Vasospasm Index Research Articles

The Enigma of Basilar Artery Dissections Secondary to Vasospasm Following Subarachnoid Hemorrhage. Exploration of the Unknown Effect of Superior Cervical Ganglia: A Preliminary Experimental Study.

Life-threatening basilar artery dissection (BAD) can be seen following subarachnoid hemorrhage (SAH), but it is not clear whether SAH causes dissection, or not. This study aims to investigate the relationship between degenerative changes in the superior cervical ganglia and the dissection rate of the basilar artery. In this study, after 3 weeks of experimental SAH, animals were decapitated. Eighteen rabbits were divided into three groups according to their vasospasm indices. The basilar arteries were examined by anatomical and histopathologic methods. Basilar dissection with high vasospasm index (VSI) value (VSI > 3) was detected in six animals (group I); severe basilar edema and moderate VSI value (>2.4) were detected in seven rabbits (group II); and slight VSI value (<1.5) was detected in five subjects (group III). The degenerated neuron densities of the superior cervical ganglia were 12 ± 4 n/mm3 in group I, 41 ± 8 n/mm3 in group II, and 276 ± 78 n/mm3 in group III. The dissected surface values/lumen values were calculated as (42 ± 1)/(64 ± 11) in G-I, (21 ± 6)/(89 ± 17) in group II, and (3 ± 1)/(102 ± 24) in group III. If we look at these ratios as a percentage, it was 62% in group I, 23% in group II, and 5% in group III. Inverse relationship between the degenerated neuron densities of the superior cervical ganglia and the dissected surface values of the basilar artery was observed. Common knowledge is that BAD may lead to SAH; however, this study indicates that SAH is the cause of BAD.

Changes in the Urethral Artery After Experimental Subarachnoid Hemorrhage-Induced Injury of the Pudendal Ganglion and Onuf's Nucleus Junction.

Onuf's nucleus is an anatomical structure essential in the regulation of urogenital functions. Lumbosacral pathologies may cause changes in urogenital circulation due to Onuf's nucleus injury; however, there is limited evidence corroborating the relationship between spinal cord injury and urethral artery changes. We used 23 sexually mature male rabbits-5 rabbits in the control group (GI), 5 rabbits in the sham group (GII), and 13 rabbits in the experimental group (GIII; received autologous blood transfusion into the T12-L1 subarachnoid space to induce subarachnoid hemorrhage (SAH). The GIII underwent a S1-3 laminectomy after 2 weeks and was decapitated. Histologic specimens were prepared to examine changes in Onuf's nucleus, pudendal ganglion, and urethral arteries. The density of damaged neurons and vasospasm index (VSI) in the urethral artery were evaluated. The mean density of damaged neurons (n/mm3 ) in Onuf's nucleus and pudendal ganglia (S3) and the mean VSI of the 3 groups were as follows-GI: 6 ± 2 per mm3 , 12 ± 4 per mm3 , and 1.63 ± 0.25, respectively; GII: 27 ± 6 per mm3 , 221 ± 62 per mm3 , and 1.97 ± 0.36, respectively; GIII: 154 ± 41 per mm3 , 1890 ± 541 per mm3 , and 3.04 ± 0.95 (P < .05 each for GI/GII, GI/GIII, and GII/GIII). Neuronal damage criteria, such as cytoplasmic condensation and cytoplasmic halo formation, were more prominent in GIII. SAH can lead to ischemia of the Onuf's nucleus-pudendal nerve structures due to urethral artery spasm, resulting in urogenital complications.

Predictive Role of Posterior Communicating Artery Spasm on Axonal Degeneration in Oculomotor Nerve Root Following Subarachnoid Hemorrhage: Experimental Study

Background: The oculomotor nerve root's medial aspect in the cisternal space is closely associated with the posterior communicating artery and receives blood supply from it. This study investigates whether ischemic damage to oculomotor nerve roots results from posterior communicating artery spasm in subarachnoid hemorrhages.&#x0D; Methods: A total of 18 rabbits participated in this study. Baseline pupil diameters were measured using sunlight and ocular tomography. Rabbits were divided into control (GI, n=5), SHAM (GII, n=5; 0.75 cc serum physiologic injection), and subarachnoid hemorrhage-induced groups (GIII, n=8; 0.75 cc autolog blood injection). Pupil diameters were re-measured after the experiment and daily for three weeks. The animals were observed for one week before euthanasia. The posterior communicating artery vasospasm index (VSI) was determined using the wall surface/lumen surface ratio. Stereological methods were employed to examine the normal and degenerated axon densities of the oculomotor nerves. The Kruskal-Wallis and Mann-Whitney U tests were used to evaluate degenerated axon density (n/mm2) and VSI values. A p-value of less than 0.005 was considered significant.&#x0D; Results: Degenerated axon numbers (n/mm2) and VSI values of the posterior communicating artery were as follows: 3±1/0.936±0.212 in GI; 18±4/1.578±0.235 in GII; and 212±34/2.515±0.347 in GIII. The p-values were p

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

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.&#x0D; 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.&#x0D; 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

Protective Felix Culpa Effect of Superior Sympathetic Cervical Ganglion Degenerations on Prevention of Basilar Artery Spasm After Subarachnoid Hemorrhage: A Preliminary Experimental Study

Posterior cerebral blood flow is regulated by the basilar arteries (BAs). Vasospasm of BAs can occur after subarachnoid hemorrhage (SAH). Superior cervical sympathetic ganglia (SCG) fibers have a vasoconstrictor effect on the BA. We aimed to investigate the relationship between the degenerated neuron density of the SCG and the severity of BA vasospasm after experimental SAH. Twenty-four rabbits were used. Five were used as the control group, and 5 were used as the sham group. Experimental SAHs were performed in the remaining 14 animals (study group) by injecting homologous blood into the cisterna magna. After 3 weeks of injection, neuron densities of SCG and the severity of BA vasospasm index values (VSI) were examined histopathologically and compared statistically. The mean VSI was 0.669 ± 0.1129 in the control group, 0.981 ± 0.159 in the sham group, and 1.512 ± 0.298 in the study group. The mean degenerated neuronal density of SCG was 436 ± 79/mm3 in severe vasospasm (n= 3), 841 ± 101/mm3 in moderate vasospasm (n= 4), and 1.921 ± 849/mm3 in the less vasospasm detected animals (n= 6). This study shows an inverse relationship between the degenerated neuronal density in the SCG and VSI values. This finding indicates a diminished sympathetic input from the SCG, resulting in a beneficial effect (the felix culpa) by dilating the lumen diameter of the BA, so SCG degeneration after SAH protects the BA spasm.

Predictive role of trigeminal ganglion ischemia on scalp survival affected by temporal artery diameters: The first experimental study

Scalp arteries are mainly innervated by trigeminal, facial, and vagal nerves. The ischemic neurodegeneration of the trigeminal ganglion can impede scalp circulation via vasospasm-creating effects. This study was designed to investigate whether there is any link between the vasospasm index of deep temporal arteries and ischemic neuron densities of the trigeminal ganglion after subarachnoid hemorrhage. The study subjects included five normal control rabbits, six sham rabbits, and nine rabbits chosen from a formerly established experimental subarachnoid hemorrhage group created by cisternal homologous blood injection (0.75mL). These rabbits, all male, were followed up for 3 weeks. The trigeminal ganglion and deep temporal artery vasospasm indexes were examined by stereological methods. Ischemic neuron densities of the trigeminal ganglion and vasospasm index values of deep temporal arteries were compared statistically. Postmortem examinations showed important vasospasms of deep temporal arteries, foramen magnum herniations, and neurodegeneration of the trigeminal ganglion. The mean vasospasm index values and degenerated neuron densities of the trigeminal ganglion were determined as 1.03±0.13 and 10±3/mm3 (p > 0.5) in the control group, 1.21±0.18 and 35±9/mm3 in the sham group (p < 0.005 for sham vs. control), and 2.54±0.84 and 698±134/mm3 in the experimental group (p < 0.0005 for sham vs. control and p < 0.00001 for study vs. control). There was an inverse relationship between the vasospasm index values and the degenerated neuronal density of the trigeminal ganglion. The high degenerated neuron density in the trigeminal ganglion had a facilitative effect on temporal artery vasospasm. Trigeminal ganglion neurodegeneration may promote temporal artery vasospasms after subarachnoid hemorrhage, which has not been previously mentioned in the literature.

Assessment relationship between the femoral artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: an experimental study.

Animal proof of principle study. To investigate neurodegeneration in rabbit L4-dorsal root ganglion (DRG) cells by creating experimental spinal subarachnoid hemorrhage (SAH), we aimed to show the neuronal pathway between L4-DRG and femoral artery. Ataturk University, Medical Faculty, Animal Laboratory, Erzurum, Turkey. This study was designed on 20 rabbits, which were randomly divided into three groups: Spinal SAH (n = 8), SHAM (n = 6), and control (n = 6) groups. Animals were followed for 20 days and then killed. Vasospasm index values of the femoral artery and neuron density of L4-DRG were analyzed. The number of degenerated neurons in DRG was higher in the spinal SAH than the control and SHAM groups (p < 0.001). But, the difference between the control group and the SHAM group was not significant. Normal neuron densities were significantly lower in the spine SAH group compared to the SHAM and the control groups. There was a statistically significant increase in vasospasm index values of the spinal SAH group compared to the other two groups (p < 0.001). Decreased volume of the femoral artery lumen was showed in animals with spinal SAH compared with control and SHAM groups. Increased degeneration of the L4 dorsal root ganglion in animals with spinal SAH was also demonstrated. Our findings might shed light on the planning of future experimental studies and evaluating the clinical relevance of such studies.

Cranial hyperthermia resulting from decreased parotid gland salivation induced by ischemic degeneration of glossopharyngeal network in subarachnoid hemorrhage

Objective: We speculated that subarachnoid hemorrhage (SAH) induces ischemic lesions in the cranial parasympathetic nerves, which may decrease saliva secretion and lead to hyperthermia. We tested this hypothesis by examining histologic features of parotid glands and glossopharyngeal nerves (GPNs) in a rabbit model of SAH.&#x0D; Material and Methods: Rabbits (n = 25) were divided into control (n = 5), sham (n = 5), and SAH (n = 15) groups. Animals in the sham and SAH groups were examined over a 3-week period before sacrifice. Salivation score (SC) was determined by measuring the mean wetted area of an orally inserted cotton ball. Sections of parotid glands and intracranial and intraparotideal branches of the GPNs were stained with hematoxylin and eosin and SAH-induced damage was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling of apoptotic cells. Specimens were stereologically examined to determine saliva-filled total vesicle volume (TVV) per cubic meter; vasospasm index (VSI) based on wall/lumen ratio of parotid glands arteries, and degenerated neuron density (DND) of glossopharyngeal ganglia.&#x0D; Results: The mean oral temperature was 36.9°C. In the control group, mean values were as follows: SC, 46±8 mm2; DND, 19±4/mm3; VSI, 1.065±0.049; and TVV, (780±1187) × 106/µm3. In the sham group, mean values were as follows: SC, 31±6 mm2; DND, 98±23/mm3; VSI, 1.67±0.32; and TVV, (617±110) × 106/µm3. In the low hyperthermia SAH group, mean values were as follows: SC, 16±5 mm2; DND, 1520±261/mm3; VSI, 2.12±0.21, and TVV, (314±98) × 106/µm3. In the high hypothermia SAH group, mean values were as follows: SC, 9±2 mm2; DND, 3210±912/mm3; VSI, 3.18±0.30; and TVV, (432±99) × 106/µm3.&#x0D; Conclusions: Decreased salivary secretion due to secretory gland atrophy originated from ischemia-induced GPN network degeneration at the brainstem, which may be responsible for cranial hyperthermia following SAH.

Effects of nimodipine combined with betahistine on CRP and other inflammatory cytokines and vascular endothelial function in patients with hypertensive cerebral vasospasm.

This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (p < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p < 0.05), but negatively correlated with changes in NO (p < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p < 0.05), and there were no significant differences of adverse reactions between the two groups (p > 0.05). For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body's aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.

Letter to the Editor Regarding the Manuscript of “The Longest Angiographic and Clinical Follow-Up of Microsurgically Treated Giant Intracranial Aneurysms: Experience with 70 Cases”

Posterior cerebral blood flow is regulated by the basilar arteries (BAs). Vasospasm of BAs can occur after subarachnoid hemorrhage (SAH). Superior cervical sympathetic ganglia (SCG) fibers have a vasoconstrictor effect on the BA. We aimed to investigate the relationship between the degenerated neuron density of the SCG and the severity of BA vasospasm after experimental SAH.Twenty-four rabbits were used. Five were used as the control group, and 5 were used as the sham group. Experimental SAHs were performed in the remaining 14 animals (study group) by injecting homologous blood into the cisterna magna. After 3 weeks of injection, neuron densities of SCG and the severity of BA vasospasm index values (VSI) were examined histopathologically and compared statistically.The mean VSI was 0.669 ± 0.1129 in the control group, 0.981 ± 0.159 in the sham group, and 1.512 ± 0.298 in the study group. The mean degenerated neuronal density of SCG was 436 ± 79/mm3 in severe vasospasm (n = 3), 841 ± 101/mm3 in moderate vasospasm (n = 4), and 1.921 ± 849/mm3 in the less vasospasm detected animals (n = 6).This study shows an inverse relationship between the degenerated neuronal density in the SCG and VSI values. This finding indicates a diminished sympathetic input from the SCG, resulting in a beneficial effect (the felix culpa) by dilating the lumen diameter of the BA, so SCG degeneration after SAH protects the BA spasm.

New Histopathologic Evidence for the Parasympathetic Innervation of the Kidney and the Mechanism of Hypertension Following Subarachnoid Hemorrhage.

The Cushing response was first described in 1901. One of its components is elevated systemic blood pressure secondary to raised intracranial pressure. However, controversy still exists in its pathophysiologic mechanism. Hypertension is attributed to sympathetic overactivity and vagotomy increased renal-based hypertension. However, the role of the parasympathetic system in hypertension has not been investigated. This subject was investigated following subarachnoid hemorrhage (SAH). A total of 24 rabbits were used: control group (n = 5), SHAM group (n = 5), and an SAH group (n = 14; bolus injection of blood into the cisterna magna). Blood pressures were examined before, during, and after the experiment. After 3 weeks, animals were decapitated under general anesthesia. Vagal nodose ganglion, axonal degeneration, and renal artery vasospasm (RAV) indexes of all animals were determined histopathologically. Significant degenerative changes were detected in the vagal axons and nodose ganglia following SAH in animals with severe hypertension. The mean degenerated neuron density of nodose ganglions, vasospasm index (VSI) values of renal arteries of control, SHAM, and study groups were estimated as 9.0 ± 2.0 mm, 1.87 ± 0.19; 65.0 ± 12.0 mm, 1.91 ± 0.34; and 986.0 ± 112.0 mm, 2.32 ± 0.89, consecutively. Blood pressure was measured as 94.0 ± 10.0 mmHg in control group, 102.0 ± 12.0 mmHg in SHAM; 112.0 ± 14.0 mmHg in middle (n = 9); and >122.0 ± 10.0 mmHg in severe RAV-developed animals (n = 5). Differences VSI values and blood pressure between groups were statistically significant (P < 0.05). The degeneration of vagal nodose ganglion has an important role in RAV and the development of RAV and hypertension following SAH.

Describing a New Mechanism of Retinal Detachment Secondary to Ophthalmic Artery Vasospasm Following Subarachnoid Hemorrhage: An Experimental Study.

The pterygopalatine ganglion (PPG) and ophthalmic arteries (OpAs) have important roles in ocular autoregulation and retinal and visual functions. The relationship between PPG neuron density, OpA vasospasm, and retinal detachment in subarachnoid hemorrhage (SAH) has never been studied. This study was conducted on 25 rabbits. Five animals were in the control group (GI; n = 5), five in the sham group (GII; n = 5), and 15 in the study group (GIII; n = 15). After injection of 1 cc serum saline into the cisterna magna in the sham group, and autologous blood in the SAH group, the animals were followed for 3 weeks. All animals underwent a retinal examination five times a week for 3 weeks before and after the experiment. After the experiment, the neuron density of PPGs of the facial nerves, vasospasm index (VSI) of OpAs, and total basal surface values of the detached retinal parts (DRPs) were calculated. In the funduscopic examination, intravitreous hemorrhage ( Terson's syndrome) was detected in four animals in the SAH group. In the control groups, neuron density was 12,000 ± 1,240/mm3, VSI = 0.345 ± 0.076, and DRP = 0 to 1.5 mm2. Mean neuron density was 9,450 ± 940/mm3, VSI = 1.645 ± 0.940, and DRP = 6.23 ± 1.61 mm2 in the sham group (p < 0.05). Neuron density was 6,890 ± 932/mm3, VSI = 2.92 ± 0.97, and DRP = 9.43 ± 2.54 mm2 in SAH group. Mean neuron density, VSI of OpAs, and DRP values differed statistically significant between the SAH group and other groups (p < 0.005). There is an inverse relationship between PPG neurons and DRP. However, a direct relationship was observed between the mean VSI and DRP values.

Effect of Vasa Vasorum on Basilar Artery Vasospasm Following Subarachnoid Hemorrhage

A well-documented association exists between the vasa vasorum and vasopathologies, including atherosclerosis. However, information on the role of the vasa vasorum during vascular degenerative changes of vasospasm after subarachnoid hemorrhage (SAH) is insufficient. In this study, 34 rabbits were divided into 3 groups: basal group (N= 8), sham group (N= 8), and SAH group (N= 18). Experimental SAH was formed using a double-injection model. During follow-up, the neurologic status of the rabbits was observed. All rabbits were euthanized after 2 weeks, and the vasopathologic degeneration was categorized as normal, mild, moderate, and severe according to the changes in the basilar arteries. The numbers, locations, and spasms of the vasa vasorum and their relation to the vasodegenerative changes of the basilar artery were investigated. The basilar arteries were graded as normal in the basal and sham groups. In the SAH group, 6 rabbits had mild, 7 had moderate, and 5 had severe degeneration. Neurologic deficits were prominent in the SAH group, and deficit grades correlated with vascular degeneration. The number of the vasa vasorum were significantly higher in the SAH group, and an enhanced formation of the vasa vasorum was noted in which severe degenerative changes were present. Moreover, the vasospasm index of the vasa vasorum, which increased with the aggravation of vascular degenerative changes, was significantly higher in the SAH group. The vasa vasorum and their vasospasm play a crucial role in the pathogenesis of basilar artery degeneration in the vasospasm following SAH.

Reconsideration of Neurogenic Pulmonary Edema as Source of Metastatic Cerebral Abscess Following Subarachnoid Hemorrhages: A Preliminary Study

Subarachnoid hemorrhage (SAH) may be a cause of neurogenic pulmonary edema (NPE). It is well known that lymphatic fluid draining by thoracic duct to lungs consists of many dangerous metabolites, degraded tissue particles, and microbiologic pathogens. However, not enough studies have investigated whether NPE causes septicemia or not. In this study, we retrospectively examined our experimental materials to determine whether there is a meaningful relationship between NPE and cerebral abscess formation. Forty-two rabbits were divided into 3 groups: Control (n= 5), SHAM (n= 7), and SAH (n= 30) with severe neurogenic lung edema detected in rabbits. The SHAM and SAH groups received 1 mL saline and 1 mL autologous arterial blood into the Sylvian cisterna, respectively. Weight, heartbeat, respiration rate, and blood pressure were recorded by routinely using monitoring devices. All multilevel lungs and brain tissue microsections were examined by stereologic and Cavalier methods. For statistical analysis, NPE criteria and the numbers of abscess or abscess resembling cores in the brains were estimated in all groups and compared. The Mann Whitney-U test was used to analyze the results statistically. All rabbits were around 4 years old; body weight was between 3.94 and 4.5 kg; normal heart rhythm rate was found between 251 ± 39/minutes and 281 ± 30/minutes; and respiration rate was between 24 ± 5/minutes and 36 ± 7/minutes. Histopathologic examinations showed that abscess formations frequently spread in middle cerebral arterial territories of all animals in the NPE-detected rabbits. While average abscess numbers were estimated as 3 ± 1 in 7 animals (n= 7; P < 0.005) in severe NPE-detected rabbits, only 1± 1 abscess core was detected in a less severe NPE that developed in 3 (n= 3; P < 0.05) animals. The vasospasm index values of pulmonary arteries (PAs) of all animals were 1.233 ± 0.065 in the control group; 1.567± 0.0430 in the SHAM group, and 2.890 ± 0.0453 in the SAH group (P < 0.05). This experimental study showed that NPE is a relatively common pathology following experimental SAH in rabbits. The NPE is frequently complicated with brain abscess as shown in this study. The pathophysiologic mechanism was concluded, as NPE may be responsible for cerebral abscess development via bacteria/cytotoxic particles conveyed by thoracic duct to lungs and transferred from the ruptured alveoli-capillary membrane to the brain by way of systemic circulation.

Rational Roots of Sympathetic Overactivity by Neurogenic Pulmonary Edema Modeling Arising from Sympathyco-Vagal Imbalance in Subarachnoid Hemorrhage: An Experimental Study

Autonomous innervations of the lungs are maintained by cervical sympathetic and vagal nerves. Sympathetic overactivity-induced neurogenic pulmonary edema (NPE) is known as a serious complication of subarachnoid hemorrhage, but the rational neuronal mechanism of that overactivity has not yet been clarified fully. The aim of this study was to examine whether there is a relationship between vagal nerve ischemia related sympathetic overactivity and neurogenic pulmonary edema in subarachnoid hemorrhage. This study was conducted on 27 rabbits. A control group was formed of 5 animals, a sham group of 7 to which saline was administered, and a study group of 15 animals that were injected with homologous arterial blood into the cisterna magna. Electrocardiography and respiratory rhythm parameters were monitored for 3 weeks and the animals were then decapitated. Statistical analysis was made of the numbers of degenerated axons in the pulmonary branches of the vagal nerves, the neuron density of stellate ganglions and the vasospasm index of the pulmonary arteries. In the control group, the normal respiration rate was 34 ± 6 bpm, total axon number was 1600 ± 270/mm(2), degenerated axon number was 10 ± 3/mm(2), and vasospasm index was 1.34 ± 0.25. The sham group values were 30 ± 3 bpm, 163 ± 47/mm(2), and 1.95 ± 0.45 and the study group values were 45 ± 8 bpm, 530 ± 92/mm(2), and 2.76 ± 0.83. The mean stellate ganglion neuron density was evaluated as 8.112 ± 1.230/mm(3) in all animals, as 7.420 ± 4.10/mm(3) in animals with slight NPE, and as 12.512 ± 1.236/mm(3) in animals that developed severe NPE. High neuron density of stellate ganglion may have important roots in sympathetic overactivity-related NPE development in subarachnoid hemorrhage.

Uncovering a New Cause of Obstructive Hydrocephalus Following Subarachnoid Hemorrhage: Choroidal Artery Vasospasm–Related Ependymal Cell Degeneration and Aqueductal Stenosis—First Experimental Study

Hydrocephalus is a serious complication of subarachnoid hemorrhage (SAH). Obstruction of the cerebral aqueduct may cause hydrocephalus after SAH. Although various etiologic theories have been put forward, choroidal artery vasospasm-related ependymal desquamation and subependymal basal membrane rupture as mechanisms of aqueductal stenosis have not been suggested in the literature. This study was conducted on 26 hybrid rabbits. Five rabbits were placed in a control group, 5 were placed in a sham group, and the remaining rabbits (n= 16) were placed in the SAH group. In the first 2 weeks, 5 animals in the SAH group died. The other 21 animals were decapitated after the 4-week follow-up period. Choroidal artery changes resulting from vasospasm, aqueduct volume, ependymal cell density, and Evans index values of brain ventricles were obtained and compared statistically. Mean aqueduct volume was 1.137 mm(3) ± 0.096, normal ependymal cell density was 4560/mm(2) ± 745, and Evans index was 0.32 ± 0.05 in control animals (n= 5); these values were 1.247 mm(3) ± 0.112, 3568/mm(2) ± 612, and 0.34 ± 0.15 in sham animals (n= 5); 1.676 mm(3) ± 0.123, 2923/mm(2) ± 591, and 0.43 ± 0.09 in animals without aqueductal stenosis (n= 5); and 0.650 mm(3) ± 0.011, 1234/mm(2) ± 498, and 0.60 ± 0.18 in animals with severe aqueductal stenosis (n= 6). The choroidal vasospasm index values were 1.160 ± 0.040 in the control group, 1.150 ± 0.175 in the sham group, 1.760 ± 0.125 in the nonstenotic group, and 2.262 ± 0.160 in the stenotic group. Aqueduct volumes, ependymal cell densities, Evans index, and choroidal artery vasospasm index values were statistically significantly different between groups (P < 0.05). Ependymal cell desquamation and subependymal basal membrane destruction related to choroidal artery vasospasm may lead to aqueductal stenosis and hydrocephalus after SAH.

Vagal Ischemia Induced Lung Immune Component Infarct Following Subarachnoid Hemorrhage: An Experimental Study.

Neurogenic pulmonary edema (NPE) is the most serious complication of subarachnoid hemorrhage (SAH). As vagal nerves have vital roles in lung functions, vagal ischemia may have a causative role in the pathogenesis of NPE. We examined whether there was a relationship between vagal complex ischemia and lung immune complexes occupying the lymph node infarct in SAH. Thirty-two rabbits were divided into three groups: Control (n=5), SHAM (n=5) and SAH group (n=22). SAH was created by autologous blood injection into the cisterna magna and followed-up for 3 weeks. Vasospasm index (VSI) was defined as the ratio of the lung lymph node arteries (LLNA) wall section (wall ring) surface to the lumen surface. Degenerated axon numbers of vagal nerves, neuron densities of the nodose ganglion (NG) and VSIs of LLNA were compared for all groups. The mean degenerated vagal nerve axon density, neuron density of NG, and VSI of LLNA were 26±8/mm < sup > 2 < /sup > , 30±5/mm < sup > 3 < /sup > , and 0.777±0.048 in the control group; 1300±100/mm2, 720±90/mm < sup > 3 < /sup > , and 1.148±0.090 in the animals with slight vasospasm (n=12); and 7300±530/mm < sup > 2 < /sup > , 5610±810/mm3, and 1.500±0.120 in the animals with severe vasospasm (n=10), respectively. Degenerated vagal axon and NG neuron density may be a causative factor in the development of LLNA vasospasm induced lymph node infarct in SAH. Lung lymph node infarct may be an important factor in the prognosis of NPE.

Unraveling of the Effect of Nodose Ganglion Degeneration on the Coronary Artery Vasospasm After Subarachnoid Hemorrhage: An Experimental Study

Cardiac arrest is a major life-threatening complication of subarachnoid hemorrhage (SAH). Although medullary cardiocirculatuar center injury and central sympathetic overactivity have been suspected of initiating coronary artery spasm-induced cardiac arrest, we aimed to elucidate the effects of vagal ischemia at the brainstem on coronary vasospasm and sudden death in SAH. Twenty-six rabbits were randomly divided into 3 groups. Control (n = 5); SHAM (n = 8), and SAH group (n = 13). Experimental SAH was applied by injecting homologous blood into the cisterna magna, and the SHAM group was injected with isotonic saline solution also in the cisterna magna., Twenty-one days after the injection, histopathologic changes of the neuron density of nodose ganglia, the vasospasm index values of the coronary arteries, and the electrocardiographic events were analyzed. Increased vasospasm index of the coronary arteries and degenerated neuron density of nodose ganglion were significantly different between animals with SAH, control, and SHAM groups (P < 0.005). If neurons of the nodose ganglia are lesioned due to ischemic insult during SAH, the heart rhythm regulation by vagus afferent reflexes is disturbed. We found that there is causal relationship between nodose ganglion degeneration and coronary vasospasm. Our finding could be the reason that many cardiac events occur in patients with SAH. Vagal pathway paralysis induced by indirect sympathetic overactivity may trigger coronary vasospasm and heart rhythm disturbances. Our findings will aid in the planning of future experimental studies and in determining the clinical relevance of such studies.

Preventive Role of Hilar Parasympathetic Ganglia on Pulmonary Artery Vasospasm in Subarachnoid Hemorrhage: An Experimental Study.

Pulmonary arteries are mainly innervated by sympathetic vasoconstrictor and parasympathetic vasodilatory fibers. We examined whether there is a relationship between the neuron densities of hilar parasympathetic ganglia and pulmonary vasospasm in subarachnoid hemorrhage (SAH). Twenty-four rabbits were divided into two groups: control (n=8) and SAH (n=16). The animals were observed for 20 days following experimental SAH. The number of hilar parasympathetic ganglia and their neuron densities were determined. Proportion of pulmonary artery ring surface to lumen surface values was accepted as vasospasm index (VSI). Neuron densities of the hilar ganglia and VSI values were compared statistically. Animals in the SAH group experienced either mild (n=6) or severe (n=10) pulmonary artery vasospasm. In the control group, the mean VSI of pulmonary arteries was 0.777±0.048 and the hilar ganglion neuron density was estimated as 12.100±2.010/mm < sup > 3 < /sup > . In SAH animals with mild vasospasm, VSI=1.148±0.090 and neuron density was estimated as 10.110±1.430/mm < sup > 3 < /sup > ; in animals with severe vasospasm, VSI=1.500±0.120 and neuron density was estimated as 7.340±990/mm < sup > 3 < /sup > . There was an inverse correlation between quantity and neuron density of hilar ganglia and vasospasm index value. The low numbers and low density of hilar parasympathetic ganglia may be responsible for the more severe artery vasospasm in SAH.

Effect of hyperbaric oxygen therapy on cerebral vasospasm: a vascular morphometric study in an experimental subarachnoid hemorrhage model

This study was undertaken to investigate the preventive or therapeutic effect of hyperbaric oxygen therapy (HBOT) on cerebral vasospasm following experimental subarachnoid hemorrhage (SAH). Twenty rabbits were assigned randomly to one of four groups. Animals in Group I were not subjected to SAH or sham operation (control group, n = 5). Animals in Group II were subjected to sham operation and received no treatment after the procedure (sham group, n = 5). Animals in Group III were subjected to SAH and received no treatment after SAH induction (SAH group, n = 5). Animals in Group IV were subjected to SAH and received five sessions of HBOT at 2.4 atmospheres absolute (ATA) for 2 h (treatment group, n = 5). Animals were euthanized by perfusion and fixation 72 h after procedures. Basilar artery vasospasm indices, arterial wall thicknesses, and cross-sectional luminal areas were evaluated. Statistical comparisons were performed using Kruskal–Wallis and Mann–Whitney U tests. Mean basilar artery vasospasm index in the treatment group was significantly smaller than in the SAH group. Mean basilar artery wall thickness in the treatment group was significantly smaller than in the SAH group. Mean basilar artery cross-sectional luminal area in the treatment group showed an increase relative to the SAH group, but this difference remained statistically insignificant. Our results demonstrated that repeated application of HBOT at 2.4 ATA for 2 h attenuated vasospastic changes such as increased vasospasm index and arterial wall thickness. HBOT is thus a promising candidate for SAH-induced vasospasm. Further studies are needed to evaluate maximal effect and optimal application regimen.