Role of carotid body for neuronal protection in experimental subarachnoid haemorrhage

Öz

Objective: Carotid bodies are known as main arterial chemoregulatory units. Despite well known that carotid bodies have an important role in cerebral circulation and blood pH regulation, their roles has not been investigated in subarachnoid haemorrhage. We investigated whether there is neuroprotective effect of neuron density of carotid bodies on the brain in subarachnoid haemorrhage. Methods: Twenty hybrid rabbits were studied. Four of them were used as reference group (n=4) and the remaining was obliged to subarachnoid haemorrhage by injecting autologous blood into their cisterna magna (n=16) and sacrificed after one month. All carotid bodies and brains examined histopathologically using by stereologic methods. The relationship between the neuronal density of carotid body and degenerated neuron density of the hippocampus were compared statistically. Results: Five rabbits with subarachnoid haemorrhage dead during the follow-up time (n=5). The average neuronal density of carotid body was 4500±500 cells/mm3 and of hippocampus 170.000±17.000 cell/mm3 in normal rabbit family. The degenerated neuron density of the hippocampus was 20.000±3.000 cells/mm3 in rabbits with have high neuron density of carotid body and was 65.000±8.000 cells/mm3 in rabbits with low neuron density of carotid body. The differences between the neuronal density of carotid body and the degenerated neuron numbers of the hippocampus were significant. Conclusion: The neuron density of carotid body may play an important role on the protection of brain in subarachnoid haemorrhage.

Anahtar Kelimeler

• Subarachnoid haemorrhage, carotid body, hippocampus, neurodegeneration, cerebral ischemia

Deneysel subaraknoid kanamada karotid cismin nöron korumasındaki rolü

Öz

Amaç: Karotid cisimler, temel arteriyel kemoregulatuar üniteler olarak bilinirler. Karotid cisimlerin serebral sirkülasyonda ve kan pH regülasyonunda önemli bir rolü olduğu iyi bilinmesine rağmen, subaraknoid kanamadaki rolleri henüz araştırılmamıştır. Biz subaraknoid kanamada karotis cisim nöron yoğunluğunun beyin üzerinde nöron koruyucu etkisinin olup olmadığını araştırdık. Yöntemler: Yirmi hibrit tavşan çalışmada kullanıldı. Bunların dört tanesi (n=4) referans grup olarak kullanıldı ve kalanların (n=16) sisterna magna\'ları içerisine otolog kan enjeksiyonu yapılarak subaraknoid kanama geliştirildi ve bir ay sonra hayvanların yaşam süresi sonlandırıldı. Tüm karotid cisim ve beyin dokuları, stereolojik metodlar kullanılarak histopatolojik olarak incelendi. Karotid cisimdeki nöronal yoğunluk ile hipokampustaki dejenere nöron yoğunluğu arasındaki ilişki istatistiksel olarak karşılaştırıldı. Bulgular: Subaraknoid kanaması olan beş tavşan takip süresi içerisinde öldü (n=5). Normal tavşan ailesinde karotid cisim ortalama nöronal hücre yoğunluğu 4500±500/mm3 ve hipokampus ortalama nöronal hücre yoğunluğu 170,000±17,000/mm3 olarak saptandı. Karotid cisminde yüksek nöron yoğunluğu olan tavşanların hipokampuslarındaki dejenere nöron hücre yoğunluğu 20,000±3,000/mm3 iken karotid cisminde düşük nöron yoğunluğu olan tavşanların hipokampuslarındaki dejenere nöron hücre yoğunluğu 65,000±8,000/mm3 saptandı. Karotid cismin nöronal yoğunluğu ve hipokampusun dejenere nöron sayıları arasındaki farklılık istatistiksel olarak anlamlıydı. Sonuç: Karotid cismin nöron yoğunluğu, subaraknoid hemorajide beyin dokusunun korunmasında önemli bir rol oynayabilir.

Anahtar Kelimeler

• Subaraknoid hemoraji, karotid cisim, hipokampüs, nörodejenerasyon, serebral iskemi

Kaynakça

1. Doux JD, Yun AJ. The link between carotid artery disease and ischemic stroke may be partially attributable to au- tonomic dysfunction and failure of cerebrovascular auto- regulation triggered by Darwinian maladaptation of the ca- rotid baroreceptors and chemoreceptors. Med Hypotheses 2006;66:176-81.
2. Kusakabe T, Matsuda H, Hayashida Y. Hypoxic adaptation of the rat carotid body. Histol Histopathol 2005;20:987-97.
3. Rey S, Iturriaga R. Endothelins and nitric oxide: vasoactive modulators of carotid body chemoreception. Curr Neuro- vasc Res 2004;1:465-73.
4. Oikawa S, Hirakawa H, Kusakabe T. Autonomic cardio- vascular responses to hypercapnia in conscious rats: the roles of the chemo- and baroreceptors. Auton Neurosci 2005;117:105-14.
5. Bederson JB, Germano IM, Guarino L. Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid haemorrhage in the rat. Stroke 1995; 26:1086-91.
6. Schultz HD, Sun SY. Chemoreflex function in heart failure. Heart Fail Rev 2000;5:45-56.
7. De Toma G, Nicolanti V, Plocco M, et al. Baroreflex failure syndrome after bilateral excision of carotid body tumors: an underestimated problem. J Vasc Surg 2000; 31:806-10.
8. Adams HPJ, Kassell NF, Torner JC. Early management of subarachnoid haemorrhage: A report of the Cooperative Aneurysm Study. J Neurosurg 1981;46:454-66.

9. Naveri L, Stromberg C, Saavedra JM. Angiotensin IV re- verses the acute cerebral blood flow reduction after experi- mental subarachnoid haemorrhage in the rat. J Cereb Blood Flow Metab 1994;14:1096-99.
10. Bederson JB, Guarino L, Germano IM. Failure of chang- es in cerebral perfusion pressure to account for ischemia caused by subarachnoid haemorrhage: A new experimental model. Soc Neurosci Abstr 1994;20:224-8.
11. Broderick JP, Brott TG, Duldner JE. Initial and recurrent bleeding are the major causes of death following subarach- noid haemorrhage. Stroke 1994;25:1342-47.
12. Delgado TJ, Brismar J, Svendgaard NA. Subarachnoid haemorrhage in the rat: Angiography and fluorescence mi- croscopy of the major cerebral arteries. Stroke 1985;16:595- 602.
13. Bederson JB, Levy AL, Ding WH, et al. Acute vasocon- striction after subarachnoid haemorrhage. Neurosurgery 1998;42:352-60.
14. Cruz-Orive LM, Weibel ER. Recent stereological methods for cell biology: a brief survey. Am J Physiol 1990;258:148- 56.
15. Gundersen HJ, Bendtsen TF, Korbo L, et al. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMI 1988;96:379- 94.
16. Sterio DC. The unbiased estimation of number and siz- es of arbitrary particles using the disector. J Micros. 1984;134:127-36.
17. Ostrowski RP, Colohan RT. Mechanisms of hyperbaric ox- ygen-induced neuroprotection in a rat model of subarach- noid haemorrhage. J Cerebral Blood Flow & Metabolism 2005;25:554-71.
18. Aydin MD, Ozkan U. Protective effect of posterior cere- bral circulation on carotid body ischemia. Acta Neurochir 2002;144:369-72.
19. Yu G, Fournier C, Hess DC. Transplantation of carotid body cells in the treatment of neurological disorders. Neurosci Biobehav Rev, 2005;28:803-10.
20. Unur E, Aycan K: Arteries of the carotid body in rats. Anat Histol Embriol 1999;28:167-69.
21. Montero SA, Yarkov A, Lemus M, et al. Carotid Chemo- receptor Reflex Modulation by Arginine-Vasopressin Mi- croinjected into the Nucleus Tractus Solitarius in Rats. Ar- chives of Medical Research 2006;37:709-16.
22. Berger AJ and Mitchel RA, Severinghaus JW. Regulation of respiration (first of three parts). N Engl J Med 1977;297:92- 7.