Cerebral Vasospasm In Rabbits Research Articles

Validity of D-penicillamine in experimental cerebral vasospasm therapy

Validity of D-penicillamine in experimental cerebral vasospasm therapy

Telmisartan ameliorates oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm

Objectives: Growing evidence suggests that oxidative stress is one of the factors contributing to subarachnoid haemorrhage (SAH)-induced cerebral vasospasm. SAH-induced cerebral vasospam alters thioredoxin (Trx) cycle enzymes and thioredoxin-interacting protein (TXNIP) as an important endogenous antioxidant system. In this study, we have explored the effects of telmisartan on the vascular morphological changes, endothelial apoptosis, tissue oxidative stress status and the level of Trx cycle enzymes/ TXNIP in a rabbit SAH model.Methods: Forty male New Zealand rabbits were randomly divided into five groups of eight rabbits each: control group, sham group, SAH group, SAH + vehicle group and SAH + telmisartan group. SAH was created by a single cisterna magna blood injection. SAH + telmisartan group received telmisartan treatment (5 mg/kg intraperitoneal, once daily) for 72 h. The brainstem tissue Trx1, Trx2, Trx reductase (TrxR), TrxR1and TXNIP levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) levels and tumour necrosis factor alpha (TNF alpha) levels were investigated. Basilar artery segments were investigated for cross-sectional area, wall thickness measurements and endothelial apoptosis.Results: Telmisartan treatment restored the lowered level of Trx1, TrxR, TAS and the expression of TrxR1 seen in SAH. Telmisartan treatment also decreased TXNIP expression, TOS, MDA and TNF alpha levels. Morphological changes of cerebral vasospasm were attenuated after treatment. Endothelial apoptosis significantly reduced.Discussion: Treatment with telmisartan ameliorates oxidative stress and SAH-induced cerebral vasospasm in rabbits. These effects of telmisartan may be associated with downregulation of TXNIP and upregulation of Trx/TrxR.

The role of intravenous immunoglobulin in the treatment of cerebral vasospasm induced by subarachnoid haemorrhage: An experimental study

Objectives: The aim of this study was to determine whether intravenous immunoglobulin (IVIG) prevents cerebral vasospasm in rabbits with induced subarachnoid haemorrhage (SAH). The effect of IVIG on apoptosis in the endothelial cells of the basilar artery was also evaluated.Methods: Eighteen New Zealand white rabbits were allocated randomly into three groups. SAH was induced by injecting autologous blood into the cisterna magna. Group 1, the control group, was subjected to sham surgery (no induction of SAH). Group 2 had SAH alone and Group 3 had SAH plus IVIG. Three days after treatment, the animals were sacrificed. The basilar artery tissues were analysed histologically and the malondialdehyde levels in the brain stem tissues were evaluated biochemically.Results: Differences in the histopathological luminal areas and full wall thicknesses in the SAH plus IVIG group and the SAH group were statically insignificant (p > 0.005). The malondialdehyde level was also found to be lower in the IVIG group than in the SAH group, although this difference was not significant (p > 0.005).Conclusion: Although the IVIG treatment was revealed to have no vasodilator effect on the SAH-induced spastic basilar artery, it was shown to have a beneficial effect on the apoptosis of endothelial cells, probably via anti-inflammatory mechanisms.

Effects of nimodipine on rabbits with symptomatic cerebral vasospasm

To investigate the effects of nimodipine on symptomatic cerebral vasospasm in rabbits. Twenty four japanese white rabbits which ligation of bilateral common carotid arteries and no neurological deficits were randomized to sham-operation, subarachnoid hemorrhage (SAH) and nimodipine which injected of nimodipine 0.1 mg/kg, continuous vein administration 5 day. The behavior scores, neurological scores were observed everyday and cerebral angiography changes were measured twice by 3D-CTA, and basilar artery was removed for pathological examination after last CTA examination. In SAH group, The basilar artery were significantly vasoconstrictive on 5 days, neurological scores were increased, and the basilar artery was found apoptosis-like changes under light microscopic and electron microscope. Nimodipine group could not dilated the basilar artery arteriospasm after SAH, but it could attenuate neurological deficit, and obviously alleviate the pathological changes of basilar artery. Nimodipine could not vasodilation of basilar artery in SCVS, but obviously could alleviate neurological changes and pathological changes of basilar artery in rabbits with symptomatic cerebral vasospasm.

Experimental study of differential expression protein on cerebral vasospasm in rabbits

Objective To establish two-dimensional electrophoresis (2-DE) profiles of basilar arteries and paired normal basilar arteries of cerebral vasospasm in rabbit to identify differential expression proteins in order to find out candidates as cerebral vasospasm-related proteins. Methods 2-DE was applied to separate the total proteins of cerebral vasospasm basilar arteries and paired normal basilar arteries.After staining and analyzing by imagemaster 5.0 software. The differential proteins were identified by MALDI-TOF/TOF. Results 2-DE profiles with high resolution and reproducibility was obtained. Forty-nine protein spots were found as differentially-expressed proteins, in which 35 protein spots were successfully identified. Among the identified proteins, there were 24 over-expressed and 11 under-expressed proteins in spasm basilar arteries as compared with normal basilar arteries. Conclusions Established 2-DE patterns of rabbit spasm basilar arteries and paired normal basilar arteries and 35 differentially expressed proteins spots are identified, and which may participate in cerebral vasospasm. Key words: Proteome; Electrophoresis, gel, two-dimensional; Mass spectrometry; Vasospasm, intracranial

Effects of tetramethylpyrazine on nitric oxide/cGMP signaling after cerebral vasospasm in rabbits

Tetramethylpyrazine (TMP), an ingredient of Chinese herbal Szechwan lovage rhizome, shows vasorelaxant effect. Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity. Here, we evaluated the effect of TMP in a model of CVS and sought to identify the underlying mechanisms of action. A rabbit SAH model was established by injection of the autoblood via cisterna magna. Cerebral blood flow and arterial diameter were measured by Transcranial Doppler (TCD) and Computed Tomography Angiography (CTA). Expression of eNOS and PDE-V in basilar artery (BA) was assessed by western blots. Levels of nitric oxide (NO) in plasma and cerebral spinal fluid, and of intra-endothelium Ca(2+) were measured. Significantly reduced diameter and accelerated blood flow velocity were detected in BAs of SAH animals (P<0.05 vs. sham group). Expression of eNOS and NO was increased, and PDE-V expression was reduced by TMP.TMP ameliorated cerebral vasospasm (P<0.05 vs. SAH group), and L-NAME (a NOS inhibitor) partly abrogated the effects of TMP. TMP induced a dose-dependent increase of intra-endothelium Ca(2+). The current results demonstrated that the vasorelaxant effect of TMP was at least in part via regulation of NO/cGMP signaling.

Subarachnoid hemorrhage‐induced cerebral vasospasm stimulates mobilization of circulating progenitor cells

Mobilization of hematopoietic progenitor cells is predictive of functional recovery in stroke. In the present study, alterations in progenitor cell counts were studied in an experimental model of subarachnoid hemorrhage (SAH)‐induced cerebral vasospasm in rabbits. Injection of autologous arterial blood into cisterna magna resulted in significant vasospasm of the basilar arteries forty eight hours following injection. Concomitantly, the number of hematopoietic progenitor cells (CD34+ cells) and CD34+/Flk‐1+ cells, believed to be enriched in endothelial progenitor cells (EPCs), were significantly increased in the peripheral blood. The levels of the chemokine stromal cell‐derived factor‐1α (SDF‐1α), known to play a key role in the recruitment and retention of CXCR4+‐progenitor cells, significantly increased in the plasma of rabbits subjected to SAH. However, levels of SDF‐1α in the cerebrospinal fluid as well as the content of SDF‐1α in the spastic basilar arteries remained unaffected forty eight hours after SAH. In summary, cerebral vasospasm was accompanied by mobilization of hematopoietic progenitor cells and EPCs. We speculate that the pathogenesis of cerebral vasospasm following SAH may be mediated, in part, by impaired recruitment and homing of CXCR4+‐ progenitor cells.

Effects of different doses of human tissue kallikrein on symptomatic cerebral vasospasm in rabbits

Objective To investigate the effects of different doses of human tissue kallikrein(HTK)on symptomatic cerebral vasospasm in rabbits.Methods Forty Japanese white rabbits in which bilateral common carotid arteries were ligated without neurological deficits were randomly divided into 5 groups(n = 8 each): group A control;group B subarachnoid bemorrhage(SAH)and group C,D,E SAH+low,medium and high doses of HTK.Cerebral vasospasm(CVS)was induced by injecting non-anticoagulated autologous arterial blood 1 ml into cisterna magna twice at 48 h interval in group B,C,D,E.In group C,D,E HTK 0.002 5,0.005 0,and0.010 0 PNAU/kg in 5 ml normal saline were injected iv once a day for 14 consecutive days respectively starting after the first cisterna magna blood injection.In group A and B normal saline was injected instead of HTK.The food intake and neurological deficits were evaluated everyday.The diameter of basilar artery was detected by3D-CTA at 1 day before(T_1,baseline)and 5,7,14 d after cisterna magna blood injection(T_(2-4)).The basilar artery was removed for pathological examination at 15 clay after cisterna injection(T_5).Results The food intake was significantly decreased and the incidence of neurological deficits was increased in group B as compared with group A.Ⅳ HTK injection significantly attenuated the decrease in food intake and increase in neurological deficit incidence induced by SAH in group C,D,E as compared with group B.Vasospasm of basilar artery was observed at T_2 and T_3 in group B but not in other 4 groups.Conclusion Ⅳ HTK(0.002 5-0.010 0 PNAU/kg once a day for 14 consecutive days)can ameliorate symptomatic cerebral vasospasm in rabbits induced by SAH in a dose-dependent manner. Key words: Tissue kallikreins; Vasospasm,intracranial; Subarachnoid hemorrhage

Effects of preventive high thoracic epidural block for different periods on cerebral vasospasm in rabbits

Objective:To investigate the effects of preventive high thoracic epidural block (PHTEB) for different periods on cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH) in rabbits.Methods: T6-7 epidural space was opened and an epidural pipe was introduced to establish PHTEB model. Ropivacaine(1 g·L-1) was injected continuously through the pipe at 1 ml/h to block T1-5 sympathetic nerves. Sixty HTEB rabbits were assigned to 6 groups (n=10 each): the normal 1 day group (N1), the normal 7 day group(N7) , SAH 1 day group (S1), SAH 7 day group (S7) , PHTEB plus SAH 1 day group (HS1), and PHTEB plus SAH 7 day group (HS7). CVS was developed by injecting non-anticoagulant autologous arterial blood (0.5 ml/kg) into the cisterna magna. Transcranial Doppler (TCD) ultrasonography was used to determine Vm of the basilar artery. The lesion and spasm of the basilar artery were observed under optical microscope. Results: Compared with group N1, Vm was significantly increased in group S1 (P0.01) and increased in group HS1 (P0.05). Compared with group N7, Vm was significantly increased in group S7 (P0.05) and similar to that in group HS7 (P0.05). Vm in group S1 was significantly increased compared with group S7 (P0.05); and that in group HS1 was significantly increased compared with group HS7 (P0.05). Pathological observation showed no obvious changes in group N1 and N7. The vessel wall was shrunk and the lumina became narrow in group S1 and S7. The pathologic changes in group HS1 and HS7 were slighter than those in group S1 and S7;and Group HS7 was slighter than group HS1. Conclusion: PHTEB can relieve CVS in SAH rabbits, and the relieving effect increases with time of PHTEB.

Cerebral Vasospasm: New Strategies in Research and Treatment

Cerebral Vasospasm: New Strategies in Research and Treatment

Effects of human urinary tissue kallikreins on vasodilation of basilar artery in rabbits with symptomatic cerebral vasospasm

To evaluate the effects of urinary kallidinogenase on subarachnoid hemorrhage (SAH) in rabbits. Rabbits symptomatic cerebral vasospasm model was built though Endo method, among the 40 rabbits, 8 died or had severe nervous system syndrome, the other 32 were randomly divided into 4 groups:group A, control group, injection of normal saline to the cisterna magna;group B, subarachnoid hemorrhage;group C, injection of human urinary tissue kallikreins;group D, treated with Nimodipine. The behavior scores, neurological scores and cerebral angiography changes were observed. Food intake obviously decreased and neurological deficit were seen in group B, while which were attenuated in group C and group D, and group A was normal. Comparing the diameter of basilar artery was (1.9 +/- 0.3) mm before SAH, the diameter of group B 4 d later was (1.5 +/- 0.3) mm, 7 d later (1.4 +/- 0.3) mm, the difference was significant (P < 0.05). Comparing with group C on the day 4th and 7th, the diameters of basilar artery were significantly different (P < 0.001). Comparing with group D on the day 4th, 7th and 14th, there was no obvious improvement. Urinary kallidinogenase and Nimodipine can obviously alleviate symptomatic cerebral vasospasm in rabbits remarkably, but the former's effect of attenuating vasospasm is better than that of Nimodipine.

Comparison between one- and two-hemorrhage models of cerebral vasospasm in rabbits

Injection of blood into the cisterna magna is one of the most frequently used methods to produce subarachnoid hemorrhage (SAH) models in animals. Although the two-hemorrhage model of vasospasm is frequently used in canine and rat models, most studies with rabbits only use the one-hemorrhage model. In the present study, we accomplished a side-by-side comparison between one- and two-hemorrhage models in rabbits. A total of 38 rabbits were randomly divided into three groups, i.e. control group (n = 5), one (n = 15)- and two (n = 18)-hemorrhage model groups. The degree of cerebral vasospasm, the time course of cerebral vasospasm, the clinical behavior, and the residual amount of subarachnoid blood clots were measured on days 3, 5 and 7 after the establishment of the models. Compared with one-hemorrhage model, the time course of vasospasm in the two-hemorrhage model was more coincident with that observed in humans, produced more severe vasospasm after SAH, and had an acceptable low mortality. In conclusion, the two-hemorrhage model in rabbits is more appropriate than the one-hemorrhage model for the research on SAH or cerebral vasospasm, and thus can be used for the investigation of the mechanisms of and therapeutic approaches for cerebral vasospasm.

Delayed Intracranial Delivery of a Nitric Oxide Donor from a Controlled-release Polymer Prevents Experimental Cerebral Vasospasm in Rabbits

Decreased local availability of nitric oxide (NO) may mediate chronic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Previous reports have shown that early treatment with NO prevents vasospasm in animals. We evaluated the efficacy of controlled-release polymers that contain the NO donor diethylenetriamine (DETA-NO) for the delayed treatment of vasospasm in a rabbit model of SAH. DETA-NO 20% (wt/wt) was incorporated into ethylene-vinyl acetate (EVAc) polymers. Animals (n = 52) were randomized to two experimental groups. In the first group (n = 32), animals received SAH and implantation of either 20% DETA-NO/EVAc polymer at a dose of 0.5 mg/kg of DETA-NO (n = 16) or empty EVAc polymer (n = 16). Polymers were implanted 24 (n = 16) or 48 hours (n = 16) after SAH. In the second group (n = 20), animals received SAH and implantation of either 20% DETA-NO/EVAc polymer at a dose of 1.3 mg/kg (n = 10) or empty EVAc (n = 10). Polymers were implanted 24 (n = 10) or 48 hours (n = 10) after SAH. An additional group (n = 16) underwent either sham operation (n = 6) or SAH only (n = 10). Animals were killed 3 days after hemorrhage, and the basilar arteries were processed for morphometric measurements. Results were analyzed using Student's t test. Treatment with 20% DETA-NO/EVAc polymers at a dose of 1.3 mg/kg significantly increased basilar artery lumen patency when administered at 24 (97 +/- 6% versus 73 +/- 10%; P = 0.0396) or 48 hours (94 +/- 6% versus 71 +/- 9%; P = 0.03) after SAH. Treatment with 20% DETA-NO/EVAc polymers at a dose of 0.5 mg/kg administered 48 hours after SAH significantly increased lumen patency (82 +/- 8% versus 68 +/- 12%; P = 0.03); a dose of 0.5 mg/kg, 24 hours after SAH, did not reach statistical significance (74 +/- 7% versus 65 +/- 9%; P = 0.16). The SAH-only group had a lumen patency of 67 +/- 12%. Delayed treatment of SAH with controlled-release DETA-NO polymers prevented experimental posthemorrhagic vasospasm in the rabbit. This inhibition was dose-dependent. This further confirms the role of NO in the pathogenesis of vasospasm.

Attenuation of cerebral vasospasm in rabbits using clonidine hydrochloride, a central adrenergic agonist

The aim of this study was to assess, firstly, if exclusion of central noradrenergic areas in the hypothalamus and brain stem with the central sympathetic blocker clonidine hydrochloride could prevent the development of chronic vasospasm following experimental subarachnoid haemorrhage in rabbits and, secondly, if, parallel with the effect on cerebral arteries, changes in dopamine beta-hydroxylase concentration in the hypothalamus and brain stem could also be detected. Experimental subarachnoid haemorrhage, in concentrations of 1 ml of autologous arterial blood/1 kg of body weight was carried out on 18 New Zealand rabbits. Histological specimens were obtained by the method of perfusion fixation after the rabbits were sacrificed on day 8 after subarachnoid haemorrhage. The spastic effect of experimentally induced subarachnoid haemorrhage was determined by assessing the intensity of corrugation of the intima of the rabbit basilar artery by the previously developed method of corrugation coefficient and computer image analysis. The concentration and localization of dopamine beta-hydroxylase in noradrenaline-containing neurons was immunohistochemically assessed (semiquantitatively as 0, 1 and 2) with anti-dopamine beta-hydroxylase, at precisely defined sites of the hypothalamus and brain stem of the same rabbit. The results revealed less corrugated and smoother intima in the basilar artery and significantly lower dopamine beta-hydroxylase concentration in the control group of rabbits with sham subarachnoid haemorrhage and without any additional interventions (mean corrugation coefficient=1.123+/-0.024, P=0.35 x 10(-3); mean dopamine beta-hydroxylase=0.350+/-0.071, P=0.22 x 10(-3)), and smoother intima in the basilar artery with significantly lower concentration of dopamine beta-hydroxylase in the clonidine group (rabbits with subarachnoid haemorrhage and central alpha(2)-blocker clonidine hydrochloride at a daily dose of 0.03 mg/kg of body weight for 8 days; mean corrugation coefficient=1.177+/-0.058, P=1.7 x 10(-3); mean dopamine beta-hydroxylase=0.583+/-0.175, P=1.1 x 10(-3)). In comparison, the haemorrhage only group (rabbits with subarachnoid haemorrhage and without medication; mean corrugation coefficient=1.370+/-0.101; mean dopamine beta-hydroxylase=1.214+/-0.313) displayed intensive corrugation of the intima of the basilar artery and a significantly more intensive accumulation of dopamine beta-hydroxylase than did the control group and the clonidine group. The results of this study demonstrated that the central alpha(2)-blocker clonidine hydrochloride effectively prevents vasospasm, and diminishes the concentration of cerebral dopamine beta-hydroxylase in the hypothalamus and brain stem after experimental subarachnoid haemorrhage in rabbits.

Delayed administration of the K+ channel activator cromakalim attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.

Delayed cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage (SAH). Recent evidence indicates that the potassium channel activator cromakalim is capable of limiting cerebral vasospasm in rabbits when administered immediately after experimental SAH (i.e. before spastic constriction has been initiated). However, the ultimate clinical value of cromakalim for treating vasospasm will depend in part on its effectiveness when administered after SAH-induced constriction has already been initiated. The present study examined the effects of cromakalim on vasospasm when treatment was initiated after SAH-induced constriction was underway. New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. Cromakalim (0.03, 0.1 or 0.3 mg/kg) or vehicle was injected intravenously at 8 hour intervals beginning 24 hours post-SAH. Animals were killed by perfusion fixation 48 hours after SAH. Basilar arteries were removed and sectioned, and cross-sectional area was measured. The average cross sectional areas of basilar arteries were reduced by 64% and 68% in the SAH-only and SAH + vehicle groups, respectively. Treatment with cromakalim dose-dependently attenuated SAH-induced constriction. The groups treated with 0.03, 0. 1, and 0.3 mg/kg cromakalim exhibited average decreases in cross-sectional area of 57%, 42%, and 19%, respectively. These findings indicate that cromakalim dose-dependently attenuates cerebral vasospasm when administered 24 hours after experimental SAH in the rabbit. The results suggest K(ATP) channel activators, such as cromakalim. could be of benefit for reversing cerebral vasospasm after aneurysmal SAH.

Effect of U88999E on Experimental Cerebral Vasospasm in Rabbits

U88999E, 7-[4-(4, 4′-difluorobenzhydryl)piperazino-1-methyl]-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one hydrochloride, is a recently developed tropolone derivative that inhibits lipid peroxidation and also acts as a calcium antagonist. The effects of U88999E on basilar artery tone were examined in two model systems: 1) an in vitro preparation of arterial rings that measures isometric tension, and 2) an in vivo model of cerebral vasospasm measuring arterial diameter. U88999E elicited dose-dependent relaxation of preconstricted arterial rings maintained in vitro. Ring preparations were preconstricted using elevated potassium (40 mmol/L), uridine triphosphate (10−3 mol/L), or endothelin-1 (10−8 mol/L); U88999E reversed these constrictions across a concentration range of 10−8 to 10−5 mol/L. The potency of U88999E for relaxing preconstricted vessels was slightly less than that observed for flunarizine or diltiazem. A dose-dependent, relaxing effect of U88999E on potassium-induced contractions was observed in the presence of calcium concentrations ranging from 0.03 to 20 mmol/L. Vasospasm of basilar arteries after subarachnoid hemorrhage was inhibited in a dose-dependent and significant manner by intravenous injections of U88999E. Animals receiving intraperitoneal injections of U88999E also exhibited a tendency for reduced vasospasm; however, this effect did not achieve statistical significance. These findings suggest that U88999E may be useful in the prevention of cerebral vasospasm after subarachnoid hemorrhage.

Effect of U88999E on Experimental Cerebral Vasospasm in Rabbits

U88999E, 7-[4,(4, 4'-difluorobenzhydryl)piperazino-1-methyl]-4- isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one hydrochloride, is a recently developed tropolone derivative that inhibits lipid peroxidation and also acts as a calcium antagonist. The effects of U88999E on basilar artery tone were examined in two model systems: 1) an in vitro preparation of arterial rings that measures isometric tension, and 2) an in vivo model of cerebral vasospasm measuring arterial diameter. U88999E elicited dose-dependent relaxation of preconstricted arterial rings maintained in vitro. Ring preparations were preconstricted using elevated potassium (40 mmol/L), uridine triphosphate (10(-3) mol/L), or endothelin-1 (10(-8) mol/L); U88999E reversed these constrictions across a concentration range of 10(-8) to 10(-5) mol/L. The potency of U88999E for relaxing preconstricted vessels was slightly less than that observed for flunarizine or diltiazem. A dose-dependent, relaxing effect of U88999E on potassium-induced contractions was observed in the presence of calcium concentrations ranging from 0.03 to 20 mmol/L. Vasospasm of basilar arteries after subarachnoid hemorrhage was inhibited in a dose-dependent and significant manner by intravenous injections of U88999E. Animals receiving intraperitoneal injections of U88999E also exhibited a tendency for reduced vasospasm; however, this effect did not achieve statistical significance. These findings suggest that U88999E may be useful in the prevention of cerebral vasospasm after subarachnoid hemorrhage.

Effect of intracisternal and intravenous calcitonin gene-related peptide on experimental cerebral vasospasm in rabbits.

We investigated the vasodilatory effect of intracisternal (i.c.) and intravenous (i.v.) administration of calcitonin gene-related peptide (CGRP) on arterial narrowing after experimental subarachnoid hemorrhage (SAH). Forty-one rabbits were divided into five groups: control (normal animals); SAH plus i.c. infusion of vehicle; SAH plus i.c. infusion of CGRP; SAH plus i.v. infusion of vehicle; SAH plus i.v. infusion of CGRP. In all but the control group, either CGRP (100 ng/kg/min) or vehicle solution was infused for two hours immediately prior to sacrifice by perfusion-fixation. A morphometric technique was employed to measure the luminal diameter of rabbit basilar arteries two days after SAH. The diameter of the basilar arteries in either the i.c. or i.v. CGRP groups was significantly greater than that of the respective vehicle group (i.c., p < 0.001; i.v., p < 0.01). Although there was no significant difference in systemic arterial blood pressure after infusion between the i.c. vehicle and i.c. CGRP groups, i.v. CGRP caused significant hypotension. Our results suggest that exogenous CGRP has some therapeutic potential for arterial narrowing after SAH not only by intrathecal application, but also by systemic use.

Preventive Effect of Synthetic Serine Protease Inhibitor, FUT-175, on Cerebral Vasospasm in Rabbits

Preventive Effect of Synthetic Serine Protease Inhibitor, FUT-175, on Cerebral Vasospasm in Rabbits