1.Expression of protease-activated receptor 1 in the basilar artery of rats following subarachnoid hemorrhage.
Gang LI ; Qingsong WANG ; Tingting LIN
Journal of Southern Medical University 2014;34(10):1523-1527
OBJECTIVETo assess the relationship between protease-activated receptor 1 (PAR1) expression in the basilar artery and cerebral vasospasm (CVS) in a rat model of subarachnoid hemorrhage (SAH).
METHODSTwenty-four SD rats were randomized into normal control group, SAH 3-days group, SAH 5-days group and SAH 7-days group. Rat models of SAH were established by two injections of blood into the cisterna magna and the behavioral changes of the rats were observed. The basilar arteries were taken at 3, 5, or 7 days following the modeling for measuring the cross-sectional area of the basilar artery and for immunohistochemical detection of PAR1 expression.
RESULTSThe SAH model rats, especially those in SAH 3-days group, presented with obvious neurological deficits, which was not found in the normal control group. CVS was not observed in the normal control group but occurred in the SAH model rats, which showed reduced cross-sectional area of the basilar artery and worsening spasm over time. The expression level of PAR1 tended to increase gradually in SAH 3-days, SAH 5-days and SAH 7-days groups. Pearson correlation analysis showed an inverse correlation between the expression of PAR1 and the cross-sectional area of the basilar artery (r=-0.779, P<0.01).
CONCLUSIONSThe expression of PAR1 increases significantly in rat basilar artery wall following SAH in positive correlation with the severity of CVS, suggesting the role of thrombin in the pathological process of CVS after SAH.
Animals ; Basilar Artery ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, PAR-1 ; metabolism ; Subarachnoid Hemorrhage ; metabolism ; Vasospasm, Intracranial ; metabolism
2.Effect of thyroxine on the expression of HIF-1α after aneurysmal subarachnoid hemorrhage in rat brain and its mechanism.
Hui RAN ; Hao YIN ; Chuang-Xi LIU ; Guo-Qiang HAN ; Fang-You GAO ; Hong-Bin SHEN ; Hang FU ; Xiao-Zhong XU ; Tao LI ; Jun MA
Chinese Journal of Applied Physiology 2020;36(6):648-652
3.Difference in Induction Rate of Experimental Cerebral Aneurysm According to High Salt, High Lipid and Normal Diet.
Hwan Young CHOI ; Jin Seok YI ; Hyung Jin LEE ; Ji Ho YANG ; Il Woo LEE
Korean Journal of Cerebrovascular Surgery 2006;8(2):102-106
OBJECTIVE: An intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Atherosclerosis is one of possible mechanism, but its contribution to aneurysm formation is unclear. Experimentally induced cerebral aneurysm rate by high lipid diet was evaluated and compared with high salt and normal diet to elucidate the role of lipid metabolism in the process of cerebral aneurysm formation. METHODS: Thirty-seven 7-week-old male Sprague-Dawley (SD) rats received a cerebral aneurysm induction procedure. The control animals (n=11) were fed a normal diet, and the experimental animals were fed a diet containing 8% salt (n=15) and high lipid (n=11) for three months. Three months after the operation, the rats were killed, their cerebral arteries were dissected, and the regions of the bifurcation of the right anterior cerebral artery-olfactory artery (ACA-OA) bifurcations were examined histologically and aneurysm induction rates among three groups were analysed. RESULTS: Average systolic blood pressures after 3 months feeding in three groups (high salt diet group, high lipid diet group and normal diet group) were 175.9+/-3.4 mmHg, 133.7+/-5.1 mmHg and 128+/-2.9 mmHg, respectively. The difference between high lipid group and normal diet group was not significant (P=0.215). The aneurysm induction rate in three group were 87%, 63% and 36%. The difference between high lipid diet group and normal diet group was significant (Pearson k2, P=0.029). CONCLUSIONS: High lipid diet significantly increase the cerebral aneurysm induction rate in experimentally induced cerebral aneurysm model of rats. That suggests a possible adverse role for hyperlipidemia leading to aneurysm formation. Further studies are necessary to elucidate the exact role of hyperlipidemia in the pathophysiology of cerebral aneurysm.
Aneurysm
;
Animals
;
Arteries
;
Atherosclerosis
;
Cerebral Arteries
;
Diet*
;
Humans
;
Hyperlipidemias
;
Intracranial Aneurysm*
;
Lipid Metabolism
;
Male
;
Rats
;
Rats, Sprague-Dawley
;
Subarachnoid Hemorrhage
4.The Effects of Nimodipine and Intracisternal Urokinase on the Content of Leukotrience C4 in the Brain Tissue after Experimental Subarachnoid Hemorrhage in Rats.
Sun Hee LEE ; Man Bin YIM ; Sang Youl KIM ; Jang Chul LEE ; Eun Ik SON ; Dong Won KIM ; In Hong KIM ; In Kyu LEE
Journal of Korean Neurosurgical Society 1994;23(4):365-374
To find out whether early lysis of subarachnoid blood clot with intracisternal urokinase as well as intraperitoneal nimodipine prevents or decrease the breakdown of arachidonic acid(AA) of the brain after subarachnoid hemorrhage(SAH), we have investigated the levels of leukotrience(LT) C4, the metabolite of the lipooxygenase pathway of the AA metabolism, in the brain tissue after experimental SAH in rats. The experimental SAH was induced by an intracisternal autologous blood injection through the catheter which was inserted into the cisterna magna. Experimental animals were assigned to one of four groups as follows. The control group(I) was that intracisternal saline irrigation was done after SAH induction. The second group(II) was treated with an injection of nimodipine(4 times per a day of 1.2 mg/Kg until sacrificed) intraperitoneally after SAH induction, the third group(III) was tried with an intracisternal urokinase irrigation(3 times per a day of 0.1 ml, 1 ml : 20,000 unit urokinase, until sacrificed) and the fourth group(IV) was treated with intraperitoneal nimodipine and intracisternal urokinase(same regimen as above). Average levels of LT C4in each group was determined at 24 hours(subgroup a), 48 hours(subgroup b), 72 hours(subgroup c) after the induction of SAH by the radioimmunoassay method. The result showed that average levels of LT C4was significantly enhanced in the brain tissue at 48 hours after SAH induction in control group(group Ia vs. IB vs. Ic : 43.85+/-15.62 vs. 184.32+/-27.46 vs. 39.29+/-12.79 pg/ml, respectively. group Ia vs. Ib vs. Ic ; p<0.01) and was decreased by intraperitoneal nimodipine, intracisternal urokinase or combination of both at 48 hours after SAH induction (group Ib vs. IIb vs. IIIb vs. IVb : 184.32+/-27.46 vs. 41.99+/-5.94 vs. 37.68+/-10.4 vs.37.38+/-9.27 pg/ml, respectively group Ib vs. IIb vs. IIIb, and IVb ; p<0.05). However, there was no significant differences among the second, the third and the fourth group(group IIa vs. IIIa vs. IVa, group IIb vs. IIIb vs. IVb and group IIc vs. IIIc vs. IVc : 41.07+/-7.06 vs. 37.97+/-4.48 vs. 31.84+/-6.07 pg/ml, 41.99+/-5.94 vs. 37.68+/-10.43 vs. 37.38+/-9.27 pg/mi and 36.41+/-6.76 vs. 37.98+/-3.45 vs. 35.59+/-8.37 pg/ml, respectively). We concluded that the early lysis of subarachnoid blood clot with intracisternal urokinase had some benefits against the damage of neurons in the early period after SAH as much as intraperitoneal injection of nimodipine. However, the benefit of the combined treatment with intraperitoneal nimodipine and intracisternal urokinase, compared to intraperioneal nimodipine or intracisternal urokinase alone, has not been cleary established.
Animals
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Brain*
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Catheters
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Cisterna Magna
;
Injections, Intraperitoneal
;
Leukotriene C4
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Metabolism
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Neurons
;
Nimodipine*
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Radioimmunoassay
;
Rats*
;
Subarachnoid Hemorrhage*
;
Urokinase-Type Plasminogen Activator*
5.Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage.
Zhi-hua YUAN ; Jian-yong ZHU ; Wei-dong HUANG ; Jiu-kun JIANG ; Yuan-qiang LU ; Miao XU ; Wei SU ; Ting-ying JIANG
Chinese Journal of Traumatology 2010;13(1):42-45
OBJECTIVETo investigate the changes and effects of arginine vasopressin (AVP) in patients with acute traumatic subarachnoid hemorrhage (tSAH).
METHODSThe plasma and cerebrospinal fluid (CSF) level of AVP, and intracranial pressure (ICP) were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale (GCS). Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group.
RESULTSCompared with control group, the levels (pg/ml) of AVP in plasma and CSF (x+/-s) in tSAH group were significantly increased within 24 hours (38.72+/-24.71 vs 4.54+/-1.38 and 34.61+/-21.43 vs 4.13+/-.26, P less than 0.01), and was remarkably higher in GCS less than or equal to 8 group than GCS larger than 8 group (50.96+/-36.81 vs 25.26+/-12.87 and 44.68+/-31.72 vs 23.53+/-10.94, P less than 0.05). The CSF AVP level was correlated with ICP (r eqaul to 0.46, P less than 0.05), but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS (r equal to -0.29, P larger than 0.05 and r equal to -0.32, P larger than 0.05, respectively). The ICP (mm Hg) in tSAH patients was elevated and higher in GCS less than or equal to 8 group than in GCS larger than 8 group (25.9+/-9.7 vs 17.6+/-5.2, P less than 0.05).
CONCLUSIONOur research suggests that AVP is correlated with the severity of tSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity of tSAH.
Adult ; Arginine Vasopressin ; blood ; cerebrospinal fluid ; Female ; Glasgow Coma Scale ; Humans ; Intracranial Pressure ; Male ; Middle Aged ; Subarachnoid Hemorrhage, Traumatic ; metabolism
6.The Cerebrospinal Fluid Levels of Leukotriene C4 in Patients with aneurysmal subarachnoid hemorrhage.
Jun Seong LEE ; Man Bin YIM ; Eun Ik SON ; Ding Won KIM ; In Hong KIM ; In Kyu LEE
Journal of Korean Neurosurgical Society 1990;19(2):197-206
We have checked levels of leukotriene(LT) C4, one of the arachidonic acid(AA) metabolites, in the lumbar, cisternal and ventricular cerebrospinal fluid(CSF) of 37 patients admitted with diagnosis of aneurysmal subarachnoid hemorrhage(SAH) and in lumbar CSF of 10 patients without aneurysmal SAH as the control group. We compared the levels of LTC4 in the CSF of the patients with aneurysmal SAH with those of the control group. We observed the changes of levels of LTC4 periodically after the onset of SAH. We devided the data of patients with aneurysmal SAH into 3 groups according to sampling days(respectively 1-4, 5-11, 12-24 days after SAH) and the clinical spasm group was compared with that of the non-spasm group. We also looked for the differences in the sampling sites and the correlation between the white blood cell counts and the levels of LTC4 in the CSF. The results of this study showed that the mean level of CSF LTC4(+/- standard deviation) of the SAH group was significantly higher than that of the control group(215.59+/-94.95 vs. 98.44+/-31.72pg/ml, respectively : P<0.001). The level of the CSF LTC4 progressively increased upto 7-8 days after SAH and decreased thereafter in the spasm group. The level of the CSF LTC4 of the spasm group was significantly higher than that of the non-spasm group(239.03+/-49.94 vs. 163.06+/-64.39pg/ml, respectively : P<0.05) in the first 4 days after SAH. There was no significant difference in the level of CSF LTC4 in the ventricular, cisternal, and lumbar CSF statistically(196.25+/-61.15 vs. 222.51+/-101.50 vs. 233.40+/-100.85pg/ml, respectively : P>0.05) even though we expected the level in the cisternal CSF to be higher than the lumbar CSF. There was no correlation between the white blood cell counts and the levels of LTC4 in the CSF(correlation coefficient=0.1240). From this study it is concluded that : 1) the AA metabolism via the lipoxygenase pathway is enhanced after SAH ; 2) the LTC4 may play a role in the pathogenesis of cerebral vasospasm, especially in the early days after SAH ; 3) the extraction of CSF via the external ventricular or cisternal drainage may decrease substances such as LTC4 which was thought to be vasoconstrictor material ; and 4) the granulocyte production of the LTC4 accounts for only a small part.
Aneurysm*
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Arachidonic Acid
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Cerebrospinal Fluid*
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Diagnosis
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Drainage
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Granulocytes
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Humans
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Leukocyte Count
;
Leukotriene C4*
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Lipoxygenase
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Metabolism
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Spasm
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Subarachnoid Hemorrhage*
;
Vasospasm, Intracranial
7.Evaluation of cerebral vasospasm resulting from subarachnoid hemorrhage with 1H-magnetic resonance spectroscopy.
Wei QUAN ; Tie-lin LI ; Guang-zhong CHEN ; Xiao-dan JIANG ; Ru-xiang XU ; Yi-quan KE ; Chuan-zhi DUAN ; Jian-ping LÜ ; Hao ZHANG ; Wei XIE ; Wen-jun ZHONG ; Ying-dong CHEN ; Fan-fan CHEN
Journal of Southern Medical University 2006;26(3):352-354
OBJECTIVETo assess the value of (1)H-magnetic resonance spectroscopy ((1)H-MRS) in evaluating cerebral vasospasm resulting from subarachnoid hemorrhage (SAH).
METHODSSix dogs were subjected to autologous non-heparinized blood injection via cisternal puncture twice at one-day interval to establish models of SAH, and another 6 received injections with normal saline in an identical manner. (1)H-MRS scan was performed on the 3rd, 7th and 14th days after the injections to measure the changes of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho). After the (1)H-MRS scan, all the dogs underwent brain digital subtraction angiography (DSA) for determining the basilar artery diameter.
RESULTSDSA results on day 3 presented development of obvious vasospasm of the basilar artery, which was most evident on day 7 and recovered obviously on day 14. (1)H-MRS results demonstrated obvious changes of NAA, Cho and Cr on days 3 and 7 in SAH model group, and NAA declined to the lowest level on day 3 followed by gradual ascending till reaching the normal level on day 14. Cho decreased slightly on day 3, then increased and reached the peak level on day 7 and then decreased. Cr rose steadily from day 3 to 14, but since day 7, the rise slowed down obviously and Cr maintain a level not significantly different from that on day 14 (P>0.05). The functional results of (1)H-MRS were consistent with the DSA results.
CONCLUSION(1)H-MRS can be used to monitor the development of cerebral vasospasm resulting from SAH as a good evaluation method for functional imaging.
Animals ; Aspartic Acid ; analogs & derivatives ; metabolism ; Choline ; metabolism ; Creatine ; metabolism ; Dogs ; Female ; Magnetic Resonance Spectroscopy ; methods ; Male ; Protons ; Subarachnoid Hemorrhage ; complications ; Time Factors ; Vasospasm, Intracranial ; diagnosis ; etiology ; metabolism
8.The relationship between hypoxia-inducible factor-1α expression and apoptosis in early brain injury after subarachnoid hemorrhage.
Qiang HU ; Cheng WU ; Jing-yin CHEN ; Feng YAN ; Jian-ru LI ; Gao CHEN
Journal of Zhejiang University. Medical sciences 2014;43(1):58-65
OBJECTIVETo investigate the association of hypoxia-inducible factor-1α (HIF-1α) expression and apoptosis in the cerebral cortex following subarachnoid hemorrhage (SAH).
METHODSSubarachnoid hemorrhage was induced by modified monofilament puncture method in rats. Thirty-five adult male Sprague-Dawley rats were randomly assigned to five groups: sham-operated group, SAH 6 h, SAH 12 h, SAH 24 h and SAH 72 h groups. HIF-1α expression was assessed by immunofluorescence staining. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique was adopted to detect apoptotic cells. Double immunolabeling was used to identify cell types with positive HIF-1α expression.
RESULTSThe expression of HIF-1α was increased at 6 h (4.65%±1.01%), peaked at 24 h (18.55%±4.23%), and decreased at 72 h (6.31%±1.15%) after SAH (P<0.05). TUNEL-positive cells were up-regulated in the brain at 6 h (7.09%±2.34%), peaked at 24 h (25.54%±7.36%), and down-regulated at 72 h (14.11%±3.03%) after SAH (P<0.05). A significant positive correlation was noted between HIF-1α positive rates and TUNEL positive rates following SAH (r=0.738, P<0.05). Double immunolabeling indicated that HIF-1α was expressed predominantly in neurons and some nuclei with positive HIF-1α were co-stained with TUNEL.
CONCLUSIONThe data indicate that HIF-1α might participate in the pathological progression of early brain injury after SAH.
Animals ; Apoptosis ; Brain ; metabolism ; pathology ; Disease Models, Animal ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; metabolism ; pathology
9.Role of glucose-regulated protein 78 in early brain injury after experimental subarachnoid hemorrhage in rats.
Qi LIU ; Dong ZHAO ; Yun-xiang JI ; Xiao-yuan HUANG ; Peng YANG ; Ye-zhong WANG ; Ting LEI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(2):168-173
Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). This study investigated the role of glucose-regulated protein 78 (GRP78) in EBI after SAH. Male Sprague-Dawley rats (n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.
Animals
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Apoptosis
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Brain Injuries
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complications
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metabolism
;
pathology
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Chromatin
;
pathology
;
Endoplasmic Reticulum Stress
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Heat-Shock Proteins
;
genetics
;
metabolism
;
Male
;
Rats
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Rats, Sprague-Dawley
;
Subarachnoid Hemorrhage
;
etiology
;
metabolism
;
pathology
10.Measurements of Malonate Concentration in Rabbit with Experimental SAH.
Jae Joong KIM ; Young Soo HA ; Seung Ryeoul PAIK ; Chung Soon CHANG ; Yu Sam KIM
Journal of Korean Neurosurgical Society 1995;24(10):1121-1129
Malonate is regarded as a reversible competitive inhibitor of succinate dehydrogenase and malate transport in the Krebs cycle and showed neurotoxicity by persistent NMDA receptor activation due to inhibition of ATP production and glutamate utilization. However, little was known about its biological effects and the range of normal concentration of malonate in central nervous system. In order to understand the relationship between malonate and vasospsasm, malonate concentrations in rabbit model of experimental subarachnoid hemorrhage were measured at 0, 4th, and 7th day following SAH in serum, cerebrospinal fluid, and urine using malonyl-CoA synthetase. The results were as follows: 1) Malonate level is increased significantly in serum at the 4th day after subarachnoid hemorrhage that followed by vasospasm(p<0.01). 2) CSF malonate concentration tends to increase at post-SAH 7th day but statistically not significant. 3) The change of urine malonate concentration is not significant. These results suggest that early increase of serum malonate level is significant because clinically important vasospam begin from the fourth through the seventh day after hemorrhage. The increased level of serum malonate at this time is due to impairment of cellular metabolism following delayed cerebral ischemia and may influence to development of vasospasm. In conclusion, the measurement of serum malonate concentration after subarachnoid hemorrhage is one of possible candidates for the early diagnosis of vasospasm.
Adenosine Triphosphate
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Brain Ischemia
;
Central Nervous System
;
Cerebrospinal Fluid
;
Citric Acid Cycle
;
Early Diagnosis
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Glutamic Acid
;
Hemorrhage
;
Ligases
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Metabolism
;
N-Methylaspartate
;
Subarachnoid Hemorrhage
;
Succinate Dehydrogenase