The influence of noradrenergic blockade on vasospasm and the quantity of cerebral dopamine beta-hydroxylase following subarachnoid haemorrhage in rabbits.
BACKGROUND
The aim of this study of experimental subarachnoid haemorrhage (SAH) and exclusion of the sympathetic nervous system (SNS) in rabbits was to find out if changes in the central noradrenergic areas of the hypothalamus and brain stem could be ascertained, in parallel with measurement of the intensity of chronic cerebral vasospasm in the basilar arteries.


METHODS
Histologic specimens were prepared by perfusion fixation on day 8 after the SAH. The spastic effect of experimentally induced SAH in New Zealand rabbits was investigated: firstly, using our previously developed method for measuring the corrugation coefficient (CC) of the vessel intima on precisely defined locations of the basilar artery (BA) with the aid of computer image analysis; and secondly, by immunohistochemical assessment of the concentration and localization of dopamine beta-hydroxylase (DBH), using anti-DBH, at precisely defined sites of the hypothalamus and brain stem of the same rabbit.


RESULTS
The intima of the BA, assessed by CC, was significantly less corrugated and had significantly less DBH in group A (the control group without SAH and without additional interventions; mean CC = 1.192, P = 0.004; median DBH = 0.50, P = 0.044), in group C (SAH and alpha-blocker phenoxybenzamine; mean CC = 1.142, P = 0.000; median DBH = 0.75, P = 0.001), and in group D (SAH and cervical gangliectomy; mean CC = 1.210, P = 0.003; median DBH = 0.50, P = 0.002) compared with group B (rabbits with SAH and without medication). Group B showed a significantly more intensive accumulation of DBH (median DBH = 1.15) and, according to the CC (mean CC = 1.369), more intensive corrugation of the intima of BA than all other groups. The correlation between CC and DBH for all the rabbits (groups A, B, C and D together) was significantly positive (Spearman Rho = 0.470; p = 0.010).


CONCLUSIONS
The results of this study demonstrated: firstly, an intensive excitatory influence of SAH on the quantity of DBH in central noradrenergic areas in the hypothalamus and brain stem; secondly, a very effective influence of peripheral and systemic sympathetic exclusion on lowering the quantity of central sympathetic DBH; thirdly, that the changes in the BA of individual rabbits occur simultaneously with corresponding changes in DBH-containing neurons, thus suggesting the likelihood of SNS involvement in the pathogenesis of post-SAH vasospasm in rabbits.
Bunc
Gorazd
G
Department of Neurosurgery, Maribor Teaching Hospital, Maribor, Slovenia. gorazd.bunc@sb-mb.si
Kovacic
Srecko
S
Strnad
Simona
S
D000818:Animals; D001488:Basilar Artery / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D001933:Brain Stem / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006652:Histological Techniques; D007031:Hypothalamus / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D007150:Immunohistochemistry; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000502:physiology / Q000503:physiopathology*; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D004299:Dopamine beta-Hydroxylase