رسالة جامعية
Neuronal tPA : implications for the modulation of perineuonal nets and the pathophysiology of ischemic stroke ; Activateur tissulaire du plasminogène (tPA) neuronal : implications dans la modulation des réseaux perineuronaux (PNNs) et la physiopathologie des accidents vasculaires cérébraux (AVC) ischémiques
| العنوان: | Neuronal tPA : implications for the modulation of perineuonal nets and the pathophysiology of ischemic stroke ; Activateur tissulaire du plasminogène (tPA) neuronal : implications dans la modulation des réseaux perineuronaux (PNNs) et la physiopathologie des accidents vasculaires cérébraux (AVC) ischémiques |
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| المؤلفون: | Prunotto, Paul |
| المساهمون: | Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université, Carine Ali |
| المصدر: | https://theses.hal.science/tel-04326242Test ; Médecine humaine et pathologie. Normandie Université, 2023. Français. ⟨NNT : 2023NORMC417⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2023 |
| المجموعة: | Normandie Université: HAL |
| مصطلحات موضوعية: | Tissue plasminogen activator, Interneurons, Neurons, Excitotoxicity, Ischemic stroke, Perineuronal Nets, Réseaux périneuronaux, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | Tissue-type plasminogen activator (tPA) is primarily known for its role in fibrinolysis, converting plasminogen into active plasmin, a critical process in the dissolution of blood clots. This property makes its recombinant form the only pharmacological treatment for ischemic strokes. Strokes are characterized by a sudden interruption of blood supply to the brain, triggering a cascade of cellular responses, including excitotoxic cell death. However, tPA's role extends beyond vascular functions, as it also acts as a neuromodulator of glutamatergic transmission by interacting with NMDA receptors, influencing various neurobiological processes. This thesis pursued two main objectives. Firstly, it examined the role of tPA expressed by parvalbumin (PV) interneurons in the regulation of perineuronal nets (PNNs) under normal conditions and in post-ischemic functional recovery. Secondly, it explored the role of endogenous neuronal tPA in the acute phase of excitotoxicity and ischemia using innovative approaches based on Adeno-Associated Viruses (AAV). In the first study, the absence of tPA in PV interneurons led to a significant increase in PNN density in the somatosensory cortex, with tPA playing a crucial role in aggrecan degradation. Interestingly, mice deficient in tPA only in PV interneurons showed faster functional recovery after thromboembolic stroke, even though PNNs did not seem to play a direct role in this process. It was observed that tPA increased the activation of NMDA receptors on PV interneurons, suggesting a potential link with functional recovery. In the second study, we confirmed the presence of tPA within cortical neurons using AAV9-pPlat-GFP vectors. In an excitotoxic context, tPA-expressing neurons exhibited increased resistance compared to those without tPA, while also exerting a paracrine toxic effect on neighboring neurons lacking tPA. Furthermore, during thromboembolic ischemia, neuronal tPA deletion had deleterious effects, increasing ischemic lesion volumes and neuronal death, regardless of the ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | French |
| العلاقة: | NNT: 2023NORMC417; tel-04326242; https://theses.hal.science/tel-04326242Test; https://theses.hal.science/tel-04326242/documentTest; https://theses.hal.science/tel-04326242/file/sygal_fusion_45427-prunotto-paul_656dc8f94103c.pdfTest |
| الإتاحة: | https://theses.hal.science/tel-04326242Test https://theses.hal.science/tel-04326242/documentTest https://theses.hal.science/tel-04326242/file/sygal_fusion_45427-prunotto-paul_656dc8f94103c.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.8E279AF4 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |