry or T2-weighted MRI revealed a strong positive correlation between both methods. Differences in measured lesion size are due to shrinking of tissue in the fixation process, with a shrinking factor of 0.77 �� 0.23. c.���f. Quantification of lesion volume (c. RIPK1, d. RIPK3) as well as hippocampal damage (e. RIPK1, f. RIPK3) using both methods. Data are presented as mean �� SD; n = 8���10 for TBI. Pearson correlation, Students t-test for parametric and Man-Whitney-Rank-Sum test for non-parametric data were used. *p
- Published
- 2021
- Full Text
- View/download PDF
5. Bradykinin 2 Receptors Mediate Long-Term Neurocognitive Deficits After Experimental Traumatic Brain Injury.
- Author
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Wehn AC, Khalin I, Hu S, Harapan BN, Mao X, Cheng S, Plesnila N, and Terpolilli NA
- Abstract
The kallikrein-kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of bradykinin 2 receptors (B2R). However, the influence of B2R on chronic post-traumatic damage and outcome is unclear. In the current study, we assessed long-term effects of B2R-knockout (KO) after experimental TBI. B2R KO mice (heterozygous, homozygous) and wild-type (WT) littermates ( n = 10/group) were subjected to controlled cortical impact (CCI) TBI. Lesion size was evaluated by magnetic resonance imaging up to 90 days after CCI. Motor and memory function were regularly assessed by Neurological Severity Score, Beam Walk, and Barnes maze test. Ninety days after TBI, brains were harvested for immunohistochemical analysis. There was no difference in cortical lesion size between B2R-deficient and WT animals 3 months after injury; however, hippocampal damage was reduced in B2R KO mice ( p = 0.03). Protection of hippocampal tissue was accompanied by a significant improvement of learning and memory function 3 months after TBI ( p = 0.02 WT vs. KO), whereas motor function was not influenced. Scar formation and astrogliosis were unaffected, but B2R deficiency led to a gene-dose-dependent attenuation of microglial activation and a reduction of CD45+ cells 3 months after TBI in cortex ( p = 0.0003) and hippocampus ( p < 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment are mediated by prolonged neuroinflammation and B2R. Inhibition of B2R may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.
- Published
- 2024
- Full Text
- View/download PDF
6. Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo.
- Author
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Shrouder JJ, Calandra GM, Filser S, Varga DP, Besson-Girard S, Mamrak U, Dorok M, Bulut-Impraim B, Seker FB, Gesierich B, Laredo F, Wehn AC, Khalin I, Bayer P, Liesz A, Gokce O, and Plesnila N
- Subjects
- Humans, Pericytes physiology, Cerebral Infarction, Stroke, Brain Ischemia, Ischemic Stroke
- Abstract
Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged. Moreover, we revealed ischaemic pericytes to be fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 h post stroke. Despite sustaining acute membrane damage, we observed that over half of all cortical pericytes survived ischaemia and responded to vasoactive stimuli, upregulated unique transcriptomic profiles and replicated. Finally, we demonstrated the delayed recovery of capillary diameter by ischaemic pericytes after reperfusion predicted vessel reconstriction in the subacute phase of stroke. Cumulatively, these findings demonstrate that surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischaemic stroke., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
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