Deneysel Migren Modelleri
Özet
Migren, tekrarlayan baş ağrısı atakları, nörolojik ve sistemik semptomlarla seyreden, yaşam kalitesini olumsuz etkileyen karmaşık bir nörovasküler beyin hastalığıdır. Hastalığın tam olarak anlaşılamayan patofizyolojisi uyarıcı faz, aura evresi ve baş ağrısı fazı olmak üzere üç klinik aşamadan oluşur. Bu süreçte kraniyal damarlarda vazodilatasyon, nörojenik inflamasyon ve nosiseptif nöronların duyarlılaşmasında kalsitonin geni ile ilişkili peptidin (CGRP) önemli rolleri bulunmaktadır. Migrenin nörobiyolojik mekanizmalarını çözmek ve yeni terapötik ajanlar geliştirmek amacıyla çeşitli deneysel hayvan modelleri uygulanmaktadır. Bu modeller arasında prostaglandin, histamin ve serotonin içeren inflamatuar karışımların dural uygulanması, nitrik oksit donörü olan nitrogliserin (NTG) infüzyonu ve ilaç aşırı kullanımı baş ağrısı (MOH) modelleri yer almaktadır. Ayrıca, ailesel hemiplejik migren (FHM) mutasyonlarını temel alan transgenik ve knock-in genetik fare modelleri ile migren aurasının altında yatan mekanizma olarak kabul edilen kortikal yayılan depresyon (KYD) modelleri sıklıkla tercih edilmektedir. KYD modellerinde, mekanik, elektriksel veya potasyum klorür (KCl) gibi kimyasal uyaranlarla hücresel ve iyonik dengesizlikler tetiklenerek trigeminal nosiseptif sistemin aktivasyonu incelenmektedir. Mevcut deneysel modellerin insandaki migren fenotipini tam olarak karşılayamamasına ve bazı dezavantajlar barındırmasına rağmen, bu çalışmalar migren patofizyolojisinin anlaşılmasında ve etkili tedavi yöntemlerinin keşfedilmesinde hayati bir öneme sahiptir.
Migraine is a complex neurovascular brain disease characterized by recurrent headache attacks, neurological, and systemic symptoms, which negatively affects the quality of life. The pathophysiology of the disease, which is not yet fully understood, consists of three clinical phases: the premonitory phase, the aura phase, and the headache phase. In this process, calcitonin gene-related peptide (CGRP) plays crucial roles in cranial vasodilation, neurogenic inflammation, and the sensitization of nociceptive neurons. Various experimental animal models are implemented to unravel the neurobiological mechanisms of migraine and to develop new therapeutic agents. These models include the dural application of inflammatory soups containing prostaglandins, histamine, and serotonin; the infusion of nitroglycerin (NTG), a nitric oxide donor; and medication overuse headache (MOH) models. Additionally, transgenic and knock-in genetic mouse models based on familial hemiplegic migraine (FHM) mutations, along with cortical spreading depression (CSD) models, which are considered the underlying mechanism of migraine aura, are frequently preferred. In CSD models, cellular and ionic imbalances are triggered by mechanical, electrical, or chemical stimuli such as potassium chloride (KCl) to investigate the activation of the trigeminal nociceptive system. Although current experimental models cannot fully replicate the human migraine phenotype and possess certain limitations, these studies are of vital importance for understanding migraine pathophysiology and discovering effective treatment modalities.
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