Natural Cerebral Aneurysm and Spontaneous Subarachnoid Hemorrhage in Mammals Other Than Man: Is There a Scope for Comparative Medicine?

BACKGROUND: Concepts that showed substantial efficacy in animal models of subarachnoid hemorrhage (SAH) often failed to improve outcome in humans with aneurysmal SAH. The concept of "comparative medicine," an open-minded comparison across species, might offer an alternative to the "constructed" animal models' approach. Naturally occurring diseases in animals might bear more similarity to human diseases than models. In this context, the question arises whether spontaneous intracranial aneurysms exist in animals or not, and whether they cause SAH or not. METHODS: A systematic literature search was performed. Only articles dealing with natural aneurysms and/or SAH of mammals other than man were included. All articles dealing with induced aneurysms and/or SAH were removed. RESULTS: Of 2812 screened articles, 9 articles describing natural intracranial aneurysms and/or SAH were found. In total 1979 individual animals of 29 species were examined. Natural intracranial aneurysms were described in 7 individual animals of 6 species. Spontaneous SAH was described in 3 species. In 1 chimpanzee, a ruptured intracranial aneurysm caused an SAH. Histological descriptions of the aneurysms were strikingly similar to those of humans. CONCLUSIONS: Although interesting and innovative, the concept of "comparative medicine" seems to be impracticable due to the seemingly ultralow incidence of natural aneurysmal SAH in mammals other than man. The answer to the question "why intracranial aneurysms are less common in animals despite the strong histological similarity of cerebral arteries" might be a key issue. Last but not least, primates likely matter in SAH-related research, as aneurysmal SAH occurs in primates.

Investigating the efficacy of a new intravenous (IV) nanoemulsified sevoflurane/arginine formulation for maintenance of general anesthesia for embolization of cerebral aneurysm.

The aim of this research investigation was to profound analysis the mitigating impact of sevoflurane/arginine post-molding on cerebral ischemia-reperfusion damage in rats. The authors fabricated emulsions fusing sevoflurane, perfluorooctyl bromide as a settling specialist, and mixes of arginine polymer. Cell suitability and gene expression of tubulin and NeuN were assessed. The stability, morphology and functional group were evaluated utilizing dynamic light scattering (DLS), Transmission Electron Microscope (TEM), atomic force microscopy (AFM), and Fourier-transform infrared spectroscopy (FTIR). Cerebral aneurysms were prompted through hypertension and a solitary stereotactic infusion of elastase into the basal storage in rat. The capacity of the emulsions to decreased cerebral aneurysm was tried in vivo by regulating them IV delivery of Se/Arg samples to rats. Se/Arg pre-conditioning expanded cell feasibility in neuroblast (SK-N-DZ) cells. Se/Arg pre-conditioning diminished infarct volume and enhanced neurological result in rats subjected to cerebral hypoxia-ischemia. Se/Arg preconditioning expanded levels of tubulin and NeuN. The prepared sevoflurane/arginine material pre-conditioning-incited neuroprotective impacts in vitro as well as in vivo analyses. Sevoflurane/arginine post-molding decreased cerebral tissue misfortune detected 7 days after cerebrum hypoxia-ischemia. This impact was prompted by clinically significant focuses and canceled by Sevoflurane/arginine. These outcomes recommend that Sevoflurane/arginine post-conditioning ensures neonatal cerebrum against cerebrum hypoxia-ischemia.

Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation.

OBJECTIVE: Although elevated hemodynamics has been speculated to play a key role in intracranial aneurysm (IA) initiation, little is known about the specific hemodynamic microenvironment that triggers aneurysmal vascular degradation. We previously demonstrated maladaptive remodeling characteristic of IA initiation occurring in hemodynamic regions of combined high wall shear stress (WSS) and high WSS gradient near the apex of an experimentally created carotid bifurcation. This study examines whether this remodeling recapitulates the molecular changes found in IAs and whether molecular changes also correspond to specific hemodynamic environments. METHODS: De novo bifurcations were surgically created using both native common carotid arteries in each of 6 dogs. Bifurcations were imaged 2 weeks or 2 months after surgery by high-resolution 3-dimensional angiography, from which flow fields were obtained by computational fluid dynamics simulations. Subsequently, harvested tissues, demonstrating early aneurysmal changes near the apex, were immunostained for interleukin-1beta, endothelial and inducible nitric oxide synthases, nitrotyrosine, and matrix metalloproteinase-2 and -9. Spatial distributions of these molecules were comapped with computational fluid dynamics results. RESULTS: The aneurysmal wall showed decreased endothelial nitric oxide synthase expression compared with surrounding segments, the feeding artery, and native controls, whereas all other markers increased. Anti-CD68 staining indicated the absence of inflammatory cells in the aneurysmal wall. Comapping molecular marker distributions with flow fields revealed confinement of these molecular changes within the hemodynamic region of high WSS and high, positive WSS gradient. CONCLUSION: Aneurysm-initiating remodeling induced by combined high WSS and high, positive WSS gradient is associated with molecular changes implicated in IAs.

Tenascin-C-coated platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model.

OBJECT: Detachable platinum coils are widely used in the endovascular treatment of intracranial aneurysms. The use of coil placement produces a higher incidence of aneurysm recurrence compared with surgical clipping. To reduce the incidence of recurrence by promoting clot organization, the authors designed a platinum coil coated with tenascin-C (TNC), an extracellular matrix glycoprotein, and then histologically examined tissue responses. METHODS: Platinum coils were prepared by successive coatings with cationic polyethyleneimine and anionic heparin and then TNC or basic fibroblast growth factor (bFGF) was immobilized by affinity binding to the heparin. Six unmodified, six heparin-coated, six bFGF-coated, or eight TNC-coated platinum coils were inserted into ligated common carotid arteries (CCAs) of adult male rats, and CCA segments were harvested after 14 or 28 days. The percentages of organized areas occupying the luminal cavity in unmodified, heparin-coated, bFGF-coated, and TNC-coated groups were 4.8 +/- 4.6, 1.6 +/- 1.1, 17.9 +/- 10.7, and 93.4 +/- 6.9%, respectively. In addition, the mean lumen size in the TNC-coated group (0.35 +/- 0.23 mm2) was reduced to less than half that of the unmodified group (0.72 +/- 0.21 mm2). Immunohistochemical analysis revealed that alpha-smooth muscle actin-positive cells were a major cellular component of the organized tissue within the TNC-coated coils but not in the bFGF group. Collagen fibrils in the organized areas were also much thicker and denser with TNC-coated coils than with bFGF-coated coils. CONCLUSIONS: Placement of TNC-coated coils can remarkably accelerate organization of luminal cavities and reduce their volume, providing improved efficacy of these coils for endovascular embolization.

A triple bifurcation aneurysm model for evaluating complex endovascular therapies in dogs.

OBJECT: Animal aneurysm models are required for the study of the hemodynamics and pathophysiology of intracranial aneurysms in humans and so that experimental treatments can be tested prior to clinical trials. The authors developed a canine model that consistently produces up to three bifurcation aneurysms similar in morphological features and hemodynamics to human intracranial aneurysms. METHODS: In 10 mongrel dogs, a harvested segment of the external jugular vein was anastamosed to an external carotid artery (CA)-lingual artery bifurcation arteriotomy site to create a lateral bifurcation aneurysm. The surgery was repeated on the contralateral side in each animal to form a second lateral bifurcation aneurysm and, in five dogs, a CA-CA crossover anastomosis was also performed to create a terminal bifurcation aneurysm. Nineteen of 20 lateral bifurcation aneurysms were confirmed in 10 dogs by diagnostic angiography 7 to 14 days after surgery. Aneurysm fundus-to-neck ratios ranged from 1 to 2, depending on the size of the arteriotomy. The terminal bifurcation aneurysms were confirmed in all five dogs by diagnostic angiography 7 to 14 days after the procedure. The authors later tested endovascular techniques for embolizing the aneurysms. CONCLUSIONS: Three bifurcation aneurysms of sufficient size for endovascular access can be created in a reproducible fashion in the same animal. This model is useful for studying complex endovascular procedures in aneurysms that mimic the human condition and for testing new devices and techniques.

Histopathologic changes in oculomotor nerve and ciliary ganglion in aneurysmatic compression injuries of oculomotor nerve.

BACKGROUND: Bilateral common carotid artery ligation (BCCAL) increases vertebrobasilar blood flow and leads to increased luminal pressure, luminal enlargement, wall thinning, convolutions and sometimes aneurysm formation in posterior circulation arteries, especially the posterior communicating arteries (PcomA). PcomA aneurysms compress the oculomotor nerves. The principal aim of this investigation is to examine the histopathologic results of the compressive effect of PcomA aneurysms on the oculomotor nerves (OMN) and on ciliary ganglions (CG). METHODS: When we observed the effects of BCCAL on the posterior circulation arteries of the brain in fifteen ligated rabbits after sacrifice, we noticed aneurysm formation on these arteries in three rabbits. These aneurysms developed on the PcomAs compressed the oculomotor nerves. These compressed nerves and normal oculomotor nerves together with their ciliary ganglions were examined histopathologically. RESULTS: A PComA aneurysm developed in three rabbits from 15 ligated animals and these aneurysms compressed the oculomotor nerves on the same side. Partial peripheral necrosis and axonal loss were seen on the compressed oculomotor nerves. Concomitantly, cellular loss and necrosis were also observed on their ganglions. CONCLUSION: Bilateral common carotid artery ligation may lead to PcomAs and these aneurysms could compress the oculomotor nerves. Compression injuries of oculomotor nerve may cause cellular injury and necrosis on both oculomotor nerves and ciliary ganglions.

Anisocoria and middle cerebral artery saccular (berry) aneurysm in a rhesus macaque (Macaca mulatta).

A 27-year-old female rhesus macaque (Macaca mulatta) developed anisocoria. The left pupil was dilated and unresponsive to light. The macaque was euthanized because of unrelated reasons and the body was submitted for necropsy. On gross examination, a berry aneurysm of the right middle cerebral artery causing marked compression of the right optic tract was found. Arteriosclerotic changes were observed microscopically in the right middle cerebral and in the internal carotid arteries. The left iris was markedly degenerated, with atrophy of the constrictor muscle. Compression of the right optic tract may cause homonimus hemianopsia. A dilated and unresponsive left pupil indicated a lesion in the ipsilateral parasympathetic efferent pathway. In the absence of appreciable lesions of the left oculomotor nerve, the most likely cause of mydriasis was the iridic lesion. Intracranial aneurysms are common in humans (2 to 5%), but not in other species. Only about 10% of unruptured aneurysms are associated with neurologic deficits related to mechanical compression, such as visual deficits or anisocoria. Meticulous investigation of the ocular vascular and neural pathways led us to conclude that the anisocoria was unrelated to the aneurysm. To our knowledge, this report represents the first documented case of a naturally occurring intracranial aneurysm in nonhuman primates.

Carotid and cerebral angiography in the horse.

Carotid and cerebral angiography has been found to be a relatively simple technique to carry out in the horse. At most it involves a cutdown approach to the carotid artery, followed by catheterisation of the artery and selective catheterisation, if necessary, of one of its three branches. The technique can be carried out with standard equipment normally available within equine hospital facilities. The authors have employed angiography as a routine aid to diagnosis over the past nine years, without encountering any serious complications or adverse reactions. Carotid angiography has been especially valuable in the investigation of horses with guttural pouch mycosis. The technique has permitted the presence of aneurysms to be detected in many cases and significant vascular abnormalities in four cases. This information is valuable for the surgical treatment of horses with guttural pouch mycosis by ligation of the appropriate artery. Other indications for the use of carotid angiography include the investigation of ethmoidal haematoma, idiopathic Horner's syndrome, neoplasia of the head, venous aneurysms and arterial aneurysms in sites not associated with the guttural pouch. There are fewer occasions for the use of cerebral angiography in the horse, but it is indicated as an aid to the differential diagnosis of some abnormalities of the central nervous system.