Subaraknoid Kanamaya Bağlı Parkinson Hastalığının Karanlık Bir Nedeni Olarak Subtalamik Çekirdek Dejenerasyonu: Deneysel Bir Ön Çalışma

Arka plan: Subtalamik çekirdek dejenerasyonu Parkinson hastalığı ile suçlanmış olsa da, subaraknoid kanamaların neden olduğu subtalamik çekirdek dejenerasyonunun belirsiz rolleri yeterince çalışılmamıştır. Bu çalışmanın amacı, subaraknoid kanama sonrası subtalamik çekirdekte meydana gelen histopatolojik değişiklikleri incelemektir. Gereç ve Yöntemler: Bu çalışmaya 21 adet yabani erkek sağlıklı tavşan dahil edildi. Denekler şu şekilde ayrıldı: kontrol (GI, n=5); SHAM 1.2 cc salin enjekte edildi (GII, n=6) ve sisterna magnaya 1.2 cc otolog kan enjeksiyonu (GIII, n=10). Üç hafta takip edildiler ve genel anestezi altında sakrifiye edildiler. Vazospazm indeksi (VSI) daire yüzey tahmin yöntemi ile, subtalamik çekirdeğin dejenere nöron yoğunlukları Stereolojik yöntemlerle tahmin edildi ve Mann Witney U testi ile analiz edildi. Bulgular: Çalışma grubunda ölen iki tavşan meningeal iritasyon bulguları ve bilinç kaybı ile temsil edildi. GIII hayvanlarında uzamış QT aralıkları, ST çöküntüleri ve düşük voltajlı QRS'ler fark edildi. Kalp-solunum hızlarının (n/dk), VSI değerlerinin ve subtalamik çekirdeğin dejenere nöron yoğunluklarının (n/mm3) sayısal belgeleri aşağıdaki gibidir: GI'de 1,05±0,03/ 219±324/21±4/8±3; GII'de 1,75±0,23/209±14/15±4/16±4; ve 2,03±0,14/175±19/19±5/123±21 GIII. Subtalamik çekirdeğin VSI değerleri ile dejenere nöron yoğunlukları arasındaki P değerleri hemen hemen eşitti: GI/GII'de p<0.005; GII/GIII'de p<0,0005 ve GI/GIII'de p<0,00001. Tartışmaç: Subaraknoid kanama, subtalamik çekirdeği besleyen arterlerin spazmına neden olarak iskemik yaralanmaya, hidrosefali ise mekanik stres yaralanmasına neden olur.

Anahtar Kelimeler:

Subarachnoid hemorrhage, Subthalamic nucleus, Parkinson’s disease, Neuronal degeneration

Subthalamic Nucleus Degeneration As A Dark Cause of Parkinson’s Disease Due to Subarachnoid Hemorrhage: A Preliminary Experimental Study

Background: Although the subtahalamic nucleus degeneration has been accused of Parkinson’s disease, the obscure roles of subtalamic nucleus degeneration induced by subarachnoid hemorrhages has not been adequately studied. The aim of the study is to examine the histopathological changes in the subthalamic nucleus after subarachnoid hemorrhage. Materials and Methods: Twenty-one wild male healthy rabbits were included in this study. The test subjects were divided as: control (GI, n=5); SHAM 1.2 cc of saline injected (GII, n=6) and 1.2 cc of autologous blood injection into cisterna magna (GIII, n=10). They followed up for three weeks and sacrificed under general anesthesia. Vasospasm index (VSI) was estimated by the circle surface estimation method, degenerated neuron densities of the subthalamic nucleus were estimated by Stereological methods and analyzed by Mann Witney U test. Results: Two rabbits dead in the study group were represented by meningeal irritation signs and unconsciousness. Prolonged QT intervals, ST depressions, and low voltage QRSs were noticed in GIII animals. Numerical documents of heart-respiratory rates (n/min), VSI values, and degenerated neuron densities of the subthalamic nucleus (n/mm3) as follows: 1.05±0.03/ 219±324/21±4/8±3 in GI; 1.75±0.23/209±14/15±4/16±4 in GII; and 2.03±0.14/175±19/19±5/123±21 GIII. P values between the VSI values and degenerated neuron densities of the subthalamic nucleus were nearly eqund: p<0.005 in GI/GII; p<0.0005 in GII/GIII and p<0.00001 in GI/GIII. Conclusion: Subarachnoid hemorrhage causes spasm of the arteries supplying the subthalamic nucleus, leading to ischemic injury, and hydrocephalus leading to mechanical stress injury.

Keywords:

Subarachnoid hemorrhage, Subthalamic nucleus, Parkinson’s disease, Neuronal degeneration,

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1. Xu C, He Z, Li J. Melatonin as a Potential Neuroprotectant: Mechanisms in Subarachnoid Hemorrhage-Induced Early Brain Injury. Front Aging Neurosci 2022; 14:899678.
2. Bartanusz V, Daniel RT, Villemure JG. Conjugate eye deviation due to traumatic striatal-subthalamic lesion. J Clin Neurosci 2005; 12(1):92-94.
3. Adeva MT, Gómez-Sánchez JC, Marcos MM, Ciudad J, Fermoso J. [Triple association of mesencephalic syndromes]. Rev Neurol 1999; 28(4):403-404.
4. Tarakad A, Jankovic J. Anosmia and Ageusia in Parkinson's Disease. Int Rev Neurobiol 2017; 133:541-556.
5. Aydin MD, Kanat A, Hacimuftuoglu A, Ozmen S, Ahiskalioglu A, Kocak MN. A new experimental evidence that olfactory bulb lesion may be a causative factor for substantia nigra degeneration; preliminary study. Int J Neurosci 2021; 131(3):220-227.
6. Dickson DW. Parkinson's disease and parkinsonism: neuropathology. Cold Spring Harb Perspect Med 2012;2(8):a009258.
7. Hasannejad-Asl B, Pooresmaeil F, Choupani E, Dabiri M, Behmardi A, Fadaie M, et al. Nanoparticles as Powerful Tools for Crossing the Blood-brain Barrier. CNS Neurol Disord Drug Targets 2023; 22(1):18-26.
8. Wattendorf E, Welge-Lüssen A, Fiedler K, Bilecen D, Wolfensberger M, Fuhr P, et al. Olfactory impairment predicts brain atrophy in Parkinson's disease. J Neurosci 2009; 29(49):15410-15413.
9. Carpenter MB, Jayaraman A. Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents. J Hirnforsch 1990; 31(5):653-668.
10. Haber SN, Groenewegen HJ, Grove EA, Nauta WJ. Efferent connections of the ventral pallidum: evidence of a dual striato pallidofugal pathway. J Comp Neurol 1985; 235(3):322-335.
11. Chiba T, Murata Y. Afferent and efferent connections of the medial preoptic area in the rat: a WGA-HRP study. Brain Res Bull 1985; 14(3):261-272.
12. Natera-Villalba E, Matarazzo M, Martinez-Fernandez R. Update in the clinical application of focused ultrasound. Curr Opin Neurol 2022; 35(4):525-535.
13. Ni JW, Takahashi M, Yatsugi S, Shimizu-Sasamata M, Yamaguchi T. Effects of YM872 on atrophy of substantia nigra reticulata after focal ischemia in rats. Neuroreport 1998; 9(16):3719-3724.
14. Cuoco JA, Guilliams EL, Rogers CM, Patel BM, Marvin EA. Recurrent Cerebral Vasospasm and Delayed Cerebral Ischemia Weeks Subsequent to Elective Clipping of an Unruptured Middle Cerebral Artery Aneurysm. World Neurosurg 2020; 141:52-58.
15. Pedard M, El Amki M, Lefevre-Scelles A, Compère V, Castel H. Double Direct Injection of Blood into the Cisterna Magna as a Model of Subarachnoid Hemorrhage. J Vis Exp 2020;(162). doi: 10.3791/61322.
16. Fricke IB, Schelhaas S, Zinnhardt B, Viel T, Hermann S, Couillard-Després S, et al. In vivo bioluminescence imaging of neurogenesis - the role of the blood brain barrier in an experimental model of Parkinson's disease. Eur J Neurosci 2017; 45(7):975-986.
17. Carvey PM, Zhao CH, Hendey B, Lum H, Trachtenberg J, Desai BS, et al. 6-Hydroxydopamine-induced alterations in blood-brain barrier permeability. Eur J Neurosci 2005; 22(5):1158-1168.
18. Aydin MD, Aydin A, Aydin A, Ahiskalioglu EO, Ahiskalioglu A, Ozmen S, et al. New Histophatological Finding About Data Destroying Amyloid Black Holes in Hippocampus Following Olfactory Bulb Lesion Like as the Universe. Archives of Neuroscience 2022;9(4):e123169
19. Eskreis-Winkler S, Zhang Y, Zhang J, Liu Z, Dimov A, Gupta A, et al. The clinical utility of QSM: disease diagnosis, medical management, and surgical planning. NMR Biomed 2017;30(4). doi: 10.1002/nbm.3668.
20. Huang E, Ong WY, Connor JR. Distribution of divalent metal transporter-1 in the monkey basal ganglia. Neuroscience 2004; 128(3):487-496.
21. Foffani G, Trigo-Damas I, Pineda-Pardo JA, Blesa J, Rodríguez-Rojas R, Martínez-Fernández R, et al. Focused ultrasound in Parkinson's disease: A twofold path toward disease modification. Mov Disord 2019; 34(9):1262-1273.
22. Schoen NB, Jermakowicz WJ, Luca CC, Jagid JR. Acute symptomatic peri-lead edema 33 hours after deep brain stimulation surgery: a case report. J Med Case Rep 2017; 11(1):103.
23. Ahlskog JE. Parkinson's disease: medical and surgical treatment. Neurol Clin 2001; 19(3):579-605
24. Astradsson A, Jenkins BG, Choi JK, Hallett PJ, Levesque MA, McDowell JS, et al. The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates--evidence from in vivo neuroimaging studies. Neurobiol Dis 2009; 35(3):348-351.
25. Porrino LJ, Lucignani G. Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate. Relevance to its action in hyperactive children. Biol Psychiatry 1987; 22(2):126-138.
26. Govsa F, Kayalioglu G. Relationship between nicotinamide adenine dinucleotide phosphate-diaphorase-reactive neurons and blood vessels in basal ganglia. Neuroscience 1999; 93(4):1335-1337.