Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea level.The CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS groups.Statistical analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)curves.Results The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those without.Cortical CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753.Conclusion Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression

BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain brain regions,such as the cerebellum,highlighting a need for further research to support the current understanding of this disease.AIM To study brain changes in depressed adolescents.METHODS This study enrolled 34 adolescents with depression and 34 age-,sex-,and education-level-matched healthy control(HC)individuals.Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow(CBF)analysis,respectively.Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses.RESULTS The cerebellum,superior frontal gyrus,cingulate gyrus,pallidum,middle frontal gyrus,angular gyrus,thalamus,precentral gyrus,inferior temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals.These patients with depression further presented with a pronounced drop in CBF in the left pallidum(group=98,and peak t=-4.4324),together with increased CBF in the right percental gyrus(PerCG)(group=90,and peak t=4.5382).In addition,17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus(r=-0.5231,P<0.01).CONCLUSION The right PerCG showed structural and CBF changes,indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging

BACKGROUND Global and regional cerebral blood flow(CBF)changes in patients with unilateral internal carotid artery occlusion(ICAO)are unclear when the dual post-labeling delays(PLD)arterial spin labeling(ASL)magnetic resonance imaging(MRI)technique is used.Manual delineation of regions of interest for CBF measurement is time-consuming and laborious.AIM To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique.METHODS Twenty hospitalized patients with ICAO and sex-and age-matched controls were included in the study.Regional CBF was measured by Dr.Brain's ASL software.The present study evaluated differences in global,middle cerebral artery(MCA)territory,anterior cerebral artery territory,and Alberta Stroke Program Early Computed Tomography Score(ASPECTS)regions(including the caudate nucleus,lentiform nucleus,insula ribbon,internal capsule,and M1-M6)and brain lobes(including frontal,parietal,temporal,and insular lobes)between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s.RESULTS When comparing CBF between ICAO patients and controls,the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s;the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s,and it was lower in 9 brain regions at PLD 2.5 s;the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s.The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s.The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions,whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions.The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s,and in M6 at PLD 2.5 s.CONCLUSION Unilateral ICAO results in hypoperfusion in the global and MCA territories,especially in the ASPECTS area.Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

Optimal velocity encoding during measurement of cerebral blood flow volume using phase-contrast magnetic resonance angiography

This study investigated the effect of velocity encoding on measurement of brain blood flow and blood volume of inflow and outflow using phase-contrast magnetic resonance angiography. A single two-dimensional phase-contrast magnetic resonance angiography slice was applied perpendicular to the internal carotid artery and the vertebral artery at C2 level. For each subject, the velocity encoding was set from 30 to 90 cm/s with an interval of 10 cm/s for a total of seven settings. Various velocity encodings greatly affected blood flow volume, maximal blood flow velocity and mean blood flow velocity in the internal carotid artery, but did not significantly affect vertebral arteries and jugular veins. When velocity encoding was 60-80 cm/s, the inflow blood volume was 655 _＋ 118 mL/min, and the outflow volume was 506 _＋ 186 mL/min. The ratio of outflow/inflow was steady at 0.78-0.83, and there was no aliasing in any of the images. These findings suggest that velocity encodings of 60 80 cm/s should be selected during measurement of cerebral blood flow volume using phase-contrast magnetic resonance angiography.

The effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury

Objective To explore effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury. Methods 71 cases were divided into three groups according age: group A( 【 30 years) ,group B ( 30 ～ 50 years) 。

Hyperbaric oxygen therapy for cerebral blood flow and electroencephalogram in patients with acute cerebral infarction Choice for therapeutic occasion

BACKGROUND： Hyperbaric oxygen （HBO） therapy increases blood oxygen content, changes cerebral blood flow （CBF） and cerebral metabolism. Its therapeutic effects on cerebrovascular disease have been fully confirmed, but the occasion for HBO therapy is still unclear. OBJECTIVE： To observe the therapeutic effects of HBO therapy at different time on CBF and electroencephalogram （EEG） in patients with acute cerebral infarction （CI）. DESIGN： Randomized controlled trial. SETTING： Department of Neurology, Shidong Hospital, Yangpu District of Shanghai. PARTICIPANTS： Ninety-six inpatients with acute CI, admitted to Department of Neurology, Shidong Hospital, Yangpu District of Shanghai from January 2001 to December 2006, were involved in this experiment. The involved participants met the diagnosis criteria of acute CI and confirmed by skull CT or MRI. They all were patients with moderate CI （16- 30 points） according to neurologic deficit score formulated by Chinese Medical Association. Informed consents of detected items and therapeutic regimen were obtained from all the involved participants. They were randomized into two groups with 48 in each： early-stage treatment group and advanced-stage treatment group. Among the 48 patients in the early-stage treatment group, 21 male and 27 female, aged 53 -68 years, 22 patients were found with basal ganglia infarction, 10 with brain lobe infarction, 16 with multiple infarction, 27 accompanied with hypertension and 2 accompanied with diabetes meUitus. Among the 48 patients in the advanced-stage treatment group, 23 male and 25 female, aged 52 - 71 years, 25 patients were found with basal ganglia infarction, 10 with brain lobe infarction, 12 with multiple infarction, 1 with brain stem infarction, 28 accompanied with hypertension and 1 accompanied with diabetes mellitus. METHODS： After admission, patients of two groups received routine drug treatment. ① Patients in the early-stage treatment group and advanced-stage treatment group began to receive HBO therapy within one week of CI and 4 weeks after CI, respectively. The total course of treatment both was 2 weeks. EEG examination was carried out before and after therapy, and CBF was determined with ^133Xe inhalation.② Assessment criteria of curative effects： Basically cured： neurologic symptoms and body signs disappeared, could work and do housework; Markedly effective： score of neurologic deficit was decreased by over 21 points, could manage himself/herself partially; Effective： score of neurologic deficit was decreased by 8 to 12 points; Non-effective： Score was increased or decreased less than 8 points, neurologic deficit was worsened, even died. Total effective rate = （number of cured＋number of markedly effective＋number of effective）/ number of total cases ×100%. ③ t test and Chi-square test were used for comparing the difference of measurement data and enumeration data respectively, and Ridit analysis was used for comparing the difference of clinical curative effects. MAIN OUTCOME MEASURES： ① Comparison of EEG and CBF of patients from two groups before and after treatment. ②Comparison of post-treatment neurologic deficit of patients between two groups. RESULTS： All the involved 96 patients with CI participated in the final analysis. ① Clinical symptoms of patients from two groups after therapy were significantly improved as compared with those before therapy, and curative effects of early treatment group were better than those of advanced treatment group （ U = 1.99, P 〈 0.05 ） . ②After treatment, CBF in each region of brains, except for that in parietal lobe of patients in the advanced-stage treatment group, was significantly improved （P 〈 0.05 - 0.01）; The improvement of CBF of patients in the early-stage treatment group was more obvious than that in the early-stage treatment group （P 〈 0.05 - 0.01）. ③ The abnormal rate of EEF of patients from early-stage treatment group and advanced-stage treatment group before treatment was 94% and 96%, respectively. After treatment, improvement rate of EEG of patients in the early-stage treatment groulp was 95%, which was significantly different from that in the advanced-stage treatment group （82%, x^2=4.32, P 〈 0.05 ） CONCLUSION： HBO therapy both at early and advanced stages of CI （within 1 week and 4 weeks after CI attack） can improve CBF and EEG of patients with early CI, especially.

Pulsed arterial spin labeling effectively and dynamically observes changes in cerebral blood flow after mild traumatic brain injury

Cerebral blood flow is strongly associated with brain function, and is the main symptom and diagnostic basis for a variety of encephalopathies. However, changes in cerebral blood flow after mild traumatic brain injury remain poorly understood. This study sought to observe changes in cerebral blood flow in different regions after mild traumatic brain injury using pulsed arterial spin labeling. Our results demonstrate maximal cerebral blood flow in gray matter and minimal in the white matter of patients with mild traumatic brain injury. At the acute and subacute stages, cerebral blood flow was reduced in the occipital lobe, parietal lobe, central region, subcutaneous region, and frontal lobe. Cerebral blood flow was restored at the chronic stage. At the acute, subacute, and chronic stages, changes in cerebral blood flow were not apparent in the insula. Cerebral blood flow in the temporal lobe and limbic lobe diminished at the acute and subacute stages, but was restored at the chronic stage. These findings suggest that pulsed arterial spin labeling can precisely measure cerebral blood flow in various brain regions, and may play a reference role in evaluating a patient＇s condition and judging prognosis after traumatic brain injury.

Measurements Of Cerebral Blood Flow in Postasphyxiated Newborns by Color Doppler Imaging（CDI）

Cerebral blood flow of 10 asphyxiated term newborns was continuously measured during the first 7 days of life and compared with that of 10 normal term infants by CDI. Frequency spectrum and blood flow variables in the anterior, middle and posterior cerebral arteries were studied. The results showed evidently lower systolic amplitude in patients than that in normal subjects. End diastolic amplitude was zero in part of vessels, and values of bloed flow variables were all lower in day 1 of the life as compared with the control groups. Frequency spectrum recovered to normal patterns in 9 survived infants in day 2. but blood flow variables recovered to normal by day 7. Values of resistance index (RI) rose to 1 in some vessels of moderate hypoxic ischemic encephalopathy (HIE) infants and stayed at 1 in the severe HIE infants. It is concluded that low CBF plays a key role in brain damage of post-asphyxiated newborns and RI may be an important parameter in the evaluation prognosis.

A New Method for Evaluating Regional Cerebral Blood Flow Changes:Laser Speckle Contrast Imaging in a C57BL/6J Mouse Model of Photothrombotic Ischemia

The present study aimed to improve the processing of data acquired from laser speckle contrast imaging（LSCI） to provide a standardization method to explore changes in regional cerebral blood flow（r CBF） and to determine the correlations among r CBF, cerebral ischemic lesion volume and microvascular density over time in a focal ischemic region. C57BL/6J mice were subjected to focal photothrombotic（PT） ischemia. r CBF was measured using LSCI at different time points before and after PT ischemia through an intact skull. Standardized r CBF（Sr CBF）, defined as the ratio of r CBF measured in the ipsilateral region of interest（ROI） to that in the corresponding contralateral region, was calculated to evaluate potential changes. In addition, the volume of the ischemic lesion and the microvascular density were determined using Nissl staining and immunofluorescence, respectively. The relationships among the ischemic lesion volume, microvascular density and Sr CBF were analyzed over time. The results showed that the cortical r CBF measured using LSCI following PT ischemia in the C57BL/6J mice gradually increased. Changes in the cerebral ischemic lesion volume were negatively correlated with Sr CBF in the ischemic region. Changes in the microvascular density were similar to those observed in Sr CBF. Our findings indicate that LSCI is a practical technique for observing changes in murine cortical r CBF without skull opening and for analyzing the relationships among the ischemic lesion volume, microvascular density and Sr CBF following focal cerebral ischemia. Preliminary results also suggest that the use of LSCI to observe the formation of collateral circulation is feasible.

Electroacupuncture induces acute changes in cerebral cortical mi RNA profile, improves cerebral blood flow and alleviates neurological deficits in a rat model of stroke

Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters mi RNA expression in the cortex. In this study, we examined changes in the cerebral cortical mi RNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong（GV26） and Neiguan（PC6）, with a frequency of 2 Hz, continuous wave, current intensity of 3.0 m A, and stimulation time of 1 minute. Electroacupuncture increased cerebral blood flow and alleviated neurological impairment in the rats. mi RNA microarray profiling revealed that the vascular endothelial growth factor signaling pathway, which links cell proliferation with stroke, was most significantly affected by electroacupuncture. Electroacupuncture induced changes in expression of rno-mi R-206-3p, rno-mi R-3473, rno-mi R-6216 and rno-mi R-494-3p, and these changes were confirmed by quantitative real-time polymerase chain reaction. Our findings suggest that changes in cell proliferation-associated mi RNA expression induced by electroacupuncture might be associated with the improved cerebral blood supply and functional recovery following stroke.

REAL-TIME MONITORING OF MITOCHONDRIAL FUNCTION AND CEREBRAL BLOOD FLOW FOLLOWING FOCAL ISCHEMIA IN RATS

Focal ischemia due to reduction of cerebral blood flow(CBF),creates 2 zones of damage:the core area,which suffers severe damage,and penumbra area,which surrounds the core and suffers intermediate levels of injury.Objectives:A novel method is introduced,which evaluates mitochondrial function in the core and in the penumbra,during focal cerebral ischemia.Methods:Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion(MCAO)for 60 minutes,followed by 60 minutes of reperfusion.Mitochondrial function was assessed by a unique Multi-Site—Multi-Parametric(MSMP)monitoring system,which measures mitochondrial NADH using fluorometric technique,and CBF using Laser Doppler Flowmetry(LDF).Results:At the onset of occlusion,CBF dropped and NADH increased significantly only in the right hemisphere.CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra.After reperfusion,CBF and NADH recovered correspondingly to the intensity of ischemia.Conclusion:Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions,with an emphasis on mitochondrial function.

Improvement of regional cerebral blood flow after oral intake of ranched-chain amino acids in patients with cirrhosis

AIM： To evaluate the effect of oral intake of branchedchain amino acids （BCAA） on brain perfusion in patients with liver cirrhosis. METHODS： Single photon emission computed tomography scans were performed in 43 patients with cirrhosis and in 15 age-matched healthy subjects. Twenty-nine out of forty-three patients were randomly treated with either BCAA granules or placebo, and single photon emission computed tomography was performed before and after the treatment. We measured the regional cerebral blood flow values using a threedimensional stereotaxic region of interest template. RESULTS： Cirrhotic patients had regions of significant hypoperfusion in the bilateral central （right P = 0.039, P〈0.05; left P = 0.006 P〈0.01）, parietal （right P = 0.028, P〈0.05; left P = 0.009, P〈0.01）, angular （right P = 0.039, P〈0.05; left P = 0.008, P〈0.01）, and left pericallosal segments （P = 0.038 P〈0.05） as compared with healthy subjects. A significant increase in cerebral perfusion was observed 70 min after the oral intake of BCAA in the angular （right P = 0.012, P〈0.05; left P = 0.049, P〈0.05）, temporal （right P = 0.012, P〈0.05; left P=0.038, P〈0.05）, pericallosal segments （right P = 0.025, P〈0.05; left P = 0.049, P〈0.05） and left precentral （P = 0.044, P〈0.05）, parietal （P = 0.040, P〈0.05） and thalamus （P = 0.033, P〈0.05）. No significant change in perfusion was observed in the placebo group. CONCLUSION： Administration of BCAA rapidly improves cerebral perfusion.

Effect of the Principle of Activating Blood Circulation to Break Stasis on GMP-140 and D_2 Dimer in Patients with Acute Cerebral Infarction

Objective: To explore the clinical efficacy of the principle of activating blood circulation to break stasis (ABCBS) and its influence on platelet membranous protein particle (GMP-140) and D 2 dimer (D-dimer) before and after treatment. Methods: Eighty-eight patients with blood stasis syndrome (BSS) of acute cerebral infarction (ACI) were randomly divided into two groups, both of which were treated with conventional treatment, i.e. with western medicine (WM), with Salvia injection added through intravenously dripping.One of the two groups was used as the control and the other group as the treated group who had ABCBS herbs orally taken in addition. The duration of treatment course for both groups was 3 weeks. Results: There were changes in both groups over clinical symptoms, nerve function deficit scoring and GMP-140, D-dimer, but the treated group showed significantly better than that of the control group, ( P <0.05). Conclusion: ABCBS principle could serve as an important auxiliary treating method for BSS of ACI, as it can effectively alter the blood of ACI patients which was viscous, condense, coagulant and aggregating.

CLINICAL OBSERVATION ABOUT THE EFFECT OF BLOOD-LETTING OF JING-POINTS ON CEREBRAL BLOOD FLOW IN STROKE PATIENTS AT THE EARLY STAGE AND EXPERIMENTAL STUDY ON ITS MECHANISMS IN THE RABBIT

In this paper, the authors sum their research results about the effect of blood-letting of Jing (Well)-point on cerebral blood flow both in stroke patients and in experimental cerebral ischemia, cerebral hematoma and hypertension rabbits. In 30 cases of stroke (cerebral hemorrhage and cerebral infarction) patients, blood flow state of the anterior cerebral artery (ACA), middle cerebral artery (MCA) and the posterior cerebral artery (PCA), and the blood flow velocity of the bilateral vertebral artery (VA) and the basil artery (BA) are determined before and after pricking blood of the Twelve Jing-points. In experimental cerebral ischemia (by occlusion of the common carotid artery) rabbits, cerebral hematoma model rabbits and intravenous injection of noradrenaline induced hypertension rabbits, rheoencephalogram (REC) is detected before and after blood letting of the twelve "Jing"-points. In these 30 stroke patients, ultrasound Doppler examination’s results show that in 22 cases (73.33%) whose blood flow velocity decreases, after blood-letting of the 12 Jing-points, it increases significantly (P<0.01); in the rest 8 cases ( 26.67%) whose blood flow velocity speeds up, after treatment, it decreases evidently (P<0.01), showing a good dual-directional regulative effect of blood-letting therapy. In experimental cerebral ischemia rabbits, cerebral hematoma rabbits and hypertension rabbits whose REG lowers in the amplitude apparently (P<0.01), after blood letting stimulation of the 12 Jing-points, it increases at different degrees. Three patterns of stimulation as blood letting stimulation, pain stimulation and Jing-point stimulation, also the 3 factors of blood-letting therapy, may contribute to their effect on improvement of the cerebral blood flow. Somatic afferent nerve, sympathetic nerve of the vascular wall, central cholinergic nerve (M receptors) and adrenergic nerve (α receptors) participate in the effect of blood letting on cerebral blood flow.

Characteristics of traumatic brain injury models:from macroscopic blood flow changes to microscopic mitochondrial changes

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model.A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of>2 mm is used to induce severe brain injury.However,the different effects and underlying mechanisms of these two model types have not been proven.This study investigated the changes in cerebral blood flow,differences in the degree of cortical damage,and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3,4,and 5 m/s.We also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute(7 days)and chronic phases(30 days).The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased,and swelling and bulging of brain tissue,increased vascular permeability,and large-scale exudation occurred.In the 2 mm group,the main pathological changes were decreased cerebral blood flow,brain tissue loss,and cerebral vasospasm occlusion in the injured area.Substantial motor and cognitive impairments were found on day 7 after injury in the 2 mm group;at 30 days after injury,the motor function of the 2 mm group mice recovered significantly while cognitive impairment persisted.Transcriptome sequencing showed that compared with the 1 mm group,the 2 mm group expressed more ferroptosis-related genes.Morphological changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7,the mitochondria in both groups shrank and the vacuoles became larger;on day 30,the mitochondria in the 1 mm group became larger,and the vacuoles in the 2 mm group remained enlarged.By analyzing the proportion of mitochondrial subgroups in different groups,we found that the model mice had different patterns of mitochondrial composition at different time periods,suggesting that the difference in the degree of damage among traumatic brain injury groups may reflect the mitochondrial changes.Taken together,differences in mitochondrial morphology and function between the 1 and 2 mm groups provide a new direction for the accurate classification of traumatic brain injury.Our results provide reliable data support and evaluation methods for promoting the establishment of standard mouse controlled cortical impingement model guidelines.

Correlation between special brain area and blood perfusion in patients with cerebral infarction at convalescent period Feasibility for quantitative determination and estimation of learning and memory function

BACKGROUND： Presently, clinic memory scale is used to evaluate learning memory ability in most studies, and the influence of difference in measurement condition of individuals exists. OBJECTIVE： To study the correlation between regional cerebral blood flow （rCBF） perfusion and learning memory function in special brain regions of patients with cerebral infarction at convalescent period, and to try to find out a method which can quantitatively evaluate learning ability. DESIGN： Case observation, and correlation analysis. SETTINGS： Shandong Institute for Behavioral Medicine; the Affiliated Hospital of Jining Medical College. PARTICIPANTS： Totally 70 patients with cerebral infarction admitted to Department of Neurology, Jining Medical College between January 2004 and December 2005 were involved. The involved patients, 58 male and 12 female, were averaged （52±3） years, and they were all right handed. They all met the diagnosis criteria instituted by the Fourth National Conference on Cerebrovascular Disease, and were confirmed as cerebral infarction by skull CT or MRI. Informed consents of detected items were obtained from all the patients and relatives. METHODS： When the patients were at convalescent period, their learning and memory ability were measured with “ clinic memory scale （set A）”. The 18 patients whose total mark over 100 were regarded as good learning memory function group; The 23 cases whose total mark less than 70 were regarded as poor learning memory function group. RCBF of hippocampus, nucleus amygdalae, temporal cortex and prefrontal lobe of patients between two groups were measured and compared by single photon emission computed tomography （SPECT）. The total scores of the 18 good learning memory patients and 23 poor learning memory patients were taken as dependent variable Y, and their rCBFs of hippocampus, nucleus amygdale, temporal cortex and prefrontal lobe respectively as independent variable X for linear correlation analysis. MAIN OUTCOME MEASURES： Correlation of rCBF in different brain regions and learning memory ability in patients with cerebral infarction. RESULTS： ①The rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex of good learning memory function group were significantly higher than those of poor learning memory function group （P 〈 0.05）. ②In the good learning memory function group, rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex were significantly positively correlated with memory scale scores （ r = 0.961, 0.926, 0.954, 0.907, P 〈 0.05 ） , and also in the poor learning memory function group （r = 0.979, 0.976, 0.991, 0.953, P 〈 0.05 ） . CONCLUSION： The rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex of patients with cerebral infarction are significantly positively correlated with memory scale scores. Predicting learning memory ability of patients by quantitative determination of rCBF provides a quantitative and objective method for evaluating learning memory ability.

Characterization of cerebral blood flow dynamics with multiscale entropy

Based on the laser speckle contrast imaging(LSCI)and the multiscale entropy(MSE),we study in this work the blood flow dynamics at the levels of cerebral veins and the surrounding network of microcerebral vessels.We discuss how the phenylephrine-related acute peripheral bypertension is refected in the cerebral circulation and show that the observed changes are scale dependent,and they are signifcantly more pronounced in microcerebral vessels,while the macrocerebral dynamics does not demonstrate authentic inter-group distinctions.We also consider the permeability of blood-brain barrier(BBB)and study its opening caused by sound exposure.We show that alterations associated with the BBB opening can be revealed by the analysis of blood flow at the level of macrocerebral vessels.

Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits.There are important differences in the factors,clinical events and outcomes associated with the stroke in infants and adults.However,mechanisms underlying age differences in the stroke development remain largely unknown.Therefore,treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children.The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke.Here,we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats.Using histological methods and magnetic resonance imaging,we found age differences in the type of intracranial hemorrhages.Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum.Using Doppler optical coherent tomography,we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs.adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs.adult brain in rats.However,adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier(BBB)permeability.The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB(occludin and claudin-5)in neonatal vs.mature brain in rats.