Rat model of subarachnoid hemorrhage based on rese

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Based on rat model of subarachnoid hemorrhage

Of: Zhao Wei Jiang, Wu Tsung Hou, Liu Naiyou Abstract People use several means to simulate subarachnoid hemorrhage in the rat model to study the pathophysiological changes after SAH, brain damage and delayed cerebral vasospasm. However, to date no single model can fully simulate the clinically observed all the phenomena. The author reviewed the relevant experimental subarachnoid hemorrhage research literature on experimental model of subarachnoid hemorrhage caused by mold method, the method involves the content and conclusions of the research done in a summary to the model the scope of a brief assessment, and from the experimental rat model of SAH to build greater awareness of the SAH. Has been published author of the rat model of subarachnoid hemorrhage in a systematic review of related articles from Pubmed Medline search system, search keywords were + rats The author and research methods from To Die for the contents of a preliminary analysis of the literature. The results show that needs to be selected according to different experimental rat model corresponding. In some cases, you should use two or more model of subarachnoid hemorrhage in rats to clarify some mechanisms to achieve the closest to the clinical results, in order to clear experimental subarachnoid hemorrhage in rats in an important study effect. Analysis showed that the experiment needs to be selected according to different corresponding rat model, in some cases, you should use two or more model of subarachnoid hemorrhage in rats to clarify some mechanisms to achieve the closest to the clinical results . Key words Rat; subarachnoid hemorrhage; the cisterna magna injection; vascular puncture; cross before Infusion Experimental subarachnoid hemorrhage in rats 【Abstract】 Several means have been undertaken to simulate subarachnoid hemorrhage (SAH) in rats, in which pathophysiological changes, brain injury and vasospasm are investigated. However, no single means has been used to help interpret the whole phenomena observed clinically. By tracing back the published experimental data in rats, we endeavoured to come up with the optimal means corresponding to a certain clinical phenomenon. We performed a systematic review on published data about the SAH model in rats. Published articles were identified by searching Pubmed Medline. Assessment items were classified into Pathological evaluation; Vasospasm exploration; Behavioral investigation and survival; whether application in pharmaceutical filtration. Certain rat subarachnoid hemorrhage model should be purposefully selected according to certain experimental design. In some special circumstances, two or more rat SAH model should be combined to interpret a complete mechanism to achieve a good result. Two or more rat models should be used to better our understanding of a phenomenon. 】【Key words Rat; subarachnoid hemorrhage (SAH); cisterna magna injection; endovascular puncture; prechiasmatic injection subarachnoid hemorrhage-induced brain damage has been concerned about for years, but the exact mechanism of injury caused by SAH in basic and clinical [u] Medicine workers is still a huge challenge, and we inquire animal model was provided a platform for these mechanisms. In the past half century, people in the baboon,[link widoczny dla zalogowanych], monkey, rabbit, dog and rat SAH occurred on the part of the simulated phenomena appear [1, 5], the mechanism for the SAH provides a large amount of data. In all experimental animals, the rat model because of its cost-effective, the response can be relatively accurate and widely recognized subarachnoid hemorrhage. There are three more mature development of the rat SAH model: (1) blood injection model cistern (cisterna magna injection, CMI); (2) endovascular puncture model (endovascular puncture mod, EVP); (3) cross the blood before cell injection model (prechiasmatic cisterna injection, PCI). They are widely used in SAH secondary brain injury and pathological aspects of the pathophysiology and mechanisms of cerebral vasospasm great observation and research. However, as in species of rats and the remaining huge gap between the rat model of SAH in the reflection of the importance and which model is more superior to all become a serious problem. In view of this, the paper nearly 15 years Pubmed Medline rat SAH published research articles related to a small review. 1 method 1.1 Documents received inquiries and literature selection criteria were selected in August 1990 -2005 Pubmed Medline indexed been published on experimental rat subarachnoid bleeding papers, the search keywords as In addition, other limits include: (1) or for the use of autologous arterial blood were injected into the cisterna magna, or is caused by endovascular puncture model; (2) is only a single study in rats with subarachnoid hemorrhage, no involved in clinical research. 1.2 statistical correlation model number of the literature in three time periods: time period 1:1990-1995 years; time 2:1996-1999 years; time 3:2000-2005 years. Different time periods, respectively, using a different statistical model number and the relevant literature literature literature in the number of total percentage. 1.3 summarized from the research methods used, pathophysiology, injury mechanism and the mechanism of vasospasm induction angle. 1.4 overall evaluation of the results found by the search were from 1990-2005, Aug. eligible three related rat model of subarachnoid hemorrhage in the literature 146. From 1990-1995, the CMI, EVP, and the number of PCI in the literature were 29 (90.63%), 2 (6.25%) and 1 (3.13%); from 1996-1999, the number of relevant literature was 36 (80% ), 9 (20%) and 1 (2.23%), in which the relevant literature uses both PCI CMI law; and from 2000-2005, in August the number of the relevant literature into 36 (51.43%), 31 (44.29%) and 5 (7.14%), of which CMI PCI combined with the literature are two. 2 methods used for rat cisterna magna injection of autologous arterial blood was drawn from the femoral artery, autologous blood, the syringe or catheter through the atlanto-occipital fascia introduced into the blood cistern, and the head tilt in rats by a certain angle so that the blood in the subarachnoid spreading method. Note blood range 0.07 ~ 0.5ml [6 ~ 8], there is first out of certain cerebrospinal fluid, and injection, direct injection, injection speeds ranging from the 30s ~ 10min. Visual observation of blood is widely distributed in the underside of the temporal lobe brain tissue, Willis ring around the middle frontal lobe, cerebellum of the brain lobes, the brain stem before and after the department, we still observed by HE staining of blood through the fourth ventricle into the third ventricle and lateral ventricles. In addition, in order to be more cerebral vasospasm after SAH nearly two-phase characteristics of the human, people in a single cisterna magna injection of autologous blood on the basis of secondary and copy the rat cisterna magna injection of autologous arterial blood, that the first note 24h or 48h blood, autologous blood re-injected into the cisterna magna and cerebral vasospasm observation time was extended to SAH 7 days. Fig 1. Numbers of references about three widely recognized experimental models in rats embodied by medline from 1990 to August 2005, which are divided into 3 stages: stage1 1990-1995; stage 2 1996-1999; and stage 3 2000-August 2005.CM cisterna magna injection, EV endovascular puncture, and PC prechiasmatic injection. endovascular puncture model, also known as Sheffield (Sheffield model), and the middle cerebral artery suture method similar to the , about the nylon line through the external carotid artery, carotid artery from the middle cerebral artery and into the intersection before the artery and through the line further forward at the intersection of 2 ~ 3mm puncture, and then exit line to the external carotid artery, blood pressure into subarachnoid space under the action of widely distributed in the cerebral hemispheres base, convex, and interhemispheric subarachnoid and the ventricular system [9,10]. This method can cause vascular damage and sudden increase in intracranial pressure, better simulation of aneurysm rupture with subarachnoid hemorrhage caused by the situation, and severe brain damage, neurological deficit symptoms clear, but a higher mortality rate within 24h ( 50%) [10], and the varying degrees of damage for each rat, CBF decreased mortality level and there are differences. prechiasmatic pool syringe injection is inserted into the hole through the optic chiasm before the pool will be drawn from the femoral artery or axillary artery blood into the subarachnoid space to the distribution in the subarachnoid methods. Using this method arterial injection 0.3ml, mortality rate was 50% [11]. 3 levels of the pathophysiology 3.1 ECM cerebral blood flow changes very early after subarachnoid hemorrhage in the pathophysiology of indicators, is also an important indicator of evaluation of drug efficacy . CPP is the mean arterial pressure and intracranial pressure difference, Bederson [10] in the rat model of EVP CPP (cerebral perfusion pressure) and the relationship between CBF and found within the CPP decreased SAH 60s and reached its lowest point, then began to increase, while the CBF continued to decline, and later reached its lowest point in the CPP, and both changes are not correlated peak. These findings indicate that despite the decline in CPP after SAH caused the initial decline in cortical cerebral blood flow, but the CPP fell to the bottom after the other factors such as acute vasoconstriction continued to decline to participate in the CBF to [10]. Method for determination of cerebral blood flow with radioactive microspheres method, the hydrogen clearance method and laser Doppler method. Kehl et al [11] found that injecting blood cistern 0.3ml, 10min when the CBF decreased to 30% of normal, and continued low level 2h, and pretreated with 20-HETE block the formation of 17-ODYA and HET0016 can decrease the degree of CBF reduced by 40%, and blood flow in the fully restored after SAH induction 1h. Prunell [12] were used cistern, puncture and intravascular cross pool before the blood injection method to observe the CBF, which CBF decreased in the blood after injection to 35%. Note the blood in the cisterna magna within the CBF in the SAH 15min gradually increased and returned to normal levels, is not conducive to conduct a study on the acute phase of SAH. The vascular puncture, blood injection prechiasmatic pool CBF in SAH 90min law may be maintained at 60% and 89% of normal levels. Injecting blood into the cisterna magna SAH method of late has some value. Critchley GR and Zausinger [13,14] EVP method by ICP increases after subarachnoid hemorrhage found in up to (53.0 ± 9. 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mmHg, and associated with decreased cerebral blood flow, decreased to levels of oxidative the normal value (42.8 ± 7.7)%. Clozel [15] using radioactive microsphere method for rCBF monitoring found that injecting blood into the cisterna magna 0.3ml decreased cerebral blood flow can cause 22% to 38%, while the cisterna magna through the selective ETA receptor antagonist BQ-123 can be five peptide completely inhibited by SAH 60 ~ 120min during the decline in rCBF. Sun et al [16] also found in the EVP model of SAH can cause acute CBF decrease associated with ET-1 was significantly increased and continued to 24h. Naveri [17] found that the use of laser Doppler flowmetry, SAH 20min when intravenous angiotensin Ⅳ (angiotensin Ⅳ, ANG Ⅳ) in the SAH 60min when the CBF increased from 45% to 84%. Yamamoto [18] carried out using tracer 15O-H2O positron emission tomography showed injecting blood into the cisterna magna caused significantly decreased frontoparietal and occipital CBF, and Prophylactic AVS [(+/-)- N, N'- propylenedinicotinamide] can improve CBF. These tips SAH decreased cerebral blood flow and endothelin, angiotensin, hydroxyl radicals and activation of Ca2 + channels close. also continue to maintain blood levels of 30% at baseline significantly correlated with the inflammatory response, and the TUNEL positive area consistent with a high degree of inflammatory response. Nestin, ED1, OX6, and intercellular adhesion molecule and tumor necrosis factor showed a strong positive immune to spill the blood of the brain tissue near the reaction of the [19]. Prunell [20] studies have shown that using the EVP method and secondary acute CBF decrease the degree of cell death, suggesting the relevance of apoptosis-like pathway, indicating the existence of a therapeutic time window in order to have adequate treatment to reduce the ultimate damage caused by SAH . 3.2 intracranial pressure, brain water content, blood-brain barrier blood-brain barrier to maintain the integrity of the nervous system for a constant environment is very important. Many neurological diseases can cause changes in blood-brain barrier, including hypertension, infarction, brain trauma and a sudden increase in intracranial pressure [21]. Germanò application in a rat model of CMI 14C labeled α-amino isobutyric acid quantification studies have shown a clear SAH subarachnoid hemorrhage can cause damage [22], and that control to improve the treatment of subarachnoid hemorrhage BBB has a certain the clinical value, after using the Evans blue extravasation Germanò quantitative method that can improve the use of calpain inhibitors BBB, improve behavioral performance in rats SAH [23]. Then Gules blood injection in the CM model, the second study found that SAH 7 天 BBB permeability in rats appears to change, and consistent with the microvascular endothelial cells [24]. experimental subarachnoid hemorrhage increased intracranial pressure, BBB permeability and brain edema and cause high mortality. SAH cerebral artery induced phosphorylation of VEGF and MAPKs, followed by the cerebral cortex. The Src family inhibitor PP1 can reduce the BBB permeability, brain edema and mortality and to reduce phosphorylation of VEGF and MAPKs [25]. 3.3 Mechanisms of brain injury in recent years, as people apoptosis in-depth understanding and knowledge of anatomy and clinical pathology in the discovery of evidence relating to apoptosis, it is increasingly clear the cobwebs of apoptosis membrane hemorrhage under the mechanism of brain injury [26,27], people are using the rat SAH model to study brain tissue after SAH may be involved in apoptosis and related signal transduction pathway. Prunell [20] using two methods PCI EVP and tissue damage after SAH apoptotic mechanism was studied. The results showed that 1 / 3 to 2 / 3 of the surviving rats 7 days after SAH 2 and TUNEL staining brain slices DNA breakage. More than 80% TUNEL-positive cells into neurons, the majority of TUNEL-positive cells showed chromatin condensation and / or blister, and Bax immunostaining was enhanced. 50% of TUNEL-positive neurons in the activity of Caspase-3 staining, a small number of Bcl-2 staining. Acute cerebral blood flow reduced to 30% of the duration of the degree of TUNEL staining, suggesting that SAH may be largely caused by delayed cell death, but not all live animals. And secondary acute CBF decrease the extent of cell death, suggesting that class of SAH related apoptosis-like pathway, and there is a therapeutic window of time in order to take adequate treatment to reduce the ultimate damage after SAH.