Thesis (Ph.D)-Cairo University, 2024.

Bibliography: pages 109-131.

Neuroinflammation plays a pivotal role in amyloid β (Aβ) plaques formation which is among the hallmarks of Alzheimer’s disease (AD). The present study investigated the potential therapeutic benefits of baricitinib (BAR), a selective Janus kinase 2 (JAK2)/ Activator of transcription 3 (STAT3) inhibitor, in ovariectomized/ D-galactose (OVX/D-gal) treated rats as a model for AD. To induce AD, adult female rats (130-180 g) underwent bilateral ovariectomy (OVX) and were injected daily with 150 mg/kg, i.p. D-gal for 8 consecutive weeks. BAR (10 and 50 mg/kg/day) was then given orally for 14 days. BAR in a dose-dependent effect mitigated OVX/D-gal-induced aberrant activation of JAK2/STAT3 signaling pathway resulting in significant decreases in the expression of p-JAK 2, and p-STAT3 levels, along with deactivating AKT/PI3K/mTOR signaling as evidenced by deceased protein expression of p-AKT, p-PI3K, and p-mTOR. As a result, neuroinflammation was diminished as evidenced by decreased NFκβ, TNF-α, and IL-6 levels. Moreover, oxidative stress biomarkers levels as iNOS, and MDA were reduced, whereas GSH was increased by BAR. BAR administration also succeeded in reverting histopathological alterations caused by OVX/D-gal, increased the number of intact neurons (detected by Nissl stain), and diminished astrocyte hyperactivity assessed as GFAP immunoreactivity. These changes culminated in enhancing spatial learning and memory in Morris’s water maze (MWM), and novel object recognition (NOR) test. BAR could be an effective therapy against neuroinflammation, astrogliosis and cognitive impairment induced by OVX/ D-gal where inhibiting JAK2/STAT3- AKT/PI3K/mTOR seems to play a crucial role in its beneficial effect.

يعتبر مرض الاّلزهايمر من امراض التلف العصبي المزمن و يتسم بوجود لويحات مجهرية مرضية وتشابك في أنسجة المخ. يتسم مرض الاّلزهايمر بحدوث تدهور في إدراك المريض، وعادة تبدأ شكوي المريض بضعف في الذاكرة ، وفي نهاية المطاف يؤثر في مجالات متعددة معرفية وعصبية وسلوكية. قد يبدأ ظهور المرض قبل ستين عاماً في حالات الاّلزهايمر المتوارث علي خلاف الأكثر شيوعاً بعد الستين عاماً في الحالات المتفرقة الغير المتوارثة .
حتي الاّن لم يتم التوصل لدواء يساعد في شفاء المرض أو منع تدهوره حيث ان الأدوية المتوفرة حالياً تقوم بتخفيف الأعراض بشكل مؤقت. و قد تمكن الباحثون من محاكاة مرض الاّلزهايمر و ذلك عن طريق ازالة المبيضين في إناث الجرذان و حقن ال د-جالاكتوز لمدة ثماني اسابيع مما يؤدي الي حدوث اجهاد تأكسدى و تلف الخلايا العصبية فى المخ و تقليل استجابة الخلايا العصبية.

Issues also as CD.

Text in English and abstract in Arabic & English.