Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, reverses cerebrovascular dysfunction and cognitive impairments in 18-mo-old diabetic animals.

Diabetes mellitus (DM) is a leading risk factor for age-related dementia, but the mechanisms involved are not well understood. We previously discovered that hyperglycemia induced impaired myogenic response (MR) and cerebral blood flow (CBF) autoregulation in 18-mo-old DM rats associated with blood-brain barrier (BBB) leakage, impaired neurovascular coupling, and cognitive impairment. In the present study, we examined whether reducing plasma glucose with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) luseogliflozin can ameliorate cerebral vascular and cognitive function in diabetic rats. Plasma glucose and HbA1c levels of 18-mo-old DM rats were reduced, and blood pressure was not altered after treatment with luseogliflozin. SGLT2i treatment restored the impaired MR of middle cerebral arteries (MCAs) and parenchymal arterioles and surface and deep cortical CBF autoregulation in DM rats. Luseogliflozin treatment also rescued neurovascular uncoupling, reduced BBB leakage and cognitive deficits in DM rats. However, SGLT2i did not have direct constrictive effects on vascular smooth muscle cells and MCAs isolated from normal rats, although it decreased reactive oxygen species production in cerebral vessels of DM rats. These results provide evidence that normalization of hyperglycemia with an SGLT2i can reverse cerebrovascular dysfunction and cognitive impairments in rats with long-standing hyperglycemia, possibly by ameliorating oxidative stress-caused vascular damage.NEW & NOTEWORTHY This study demonstrates that luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, improved CBF autoregulation in association with reduced vascular oxidative stress and AGEs production in the cerebrovasculature of 18-mo-old DM rats. SGLT2i also prevented BBB leakage, impaired functional hyperemia, neurodegeneration, and cognitive impairment seen in DM rats. Luseogliflozin did not have direct constrictive effects on VSMCs and MCAs isolated from normal rats. These results provide evidence that normalization of hyperglycemia with an SGLT2i can reverse cerebrovascular dysfunction and cognitive impairments in rats with long-standing hyperglycemia, possibly by ameliorating oxidative stress-caused vascular damage.

20-HETE-promoted cerebral blood flow autoregulation is associated with enhanced pericyte contractility.

We previously reported that deficiency in 20-HETE or CYP4A impaired the myogenic response and autoregulation of cerebral blood flow (CBF) in rats. The present study demonstrated that CYP4A was coexpressed with alpha-smooth muscle actin (α-SMA) in vascular smooth muscle cells (VSMCs) and most pericytes along parenchymal arteries (PAs) isolated from SD rats. Cell contractile capabilities of cerebral VSMCs and pericytes were reduced with a 20-HETE synthesis inhibitor, HET0016, but restored with 20-HETE analog WIT003. Similarly, intact myogenic responses of the middle cerebral artery and PA of SD rats decreased with HET0016 and were rescued by WIT003. The myogenic response of the PA was abolished in SS and was restored in SS.BN5 and SS.Cyp4a1 rats. HET0016 enhanced CBF and impaired its autoregulation in the surface and deep cortex of SD rats. These results demonstrate that 20-HETE has a direct effect on cerebral mural cell contractility that may play an essential role in controlling cerebral vascular function.

[Influence of cerebral hyperthermia on intracranial pressure and autoregulation of cerebral circulation in patients with acute brain injury]. / Vliyanie tserebral'noi gipertermii na vnutricherepnoe davlenie i autoregulyatsiyu mozgovogo krovotoka u patsientov s ostroi tserebral'noi patologiei.

Background. Hyperthermia is a common symptom in ICU patients with brain injury. OBJECTIVE: To study the effect of hyperthermia on intracranial pressure (ICP) and cerebral autoregulation (Prx). MATERIAL AND METHODS: There were 8 patients with acute brain injury, signs of brain edema and intracranial hypertension. Cerebral autoregulation was assessed by using of PRx. ICP, CPP, BP, PRx were measured before and during hyperthermia. We have analyzed 33 episodes of cerebral hyperthermia over 38.30 C. Statistica 10.0 (StatSoft) was used for statistical analysis. RESULTS: Only ICP was significantly increased by 6 [3; 11] mm Hg (p<0.01). In patients with initially normal ICP, hyperthermia resulted increase of ICP in 48% of cases (median 24 [22; 28] mm Hg). In patients with baseline intracranial hypertension, progression of hypertension was noted in 100% cases (median 31 [27; 32] mm Hg) (p<0.01). Hyperthermia resulted intracranial hypertension regardless brain autoregulation status. CONCLUSION: Cerebral hyperthermia in patients with initially normal ICP results intracranial hypertension in 48% of cases. In case of elevated ICP, further progression of intracranial hypertension occurs in 100% of cases. Cerebral hyperthermia is followed by ICP elevation in both intact and impaired cerebral autoregulation.

Sex differences in the structure and function of rat middle cerebral arteries.

Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause.NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).

Induced Dynamic Intracranial Pressure and Cerebrovascular Reactivity Assessment of Cerebrovascular Autoregulation After Traumatic Brain Injury with High Intracranial Pressure in Rats.

OBJECTIVE: In previous work we showed that high intracranial pressure (ICP) in the rat brain induces a transition from capillary (CAP) to pathological microvascular shunt (MVS) flow, resulting in brain hypoxia, edema, and blood-brain barrier (BBB) damage. This transition was correlated with a loss of cerebral blood flow (CBF) autoregulation undetected by static autoregulatory curves but identified by induced dynamic ICP (iPRx) and cerebrovascular (iCVRx) reactivity. We hypothesized that loss of CBF autoregulation as correlated with MVS flow would be identified by iPRx and iCVRx in traumatic brain injury (TBI) with elevated ICP. METHODS: TBI was induced by lateral fluid percussion (LFP) using a gas-driven device in rats. Using in vivo two-photon laser scanning microscopy, cortical microcirculation, tissue oxygenation (NADH autofluoresence), and BBB permeability (fluorescein dye extravasation) were measured before and for 4 h after TBI. Laser Doppler cortical flux, rectal and brain temperature, ICP and mean arterial pressure (MAP), blood gases, and electrolytes were monitored. Every 30 min, a transient 10 mmHg rise in MAP was induced by i.v. bolus of dopamine. iPRx = ΔICP/ΔMAP and iCVRx = ΔCBF/ΔMAP. RESULTS: We demonstrated that iPRx and iCVRx correctly identified more severe loss of CBF autoregulation correlated with a transition of blood flow to MVS after TBI with high ICP compared to TBI without an increase in ICP. CONCLUSIONS: In TBI with high ICP, high-velocity MVS flow is responsible for the loss of CBF autoregulation identified by iPRx and iCVRx.

Monitoring of cerebral blood flow autoregulation in adults undergoing sevoflurane anesthesia: a prospective cohort study of two age groups.

Autoregulation of blood flow is a key feature of the human cerebral vascular system to assure adequate oxygenation and metabolism of the brain under changing physiological conditions. The impact of advanced age and anesthesia on cerebral autoregulation remains unclear. The primary objective of this study was to determine the effect of sevoflurane anesthesia on cerebral autoregulation in two different age groups. This is a follow-up analysis of data acquired in a prospective observational cohort study. One hundred thirty-three patients aged 18-40 and ≥65 years scheduled for major noncardiac surgery under general anesthesia were included. Cerebral autoregulation indices, limits, and ranges were compared in young and elderly patient groups. Forty-nine patients (37 %) aged 18-40 years and 84 patients (63 %) aged ≥65 years were included in the study. Age-adjusted minimum alveolar concentrations of sevoflurane were 0.89 ± 0.07 in young and 0.99 ± 0.14 in older subjects (P < 0.001). Effective autoregulation was found in a blood pressure range of 13.8 ± 9.8 mmHg in young and 10.2 ± 8.6 mmHg in older patients (P = 0.079). The lower limit of autoregulation was 66 ± 12 mmHg and 73 ± 14 mmHg in young and older patients, respectively (P = 0.075). The association between sevoflurane concentrations and autoregulatory capacity was similar in both age groups. Our data suggests that the autoregulatory plateau is shortened in both young and older patients under sevoflurane anesthesia with approximately 1 MAC. Lower and upper limits of cerebral blood flow autoregulation, as well as the autoregulatory range, are not influenced by the age of anesthetized patients. Trial registration ClinicalTrials.gov (NCT00512200).

Stroke in Pregnancy and Preeclampsia: Effect of Low-Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats.

BACKGROUND: Experimental preeclampsia (ePE) has been shown to have worsened outcome from stroke. We investigated the effect of low-dose aspirin, known to prevent preeclampsia, on stroke hemodynamics and outcome, and the association between the vasoconstrictor and vasodilator cyclooxygenase products thromboxane A2 and prostacyclin. METHODS AND RESULTS: Middle cerebral artery occlusion was performed for 3 hours with 1 hour of reperfusion in normal pregnant rats on day 20 of gestation and compared with ePE treated with vehicle or low-dose aspirin (1.5 mg/kg per day). Multisite laser Doppler was used to measure changes in cerebral blood flow to the core middle cerebral artery and collateral vascular territories. After 30 minutes occlusion, phenylephrine was infused to increase blood pressure and assess cerebral blood flow autoregulation. Infarct and edema were measured using 2,3,5-triphenyltetrazolium chloride staining. Plasma levels of thromboxane A2, prostacyclin, and inflammatory markers in plasma and cyclooxygenase levels in cerebral arteries were measured. ePE had increased infarction compared with normal pregnant rats (P<0.05) that was reduced by aspirin (P<0.001). ePE also had intact cerebral blood flow autoregulation and reduced collateral perfusion during induced hypertension that was also prevented by aspirin. Aspirin increased prostacyclin in ePE (P<0.05) without reducing thromboxane B2, metabolite of thromboxane A2, or 8-isoprostane-prostaglandin-2α, a marker of lipid peroxidation. There were no differences in cyclooxygenase levels in cerebral arteries between groups. CONCLUSIONS: Low-dose aspirin in ePE reduced infarction that was associated with increased vasodilator prostacyclin and improved collateral perfusion during induced hypertension. The beneficial effect of aspirin on the brain and cerebral circulation is likely multifactorial and worth further study.

Blood pressure-cerebral oxygen coupling model: A new approach for stroke risk prediction.

Stroke is a major cause of death and disability worldwide, but predicting its risk remains challenging. This study aimed to evaluate the cerebral blood flow autoregulation function of subjects with different stroke risk levels and predict their stroke risk. The coupling strength between cerebral oxygen and blood pressure signals was calculated by wavelet analysis and dynamic Bayesian inference and used as a quantitative index of cerebral blood flow autoregulation. A stroke prediction model based on the extreme random tree was constructed using the coupling strength and other data as input features. The results showed that the coupling strength was significantly higher in the high-risk group than the other groups. Moreover, the prediction model achieved an average accuracy of 0.80 across the three groups. The coupling strength of cerebral oxygen and blood pressure can be used as an objective index to predict stroke risk, which has implications for stroke prevention and intervention.

Impaired cerebral autoregulation detected in early prevasospasm period is associated with unfavorable outcome after spontaneous subarachnoid hemorrhage: an observational prospective pilot study.

BACKGROUND: Subarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes. METHODS: The pilot observational study included 29 SAH patients whose CA status was estimated 2-3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2-3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device. RESULTS: Statistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039). CONCLUSIONS: A relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 - Retrospectively registered, https://www. CLINICALTRIALS: gov/study/NCT06028906 .

Specific effect of hypobaria on cerebrovascular hypercapnic responses in hypoxia.

It remains unknown whether hypobaria plays a role on cerebrovascular reactivity to CO2 (CVR). The present study evaluated the putative effect of hypobaria on CVR and its influence on cerebral oxygen delivery (cDO2 ) in five randomized conditions (i.e., normobaric normoxia, NN, altitude level of 440 m; hypobaric hypoxia, HH at altitude levels of 3,000 m and 5,500 m; normobaric hypoxia, NH, altitude simulation of 5,500 m; and hypobaric normoxia, HN). CVR was assessed in nine healthy participants (either students in aviation or pilots) during a hypercapnic test (i.e., 5% CO2 ). We obtained CVR by plotting middle cerebral artery velocity versus end-tidal CO2 pressure (PET CO2 ) using a sigmoid model. Hypobaria induced an increased slope in HH (0.66 ± 0.33) compared to NH (0.35 ± 0.19) with a trend in HN (0.46 ± 0.12) compared to NN (0.23 ± 0.12, p = .069). PET CO2 was decreased (22.3 ± 2.4 vs. 34.5 ± 2.8 mmHg and 19.9 ± 1.3 vs. 30.8 ± 2.2 mmHg, for HN vs. NN and HH vs. NH, respectively, p < .05) in hypobaric conditions when compared to normobaric conditions with comparable inspired oxygen pressure (141 ± 1 vs. 133 ± 3 mmHg and 74 ± 1 vs. 70 ± 2 mmHg, for NN vs. HN and NH vs. HH, respectively) During hypercapnia, cDO2 was decreased in 5,500 m HH (p = .046), but maintained in NH when compared to NN. To conclude, CVR seems more sensitive (i.e., slope increase) in hypobaric than in normobaric conditions. Moreover, hypobaria potentially affected vasodilation reserve (i.e., MCAv autoregulation) and brain oxygen delivery during hypercapnia. These results are relevant for populations (i.e., aviation pilots; high-altitude residents as miners; mountaineers) occasionally exposed to hypobaric normoxia.

The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats.

BACKGROUND: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. METHODS: Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. RESULTS: Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. CONCLUSIONS: These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia.

A Cross-Sectional Study on Cerebral Hemodynamics After Mild Traumatic Brain Injury in a Pediatric Population.

The microvasculature is prominently affected by traumatic brain injury (TBI), including mild TBI (concussion). Assessment of cerebral hemodynamics shows promise as biomarkers of TBI, and may help inform development of therapies aimed at promoting neurologic recovery. The objective of this study was to assess the evolution in cerebral hemodynamics observable with transcranial Doppler (TCD) ultrasound in subjects suffering from a concussion at different intervals during recovery. Pediatric subjects between the ages of 14 and 19 years clinically diagnosed with a concussion were observed at different points post-injury. Blood flow velocity in the middle cerebral artery was measured with TCD. After a baseline period, subjects participated in four breath holding challenges. Pulsatility index (PI), resistivity index (RI), the ratio of the first two pulse peaks (P2R), and the mean velocity (MV) were computed from the baseline section. The breath hold index (BHI) was computed from the challenge sections. TCD detected two phases of hemodynamic changes after concussion. Within the first 48 h, PI, RI, and P2R show a significant difference from the controls (U = -3.10; P < 0.01, U = -2.86; P < 0.01, and U = 2.62; P < 0.01, respectively). In addition, PI and P2R were not correlated (rp = -0.36; P = 0.23). After 48 h, differences in pulsatile features were no longer observable. However, BHI was significantly increased when grouped as 2-3, 4-5, and 6-7 days post-injury (U = 2.72; P < 0.01, U = 2.46; P = 0.014, and U = 2.38; P = 0.018, respectively). To our knowledge, this is the first longitudinal study of concussions using TCD. In addition, these results are the first to suggest the multiple hemodynamic changes after a concussion are observable with TCD and could ultimately lead to a better understanding of the underlying pathophysiology. In addition, the different hemodynamic responses to a concussion as compared to severe traumatic brain injuries highlight the need for specific diagnostic and therapeutic treatments of mild head injuries in adolescents.

[The dynamics of cerebral vascular reserve in sleep apnea patients during continuous positive airway pressure therapy]. / Dinamika tserebral'nogo gemodinamicheskogo rezerva u bol'nykh s obstruktivnym apnoé sna na fone terapii postoiannym povyshenym davleniem v dykhatel'nykh putiakh.

AIM: To explore the possibility of cerebral hemodynamic reserve (CHR) normalization in patients with obstructive sleep apnea syndrome (OSAS), aged over fifty, who received continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: The main group (20 patients, aged 50-65 years, with severe OSAS) and the control group (20 volunteers without snoring and OSAS matched for age and physical status) were studied. Diagnosis included cardio-respiratory monitoring of nocturnal sleep and ultrasound examination of cerebral blood flow with functional tests (breath holding and hyperventilation) and calculating the coefficient of vasomotor reactivity (CVMR) before the start of CPAP-therapy and after one month therapy. RESULTS: The significant CVMR decrease in vertebral (VA) and basilar arteries (BA) in patients with OSAS compared to the control group was identified: 38.9±8.5 and 55.7±11.3 for VA, 36.8±15.7 and 54.0±5.4 for BA. After one month CPAP-therapy, no significant coefficient gains was observed: 38.9±8.5 and 42.3±9.1 for VA, 36.8±15.7 and 37.2±7.7 for BA. CONCLUSION: The reduction of CVMR in patients older than 50 years with severe OSAS suggests the disturbance of CHR. The absence of its recovery within one month of CPAP-therapy may be indicative of the irreversible damage of the cerebral blood flow regulation mechanisms. Continued observations for a longer period are needed.

Cerebral Perfusion Pressure Targets Individualized to Pressure-Reactivity Index in Moderate to Severe Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI) frequently triggers a disruption of cerebral autoregulation. The cerebral perfusion pressure (CPP) at which autoregulation is optimal ("CPPopt") varies between individuals, and can be calculated based on fluctuations between arterial blood pressure and intracranial pressure. This review assesses the effect of individualizing CPP targets to pressure reactivity index (a measure of autoregulation) in patients with TBI. Cochrane Central Register of Controlled Trials, MEDLINE®, Embase, and Cumulative Index of Nursing and Allied Health Literature were searched in March 2015 for studies assessing the effect of targeting CPPopt in TBI. We included all studies that assessed the impact of targeting CPPopt on outcomes including mortality, neurological outcome, and physiological changes. Risk of bias was assessed using the RTI Item Bank and evidence quality was considered using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Eight cohort studies (based on six distinct data sets) assessing the association between CPPopt and mortality, Glasgow Outcome Scale and physiological measures in TBI were included. The quality of evidence was deemed very low based on the GRADE criteria. Although the data suggest an association between variation from CPPopt and poor clinical outcome at 6 months, the quality of evidence prevents firm conclusions, particularly regarding causality, from being drawn. Available data suggest that targeting CPPopt might represent a technique to improve outcomes following TBI, but currently there is insufficient high-quality data to support a recommendation for use in clinical practice. Further prospective, randomized controlled studies should be undertaken to clarify its role in the acute management of TBI.

The clinical application and value of transcranial doppler monitoring senile cerebral blood flow autoregulation in elderly / 中国综合临床

Objective To study the clinical application and value of transcranial Doppler (TCD) monitoring senile cerebral blood flow autoregulation in elderly.Methods Two hundred cases patients with elderly hypertension and 200 cases normal eldly from May 2011 to December 2014 in the Second People 's Hospital of Fengrun District of Tangshan were chosen as hypertension group and control group.Cerebral artery peak systolic velocity,supine with a vertical artery in the brain(MCA) cerebral blood flow difference (CBFV) and X-W wave duration, cerebrovascular hemodynamic parameters of two group were monitored by TCD method and compared.Results The peak values of left vertebral artery (LVA), right vertebral artery (RVA), the left coronary artery(LCS), and right vertebral artery(RCS) of hypertension group were significantly lower than those in the control group((38.01±12.42) cm/s vs (45.21±8.95) cm/s, (35.54±13.25) cm/s vs (43.52±7.06) cm/s, (66.12±9.52) m/s vs (76.54±8.19) cm/s, (71.24± 11.25) cm/s vs (77.98± 10.74) cm/s, (55.34 ±14.52) cm/s vs (61.24±12.58) cm/s,(48.12±15.24) cm/s vs (58.46±18.85) cm/s;t=4.6821, 5.6987,6.2589,4.3671,2.2854,4.9875;P＜ 0.01).The peak Vp, the difference between the horizontal and vertical position CBFV, X-W wave duration, the parameter of DR, Cp, C, Co, Zc, Wv of arterial blood vessels (left internal carotid artery (LICA), right internal carotid artery (RICA), left middle cerebral artery (LMCA), right middle cerebral artery(RMCA) ,left anterior cerebral artery(LACA), right anterior cerebral artery(RACA), left anterior cerebral artery (LOA), right middle cerebral artery (ROA)) of hypertension group were significantly higher than those of control group((96.38±18.85) cm/s vs (83.56±13.41) cm/s, (103.04±35.42) cm/s vs (85.62±29.63) cm/s, (99.85±23.54) cm/s vs (83.12±22.67) cm/s, (102.84± 16.42) cm/s vs (86.23 ±21.34) cm/s, (85.06± 15.36) cm/s vs (73.16± 10.35) cm/s, (85.64± 15.34) cm/s vs (70.52± 18.56) cm/s, (34.85±8.74) cm/s vs (28.56±7.85) cm/s, (35.12± 11.20) cm/s vs (30.05± 6.88) cm/s, (7.22 ± ±2.54) cm/s vs (2.78± 1.87) cm/s, (23.74±5.23) cm/s vs (20.85±4.35) cm/s, (378.35±35.12) Pa? s/cm vs (314.53±36.21) Pa? s/cm, (8.16± 0.62) P/kPa vs (7.25± 0.68) P/kPa, (0.41 ± 0.05) ml/kPa vs (0.33±0.06) ml/kPa, (1.15±0.16) mL/kPa vs (0.84±0.13) ml/kPa, (346.13±42.63) dyn? s/cm5 vs (241.68±50.21) dyn? s/cm5, (21.47± 3.85) V/(cml? s) vs (11.24 ± 3.67) V/(cml? s);t =5.8954, 4.2589,4.8792,6.3985,6.3874,6.9852,5.6387,4.6892,6.0387,4.8562, 11.475,8.041,12.422, 11.820, 12.854,20.412;P＜0.01).Conclusion The function of automatic adjustment shows obvious abnormal cerebral blood flow in patients with hypertension, andthe TCD technology can response of cerebral blood flow autoregulation,which has important clinical value for diagnosis and treatment of cerebral infarction, stroke and other cardiovascular and cerebrovascular diseases.

Fluoxetine and sertraline attenuate postischemic brain injury in mice.

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1alpha proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1alpha proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Continuous assessment of cerebral autoregulation in subarachnoid hemorrhage / 中国康复理论与实践

@#ObjectiveTo examined how autoregulation is affected by vasospasm after subarachnoid hemorrhage (SAH) by using transcranial Doppler. MethodsThe moving correlation coefficient between slow changes of arterial blood pressure and mean or systolic flow velocity (FV), termed Mx and Sx, respectively, was used to characterize cerebral autoregulation. Vasospasm was declared when the mean FV increased to more than 120 cm/s and the Lindegaard ratio was more than 3. This occurred in 15 of 32 SAH patients.On the basis of the bilateral transcranial Doppler recordings of the middle cerebral artery in vasospastic patients, Mx and Sx were calculated for baseline and vasospasm. ResultsMx increased during vasospasm (0.46±0.32) and was significantly higher (P=0.03) than at baseline (0.21±0.24) Sx was also increased (0.22±0.26 vs 0.05±0.21,P=0.03). Mx correlated with mean FV (P=0.577, P=0.006) and the Lindegaard ratio (r=0.672,P<0.01).Mx(P=0.006) and Sx (P=0.044) were higher on the vasospastic side compared with the contralateral side.ConclusionThe increased Mx and Sx during cerebral vasospasm demonstrate impaired cerebral autoregulation. Mx and Sx provide additional information on changes in autoregulation in SAH patients.

An automatic selections method for cerebral blood flow autoregulation signals from neonates

Interpretation and quantification of cerebral blood flow autoregulation can be carreid out from step responses to arterial blood pressure changes estimated with various identification methods. However estimates usually need to be visually inspected to rejected some that are not physiologically acceptable...