Serebral İskemide Moleküler ve Hücresel Mekanizmalar
Özet
Serebral iskemi, beyin dokusuna giden kan akımının azalması veya kesilmesi sonucu gelişen ve yüksek mortalite ile kalıcı nörolojik sekellere yol açabilen karmaşık bir patofizyolojik süreçtir. İskemik inme, tüm inme vakalarının büyük çoğunluğunu oluşturmakta ve küresel ölçekte önemli bir sağlık yükü yaratmaktadır. Serebral iskemi/reperfüzyon (I/R) hasarı; enerji metabolizmasının çöküşü, eksitotoksisite, iyon dengesinin bozulması, oksidatif ve nitrozatif stres, nöroenflamasyon ve kan-beyin bariyeri disfonksiyonu gibi birbiriyle ilişkili mekanizmaları içeren çok basamaklı bir kaskad ile karakterizedir. Reperfüzyonun sağlanması, iskemik dokunun kurtarılması açısından kritik olmakla birlikte, aşırı reaktif oksijen türleri üretimi ve inflamatuvar yanıtın artışı nedeniyle ikincil hasarı da tetikleyebilmektedir. Bu süreçte nekrozun yanı sıra apoptoz, nekroptoz, ferroptoz, piroptoz, otofaji ve parthanatos gibi düzenlenmiş hücre ölüm yolları aktive olur. Ayrıca iskemiyi takiben gelişen anjiyogenez, nörogenez ve sinaptogenez gibi onarım ve plastisite mekanizmaları, fonksiyonel iyileşmenin temelini oluşturur. Bu bölümde, serebral iskemi ve reperfüzyon hasarının hücresel ve moleküler patofizyolojisi, zamansal ve mekânsal dinamikleriyle birlikte kapsamlı olarak ele alınmıştır.
Cerebral ischemia is a complex pathophysiological condition resulting from a reduction or cessation of cerebral blood flow, leading to high mortality and long-term neurological disability. Ischemic stroke accounts for the majority of stroke cases and represents a major global health burden. The pathophysiology of cerebral ischemia/reperfusion (I/R) injury involves a multifactorial cascade that includes energy failure, excitotoxicity, ionic imbalance, oxidative and nitrosative stress, neuroinflammation, and blood–brain barrier dysfunction. Although reperfusion is essential for salvaging ischemic tissue, it can paradoxically exacerbate brain injury by triggering excessive reactive oxygen species production and inflammatory responses. In addition to necrosis, various forms of regulated cell death—such as apoptosis, necroptosis, ferroptosis, pyroptosis, autophagy, and parthanatos—contribute to neuronal loss following ischemic insult. Conversely, post-ischemic recovery processes, including angiogenesis, neurogenesis, and synaptogenesis, play crucial roles in neural repair and functional recovery. This chapter provides a comprehensive overview of the cellular and molecular mechanisms underlying cerebral ischemia and reperfusion injury, emphasizing their temporal and spatial dynamics.
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