Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

Intelligent Machine Learning Enabled Retinal Blood Vessel Segmentation and Classification

Automated segmentation of blood vessels in retinal fundus images is essential for medical image analysis.The segmentation of retinal vessels is assumed to be essential to the progress of the decision support system for initial analysis and treatment of retinal disease.This article develops a new Grasshopper Optimization with Fuzzy Edge Detection based Retinal Blood Vessel Segmentation and Classification(GOFED-RBVSC)model.The proposed GOFED-RBVSC model initially employs contrast enhancement process.Besides,GOAFED approach is employed to detect the edges in the retinal fundus images in which the use of GOA adjusts the membership functions.The ORB(Oriented FAST and Rotated BRIEF)feature extractor is exploited to generate feature vectors.Finally,Improved Conditional Variational Auto Encoder(ICAVE)is utilized for retinal image classification,shows the novelty of the work.The performance validation of the GOFEDRBVSC model is tested using benchmark dataset,and the comparative study highlighted the betterment of the GOFED-RBVSC model over the recent approaches.

Retinal thickness and fundus blood flow density changes in chest pain subjects with dyslipidemia

AIM:To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography(OCTA).METHODS:All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination.According to the serum lipid levels,the participants were divided into the control group and the dyslipidemia group.The retina thickness and fundus blood flow density were determined using OCTA.RESULTS:The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age-and sexmatched participants without dyslipidemia.The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior(P=0.004 and P=0.014,respectively)and temporal(P=0.015 and P=0.019,respectively)regions,both inner and outer layers.In terms of blood flow density in the macula or optic disk,there was a decreasing trend in the dyslipidemia group compared with the control group,especially in the inferior and temporal regions.CONCLUSION:Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density.Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.

The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells

Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.

Involvement of moesin phosphorylation in ischemia/reperfusion induced inner blood-retinal barrier dysfunction

AIM: To investigate the role of moesin and its underlying signal transduction in retinal vascular damage induced by retinal ischemia-reperfusion(RIR) insult.METHODS: C57 BL/6 mice were subjected to continued ischemia for 45 min, followed by blood reperfusion. The expression and phosphorylation of moesin in retinal vessels were detected by immunohistochemistry and Western blotting. The inner blood-retinal barrier was evaluated using FITCdextran leakage assay on whole-mount retina. Further studies were conducted to explore the effects of p38 mitogen-activated protein kinase(MAPK) pathway on the involvement of moesin in RIR-evoked retinal vascular hyperpermeability response. RESULTS: It revealed that RIR induced moesin phosphorylation in a time-dependent manner after reperfusion. The phosphorylation of moesin was alleviated by inhibitions of p38 MAPK, while this treatment also ameliorated the dysfunction of inner blood-retinal barrier. CONCLUSION: The results suggest that moesin is involved in RIR-evoked retinal vascular endothelial dysfunction and the phosphorylation of moesin is triggered via p38 MAPK activation.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2diabetes mellitus model

AIM： To examine the expression of high mobility group box-1（HMGB-1） and intercellular adhesion molecule-1（ICAM-1） in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier（BRB） and blood-brain barrier（BBB） in a rat model of type 2 diabetes.METHODS： The type-2 diabetes mellitus（DM） model was established with a high-fat and high-glucose diet combined with streptozotocin（STZ）. Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay（ELISA）.RESULTS： A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection（P 〈0.01）. The serum levels of fasting insulin,Insulin resistance homeostatic model assessment（IRHOMA）,total cholesterol（TC）, total triglycerides（TG） and low density lipoprotein cholesterol（LDL-C） in the DM rats significantly higher than those in the controls（all P 〈0.01）.HMGB-1（0.96±0.03, P 〈0.01） and ICAM-1（0.76±0.12, P 〈0.05） levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1（0.83±0.13, P 〈0.01） and ICAM-1（1.15 ±0.08, P 〈0.01） levels in the hippocampal tissues in the DM rats were alsosignificantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls（P 〈0.01）.However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats.CONCLUSION： BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.

Effect of pyridone agent on blood-retinal barrier in diabetic mice

AIM： To evaluate the therapeutic effect of fluorofenidone on disrupted blood-retinal barrier in the diabetic mice and uncover its underlying mechanism. METHODS： db/db mice were randomly chosen for treatment with daily doses of fluorofenidone or placebo at 5-week-old, treatment continued until mice reach 24-week- old. Then, expression of transcriptiona factor insulin gene enhancer binding protein-1 （Islet-I） and vascular endothelial growth factor （VEGF） in murine retinas were evaluated. Retinal vascular permeability was assessed by examining the level of albumin in db/db murine retinas. Furthermore, the retinal vessel tight junction was estimated by checking the level of occludin in the murine retinal tissues. RESULTS： After occurrence of diabetic retinopthy in db/ db mice, expressions of transcritpional factor Islet-1 was found to be upregulated in db/db murine retinas compared with non-diabetic controls. Similar to expression pattern of Islet-l, VEGF were also demonstrated to be increased in retinas of db/db mice, which was accompanied by increased retinal vascular leakage and decreased tight junction protein level. Systemetic administration of fluorofenidone repaired broken retinal vascular tight junction by restoring occludin expression in db/db retinal tissue. Consequently, retinal vascular premeability were indicated to be reduced by examining the transudative albumin level in diabetic retinal tissues. Both Islet-1 and VEGF expression were inhibited in the retinas of db/db mice after treatment with fluorofenidone. CONCLUSION： Fluorofenidone significantly protectes retinal tight junction and reduces retinal vascular leakage. The phenomenon can be partially attributed to reducing overexpression of Islet-1 and VEGF in diabetic retinal tissues.

Infl iximab relieves blood retinal barrier breakdown through the p38 MAPK pathway in a diabetic rat model

AIM： To clarify the mechanism of infliximab treatment in diabetic macular edema （DME） and to provide a new alternative therapy for DME. METHODS： Rats were randomly divided into the control group, the model group and the infliximab treatment group. A diabetic rat model was created. The concentration of TNF-α in the vitreous body was detected by ELISA. The expressions of B-Raf, p38, claudin-1 and occludin in the retina were detected by Western blot. The integrity of the blood retinal barrier （BRB） was measured using Evan＇s blue as a tracer. RESULTS： After three months and six months of the diabetes model, the vitreous TNF-α level in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant （at 3mo, F=857.098, P〈0.001; 6mo, F=1261.897, P〈0.001）. The retina B-Raf and p38 levels in the model group were higher than that of the control group. They were also higher in treated group than that of the control group but were lower than that of the model group. The differences among the three groups were statistically significant （B-Raf at 3mo, F=106.596, P〈0.001 and at 6mo, F=200.681, P〈0.001; p38 at 3mo, F=41.662, P〈0.001 and at 6mo, F=67.979, P〈0.001）. The retina claudin-1 and occludin levels in the model group were lower than that of the control group. They were also lower in treated group than that of the control group but were higher than that of the model group. The differences among three groups were statistically significant （claudin-1 at3mo, F=-139.088, P〈0.001 and at 6mo, F=128.415, P〈0.001; occludin at 3mo, F=-92.733, P〈0.001 and at 6mo, F--104.478, P〈0.001）. The retinal Evans blue leakage in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant （at 3mo, F=-447.946, P〈0.001; at 6mo, F＇=-1610.732, P〈0.001）. CONCLUSION： In-α diabetic rat model, infliximab may relieve TNF-α induced BRB breakdown via the B-Raf and p38 signaling pathway.

RNA interference targeting NOX4 protects visual function in an experimental model of retinal detachment by alleviating blood-retinal barrier damage

AIM:To observe the effects of the inhibition of NADPH oxidase 4(NOX4)expression on the retinal vascular barriers and visual function after retinal detachment(RD).METHODS:RD model was established 3 wk after adenoassocianed virus vector injection.The retinal tissue was harvested 3 d after RD,and the death of retinal vascular endothelial cells and photoreceptors was observed using electron microscopy.The NOX4 expression was detected by Western blot.Confocal microscopy was used to observe a retinal patch that had been perfused with Evans blue.A modified water maze test was used to detect the time required to find the platform on the water surface.The visual function of the rats was evaluated and reactive oxygen species(ROS)expression was detected by a fluorescence microplate reader.RESULTS:The retinal patch showed that NOX4 interference significantly reduced the destruction of the tight junctions between the retinal endothelium of RD rats and reduced leakage.Western blotting showed decreased expression of the NOX4 protein and decreased expression of ROS in retinal tissue;the Morris water maze test results showed that NOX4 interference significantly decreased the escape latency of the rats.CONCLUSION:NOX4 interference reduces the production of ROS in retinal vascular endothelial cells after experimental RD,thereby protecting the blood-retinal barrier and protecting visual function.

Therapeutic potential of iron chelators in retinal vascular diseases

Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energyintensive tissues in the body,the retina is susceptible to iron imbalance.The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species.This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis,eventually resulting in retinal dysfunction.The blood-retinaretinal barrier is eventually harmed by oxidative stress and elevated inflammation,which are characteristics of retinal vascular disorders.The pathophysiology of retinal vascular disorders may be significantly influenced by iron.Recently,iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating.Therefore,iron neutralization is considered to be a new and potentially useful therapeutic strategy.This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.

The importance of laminin at the blood-brain barrier

The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte endfeet.In addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell behavior.The extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior.In this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity.Finally,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.

Parafoveal retinal massage combined with autologous blood cover in the management of giant,persistent or recurrent macular holes

AIM:To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes(MHs)and present the surgical procedure.METHODS:Patients with giant(minimum diameter>800 pm),recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study.After surgery,all patients were informed to maintain a prone position for at least 7d.Preoperative and postoperative best-corrected visual acuities(BCVAs)were compared and MH closure rate was measured as the main outcome.RESULTS:A total of 13 MH patients consisted of 6 giant MHs,4 persistent holes and 3 recurrent holes(5 men and 8 women;average age was 56.40±11.72y)were enrolled in this study.MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed.Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed.No intraoperative complications were observed.BCVA improved from 1.73 IogMAR to 0.74 IogMAR at 6mo postoperation.There was significant difference in BCVA before versus after the surgery(P<0.05).There were no adverse events occurred during the follow-up period.CONCLUSION:With easier surgical procedure,parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.

Malfunction of outer retinal barrier and choroid in the occurrence and progression of diabetic macular edema

Diabetic macular edema(DME) is the most common cause of vision loss in diabetic retinopathy,affecting 1 in 15 patients with diabetes mellitus(DM).The disruption of the inner blood-retina barrier(BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris,in the occurrence and evolution of DME.The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition.In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.

Evans blue staining to detect deep blood vessels in peripheral retina for observing retinal pathology in early-stage diabetic rats

AIM: To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue(EB) perfusion, and utilize the modified whole-retina spreading method to make the slides while protecting the periphery of the retina. METHODS: The Sprague-Dawley(SD) rats were randomly divided into 6 groups. Each group named as the normal groups for 4, 8, and 12 wk and the diabetic groups for 4, 8, and 12 wk. The EB was injected into the cardiovascular system of the rats at the different time points. The retina of each group was obtained for observation.RESULTS: The superficial vascular leakage was found in all 6 groups. The size of leakage area of superficial retinal blood vessels was(0.54±0.23)%,(0.65±0.11)%,and(0.58±0.10)% in normal group. No notable leakage was found in the deep blood vessels [(0.03±0.04)%,(0.03±0.05)%, and(0.03±0.05)%]. The deep retinal vascular leakage was found in the peripheral retina of diabetic rats. The size of leakage area of superficial retinal blood vessels in diabetic group were(0.53±0.22)%,(0.69±0.16)%, and(0.52±0.11)%. The leakage areas of deep blood vessels were(0.54±0.50)%,(1.42±0.16)%, and(1.80±0.07)% at 4, 8, and 12 wk, respectively. There was a statistically difference of the leakage area between the 8 th week and the 4 th week of diabetes group(P=0.003). The statistically significant difference between the diabetes and the control groups was noted at 4 wk and 8 wk(P<0.001).CONCLUSION: The main retinal pathological changes of early-stage diabetic rats are the vascular leakage of the periphery of deep retina. Diabetic rats modeled after 8 wk have semi-quantitative statistical difference compared with the normal rats, thus early intervention treatment research can start at this time point.

RETINAL SPECTRAL IMAGING AND BLOOD FLOW MEASUREMENT

Measurement of both oxygen saturation and blood flow in the retinal vessels has proved to give important information about the eye health and the onset of eye pathologies such as diabetic retinopathy.In this study,we present the implementation,on a commercially available fundus camera,of a retinal imager and a retina blood flow velocimeter.The retinal imager uses division of aperture to acquire nine wavelength-dependent sub-images of the retina.Careful consideration is taken to improve image transfer by measuring the optical properties of the fundus camera and modeling the optical train in Zemax.This part of the setup is calibrated with optical phantoms of known optical properties that are also used to build a lookup table(LUT)linking phantom optical properties to measured reflectance.The retina blood flow velocimeter relies on tracking clusters of erythrocytes and uses a fast acquisition camera attached to a zoom lens,with a green illumination LED-engine.Calibration is provided using a calibrated quartz capillary tube and human blood at a known flow rate.Optical properties of liquid phantoms are retrieved from measured reflectance using the LUT,and blood flow measurements in the retina are presented.

Effect of 0. 2 % Brimonidine on Retinal Blood Flow

Purpose: To analyze the effect of 0.2 % brimonidine eye drops on retinal blood flow of patients with glaucoma. Methods: Using self-control method and Heidelberg Retina Flowmeter (HRF), we examined the volume, flow and velocity of the superior nasal and temporal, the inferior nasal and temporal artery of retina at baseline and 2 hours after single instillation of 0.2% brimonidine. Results: There were no significant changes in volume, fio~ and velocity of four vessels betore and after the administration of 0.2 % brimonidine. Conclusions: There are no significant ocular haemodvnamic benefits associated with Brimonidine therapy to the glaucoma patients. Eye Science 2001; 17:42 ～ 45.

Multimodal imaging in acute retinal ischemia: spectral domain OCT, OCT-angiography and fundus autofluorescence

AIM： To describe retinal findings of various imaging modalities in acute retinal ischemia. METHODS： Fluorescein angiography（FA）, spectral domain optical coherence tomography（SD-OCT）, OCTangiography（OCT-A） and fundus autofluorescence（FAF） images of 13 patients（mean age 64y, range 28-86y） with acute retinal ischemia were evaluated. Six suffered from branch arterial occlusion, 2 had a central retinal artery occlusion, 2 had a combined arteriovenous occlusions, 1 patient had a retrobulbar arterial compression by an orbital haemangioma and 2 patients showed an ocular ischemic syndrome.RESULTS： All patients showed increased reflectivity and thickening of the ischemic retinal tissue. In 10 out of 13 patients SD-OCT revealed an additional highly reflective band located within or above the outer plexiform layer. Morphological characteristics were a decreasing intensity with distance from the fovea, partially segmental occurrence and manifestation limited in time. OCT-A showed a loss of flow signal in the superficial and deep capillary plexus at the affected areas. Reduced flow signal was detected underneath the regions with retinal edema. FAF showed areas of altered signal intensity at the posterior pole. The regions of decreased FAF signal corresponded to peri-venous regions. CONCLUSION： Multimodal imaging modalities in retinal ischemia yield characteristic findings and valuable diagnostic information. Conventional OCT identifies hyperreflectivity and thickening and a mid-retinal hyperreflective band is frequently observed. OCT-A examination reveals demarcation of the ischemic retinal area on the vascular level. FAF shows decreased fluorescence signal in areas of retinal edema often corresponding to peri-venous regions.

Statins Protect the Blood Brain Barrier Acutely after Experimental Intracerebral Hemorrhage

Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was induced in 27 male Wistar rats by stereotactic injection of100mL of autologous blood into the striatum. Rats were divided into three groups (n = 9/group): 1) oral treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin, or 3) phosphate buffered saline daily starting 24-hours post-ICH and continuing daily for the next 3 days. On the fourth day, the animals underwent magnetic resonance imaging (MRI) for measurements of T1sat (a marker for BBB integrity), T2 (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed and immunohistology or Western blotting was performed. Results: MRI data for animals receiving simvastatin treatment showed significantly reduced BBB dysfunction and improved CBF in the ICH rim compared to controls (P 0.05) 4 days after ICH. Simvastatin also significantly reduced edema (T2) in the rim at 4 days after ICH (P 0.05). Both statin-treated groups demonstrated increased occludin and endothelial barrier antigen levels within the vessel walls, indicating better preservation of BBB function (P 0.05) and increased number of blood vessels (P 0.05). Conclusions: Simvastatin treatment administered acutely after ICH protects BBB integrity as measured by MRI and correlative immunohistochemistry. There was also evidence of improved CBF and reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend by MRI measurement.

Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

BACKGROUND： The integrity of the blood brain barrier （BBB） plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 （MMP-9） is closely related to cerebral ischemia/reperfusion injury OBJECTIVE： This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability. DESIGN, TIME AND SETTING： This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006. MATERIALS： Ninety healthy male SD rats, aged 3-4 months, weighing 200-280 g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody （Boster, Wuhan, China） and Evans blue （Sigma, USA） were also used. METHODS： All rats were randomly divided into 9 groups with 10 rats in each group： normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3, 6, 12 hours, 1, 2, 4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled. MAIN OUTCOME MEASURES： BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method. RESULTS： All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it gradually decreased. CONCLUSION： MMP-9 expression increases in rat brain tissue after focal cerebral ischemia/reperfusion injury, which correlates with increased permeability of the BBB.

Propofol protects against blood-spinal cord barrier disruption induced by ischemia/reperfusion injury

Propofol has been shown to exert neuroprotective effects on the injured spinal cord.However,the effect of propofol on the blood-spinal cord barrier（BSCB） after ischemia/reperfusion injury（IRI） is poorly understood.Therefore,we investigated whether propofol could maintain the integrity of the BSCB.Spinal cord IRI（SCIRI） was induced in rabbits by infrarenal aortic occlusion for 30 minutes.Propofol,30 mg/kg,was intravenously infused 10 minutes before aortic clamping as well as at the onset of reperfusion.Then,48 hours later,we performed histological and m RNA/protein analyses of the spinal cord.Propofol decreased histological damage to the spinal cord,attenuated the reduction in BSCB permeability,downregulated the m RNA and protein expression levels of matrix metalloprotease-9（MMP-9） and nuclear factor-κB（NF-κB）,and upregulated the protein expression levels of occludin and claudin-5.Our findings suggest that propofol helps maintain BSCB integrity after SCIRI by reducing MMP-9 expression,by inhibiting the NF-κB signaling pathway,and by maintaining expression of tight junction proteins.