Cerebral Blood Flow In Hippocampus Research Articles

Comparing single- and multi-post labeling delays for the measurements of resting cerebral and hippocampal blood flow for cerebrovascular testing in midlife adults.

To assess the reliability and validity of measuring resting cerebral blood flow (CBF) and hippocampal CBF using a single-post-labeling delay (PLD) and a multi-PLD pseudo-continuous arterial spin labeling (pCASL) protocol for cerebrovascular reactivity (CVR) testing. 25 healthy, midlife adults (57 ± 4years old) were imaged in a Siemens Prisma 3T magnetic resonance imaging (MRI) scanner. Resting CBF and hippocampal CBF were assessed using two pCASL protocols, our modified single-PLD protocol (pCASL-MOD) to accommodate the needs for CVR testing and the multi-PLD Human Connectome Project (HCP) Lifespan protocol to serve as the reference control (pCASL-HCP). During pCASL-MOD, CVR was calculated as the change in CBF from rest to hypercapnia (+9mmHg increase in end-tidal partial pressure of carbon dioxide [PETCO2]) and then normalized for PETCO2. The reliability and validity in resting gray matter (GM) CBF, white matter (WM) CBF, and hippocampal CBF between pCASL-MOD and pCASL-HCP protocols were examined using correlation analyses, paired t-tests, and Bland Altman plots. The pCASL-MOD and pCASL-HCP protocols were significantly correlated for resting GM CBF [r = 0.72; F (1, 23) = 25.24, p < 0.0001], WM CBF [r = 0.57; F (1, 23) = 10.83, p = 0.003], and hippocampal CBF [r = 0.77; F (1, 23) = 32.65, p < 0.0001]. However, pCASL-MOD underestimated resting GM CBF (pCASL-MOD: 53.7 ± 11.1 v. pCASL-HCP: 69.1 ± 13.1mL/100g/min; p < 0.0001), WM CBF (pCASL-MOD: 32.4 ± 4.8 v. pCASL-HCP: 35.5 ± 6.9mL/100g/min; p = 0.01), and hippocampal CBF (pCASL-MOD: 50.5 ± 9.0 v. pCASL-HCP: 68.1 ± 12.5mL/100g/min; p < 0.0001). PETCO2 increased by 8.0 ± 0.7mmHg to induce CVR (GM CBF: 4.8% ± 2.6%; WM CBF 2.9% ± 2.5%; and hippocampal CBF: 3.4% ± 3.8%). Our single-PLD pCASL-MOD protocol reliably measured CBF and hippocampal CBF at rest given the significant correlation with the multi-PLD pCASL-HCP protocol. Despite the lower magnitude relative to pCASL-HCP, we recommend using our pCASL-MOD protocol for CVR testing in which an exact estimate of CBF is not required such as the assessment of relative change in CBF to hypercapnia.

Characterization of posterior circulation blood perfusion in patients with different degrees of basilar artery tortuosity.

The morphology of basilar artery (BA) may affect posterior circulation blood perfusion. We aimed to investigate whether different degrees of BA tortuosity could lead to the alterations of posterior circulation perfusion. We collected 138 subjects with different BA tortuosity scores, including 32 cases of score 0, 45 cases of score 1, 43 cases of score 2, and 18 cases of score 3. A higher score represented a higher degree of BA tortuosity. Ordered logistic regression analysis was performed to investigate the risk factors for BA tortuosity. We quantitatively measured the cerebral blood flow (CBF) in eight posterior circulation brain regions using arterial spin labeling. SPSS 25.0 was used for statistical analysis. The correlation between the CBF and BA tortuosity was corrected by the Bonferroni method. The significance level was set at 0.006 (0.05/8). Hypertension (HR: 2.39; 95%CI: 1.23-4.71; P = 0.01) and vertebral artery dominance (HR: 2.38; 95%CI: 1.10-4.67; P = 0.03) were risk factors for BA tortuosity. CBF in occipital gray matter (R = -0.383, P < 0.001), occipital white matter (R = -0.377, P < 0.001), temporal gray matter (R = -0.292, P = 0.001), temporal white matter (R = -0.297, P < 0.001), and cerebellum (R = -0.328, P < 0.001) were negatively correlated with BA tortuosity degree. No significant correlation was found between the BA tortuosity degree and CBF in hippocampus (R = -0.208, P = 0.014), thalamus (R = -0.001, P = 0.988) and brainstem (R = -0.204, P = 0.016). BA tortuosity could affect posterior circulation blood perfusion. CBF was negatively correlated with BA tortuosity degree. The morphology of BA may serve as a biomarker for posterior circulation and the severity of posterior circulation ischemia.

Aged HIV-1 Tg26 Transgenic Mice display Vascular Dysfunction with No Alterations in Neurocognitive Function or Cerebral Blood Flow

Although combination antiretroviral therapy (cART) has markedly reduced HIV mortality and increased life expectancy, people living with HIV (PLWH) develop premature cognitive and brain aging, classified as HIV-associated neurocognitive disorder (HAND). Vascular dysfunction and expression of HIV-derived proteins have independently been associated with cognitive impairment without causality being established. Thus, we investigated the role of HIV viral proteins in endothelial dysfunction and cognitive impairment in an aged mouse model of HIV. We used 18-month-old Tg26 mice and their wild-type littermate controls. Tg26 mice express 7 out of the 9 HIV viral proteins under the control of the long-term repeat promoter and have previously been shown to exhibit signs of cognitive impairment at eight months of age. Conduction of concentration-response curves to acetylcholine in mesenteric arteries using wire myography revealed impaired endothelium-dependent relaxation in Tg26 mice compared to WT mice. Measurements of brain perfusion with arterial spin labeling magnetic resonance imaging showed no differences in the whole brain and hippocampal cerebral blood flow. In addition, there were no changes in the hippocampus volume, which has been reported to be reduced with cognitive impairments. Two methods were employed to assess the cognitive abilities of the mice: Morris water maze (MWM) and the IntelliCage system. MWM requires human handling while the IntelliCage system is fully automated enabling the testing of mouse cognitive function during their active period and independently of human handling. Tg26 and WT mice underwent ten days of MWM testing and eight days of IntelliCage testing to assess spatial learning and memory. Tg26 mice showed no significant differences in latency to platform, distance swam to platform, or swim velocity when compared to their WT littermates. The IntelliCage results showed no differences in total visits, total visits with nose pokes, or total licks during the reversal learning period. Additionally, there were no significant differences in percent side error or place error indicating that cognitive function is not impaired in Tg26 mice. The Y-maze test further showed no differences in spontaneous alteration, a measure of spatial working memory. Altogether, our data shows that although 18-month-old female Tg26 mice develop endothelial dysfunction, they display no alterations in cerebral blood flow and no cognitive impairment indicating that systemic viral protein expression and vascular dysfunction might minimally contribute to neurocognitive impairment in HIV. R01HL130301 &amp; R01HL155265 (E.J.B). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute diazepam challenge normalises hippocampal cerebral blood flow in individuals at clinical high-risk for psychosis

Acute diazepam challenge normalises hippocampal cerebral blood flow in individuals at clinical high-risk for psychosis

An exploratory analysis of the relationship between cerebral flood flow, mood, and fluid cognition in older adults

AbstractBackgroundASL, a common MRI measure of cerebral blood flow (CBF), is thought to be a potential tool in the detection of preclinical Alzheimer’s disease. This exploratory analysis examined the relationship between CBF, mood, and fluid cognitive performance on the NIH Toolbox Cognition Battery (NIHTB‐CB) as part of an ongoing triglyceride intervention study.Method20 female older adults (age 65.6 ± 7.6) underwent ASL MRI when fasting and two hours after a triglyceride intervention. 3D pCASL MRI with background suppression was used to measure CBF in ml/100g/min using label duration = 1.8 s, post‐labeling delay = 2 s, labeling offset = 25‐30 mm, slices = 30, resolution = 2×2×4 mm3, SENSE‐factor = 2, TR/TE = 5000/18 ms. We also performed a reference scan (M0, 1 minute) identical to the one above but with no labeling or background suppression and TR = 10,000 ms. CBF was measured globally and in four regions of interest: angular gyrus (AG), posterior cingulate (PC), temporal lobe, and the hippocampus. Subjects completed the Generalized Anxiety Disorder Scale (GAD‐7) and MoCA at screening. The NIHTB‐CB was completed following the second MRI, and age‐adjusted scores were used in all analyses.ResultBaseline global CBF, AG CBF, and hippocampal CBF negatively correlated with GAD‐7 scores (r = ‐.797, p&lt;.0001; r = ‐.635, p = .0026; r = ‐.620, p = .0036, respectively). In contrast, global CBF and hippocampal CBF positively correlated with performance on the MoCA (r = .501, p = .0243; r = .546, p = .0126, respectively). Post‐intervention CBF in 3 of the 4 areas of interest positively correlated with fluid measures on the NIHTB‐CB, including the Flanker (AG: r = .528, p = .0166), Picture Sequence Memory Test (AG: r = .501, p = .0245; temporal lobe: r = .578, p = .0077), List Sorting Test (PC: r = .508, p = .0241), and fluid composite scores (AG: r = .610, p = .0043).ConclusionGreater anxiety correlated with lower baseline CBF overall and in the AG and hippocampus. Post‐lipid CBF correlated with better performance in working memory, executive function, and episodic memory. These results align with our predictions based on each of these regions’ functions. Further research exploring the relationship between mood and CBF is warranted, as well as investigating the effects of APOE4 status on these associations.

17 Education Moderates the Association Between Hippocampal CBF and Memory in Women but Not Men

Objective:Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.Participants and Methods:Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.Results:CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.Conclusions:These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.

Long period changes of hippocampal cerebral blood flow and its correlation with anxiety-like behavior and inflammation after incomplete cerebral ischemia reperfusion in rats.

This study was designed to summarize the changes of cerebral blood flow (CBF) in the bilateral hippocampal CA1 region of the hemorrhagic shock reperfusion (HSR) model of rats and their correlation with anxiety-like behavior and inflammation. Rats were randomly divided into the HSR group and the Sham group. 30 rats in each group were subdivided into 5 time points (1 w, 2 w, 4 w, 8 w, and 12 w) for examination. 3D-arterial spin labeling (3D-ASL) was performed. Long period anxiety-like behaviors were analyzed through the open field test. Histopathology was used to detect astrocytic activation in bilateral hippocampus. The concentrations of pro-inflammatory cytokines were analyzed by ELISA. At 1, 2, 4, and 8 weeks, CBF in bilateral hippocampus CA1 area of the rats in the Sham group was significantly higher than the rats in the HSR group. The rats in the HSR group had significantly shorter total traveled distance, lower velocity, and less rearing counts than those in the Sham group at 1, 2, 4, 8, and 12 weeks after the surgery. The CBF at 1, 2, 4, 8, and 12 weeks after the surgery had positive correlation with the total traveled distance, velocity, and rearing counts in the open field test. The rats in the HSR group had significantly higher GFAP intensity and the concentrations of IL-6, IL-1β, and TNF-α than those in the Sham group at 1, 2, 4, 8, and 12 weeks after the surgery. The CBF at 1, 2, 4, 8 and 12 weeks after the surgery had significantly negative correlation with the GFAP intensity and the concentrations of IL-6, IL-1β, and TNF-α. In conclusion, CBF in bilateral hippocampus CA1 area, spatial exploration ability in rats with HSR were decreased while the astrocyte activation was enhanced. During the long period after the induction of HSR, the value of CBF in bilateral hippocampus CA1 area was proved to have significant correlation with anxiety-like behaviors and astrocyte activation.

Alterations to Cerebral Perfusion, Metabolite Profiles, and Neuronal Morphology in the Hippocampus and Cortex of Male and Female Mice during Chronic Exposure to a High-Salt Diet.

Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging.

Cannabidiol in the treatment and prevention of Alzheimer’s disease – a comprehensive overview of in vitro and in vivo studies

Introduction and purpose. Dementia is a major public health problem. Alzheimer’s disease (AD) accounts for 60% of dementia cases. However, AD is currently considered as an incurable disorder and the only few drugs available for its treatment are mostly symptomatic. In the quest for novel drugs for this devastating disease, cannabidiol (CBD) has been recently gaining attention due to its multiple properties, such as an ability to interact with various receptors, anti-inflammatory and antioxidative effects and many more. The aim of this review article was to summarize findings on the effect of CBD on AD with a focus on molecular mechanisms of CBD’s action and therapeutic effects which it exerts.&#x0D; Description of the state of knowledge. In vitro studies, carried out on cell models of AD, showed anti-inflammatory and antioxidative properties of CBD through a suppression of pro-inflammatory genes and causing a reduction of production of, among others, nitric oxide. Moreover, CBD was proven to decrease amyloid β (Aβ) production, reduce formation and aggregation of tau fibrils, protect against microglial and Aβ-induced neurotoxicity and prevented the Aβ-induced deficit in long-term potentiation in hippocampus. In vivo studies, conducted mostly on mice models of AD, indicated that CBD improves memory and spatial learning, reverses deficit in social and object recognition, reduces anxiety-like behaviors and improves glucose metabolism. One study including humans demonstrated that CBD enhances cerebral blood flow in hippocampus. Currently there are two ongoing clinical trials on the use of CBD in AD-associated agitation.&#x0D; Conclusions. Both in vitro and in vivo studies indicate that cannabidiol appears promising in the treatment and prevention of Alzheimer’s disease.

Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer's Disease Biomarker-Positive Older Adults.

Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.

Association of central arterial stiffness with hippocampal blood flow and N-acetyl aspartate concentration in hypertensive adult Dahl salt sensitive rats.

Background:Central arterial stiffness (CAS) is associated with elevated arterial blood pressure (BP) and is likely associated with stiffening of cerebral artery walls, with attendant cerebral hypoperfusion, neuronal density loss and cognitive decline. Dahl salt-sensitive (Dahl-S) rats exhibit age-associated hypertension and memory loss, even on a normal salt intake.Method:We sought to explore whether central arterial pulse wave velocity (PWV), a marker of CAS, is associated with hippocampal cerebral blood flow (CBF) and neuronal density in hypertensive Dahl-S rats. We measured systolic BP (by tail-cuff plethysmography), aortic PWV (by echocardiography) and CBF and N-acetyl aspartate (NAA) (by magnetic resonance imaging) in 6 month-old male Dahl-S rats (n = 12).Results:Greater PWV was significantly associated with lower CBF and lower NAA concentration in the hippocampus, supporting a role of CAS in cerebrovascular dysfunction and decline in cognitive performance with aging.Conclusion:These findings implicate increased CAS in cerebral hypoperfusion and loss of neuronal density and function in the Dahl-S model of age-associated cardiovascular dysfunction.

Entorhinal Perfusion Predicts Future Memory Decline, Neurodegeneration, and White Matter Hyperintensity Progression in Older Adults.

Altered cerebral blood flow (CBF) has been linked to increased risk for Alzheimer's disease (AD). However, whether altered CBF contributes to AD risk by accelerating cognitive decline remains unclear. It also remains unclear whether reductions in CBF accelerate neurodegeneration and development of small vessel cerebrovascular disease. To examine associations between CBF and trajectories of memory performance, regional brain atrophy, and global white matter hyperintensity (WMH) volume. 147 Alzheimer's Disease Neuroimaging Initiative participants free of dementia underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) to measure CBF and serial neuropsychological and structural MRI examinations. Linear mixed effects models examined 5-year rate of change in memory and 4-year rate of change in regional brain atrophy and global WMH volumes as a function of baseline regional CBF. Entorhinal and hippocampal CBF were examined in separate models. Adjusting for demographic characteristics, pulse pressure, apolipoprotein E ɛ4 positivity, cerebrospinal fluid p-tau/Aβ ratio, and neuronal metabolism (i.e., fluorodeoxyglucose standardized uptake value ratio), lower baseline entorhinal CBF predicted faster rates of decline in memory as well as faster entorhinal thinning and WMH progression. Hippocampal CBF did not predict cognitive or brain structure trajectories. Findings highlight the importance of early cerebrovascular dysfunction in AD risk and suggest that entorhinal CBF as measured by noninvasive ASL MRI is a useful biomarker predictive of future cognitive decline and of risk of both.

APOE moderates the effect of hippocampal blood flow on memory pattern separation in clinically normal older adults.

Pattern separation, the ability to differentiate new information from previously experienced similar information, is highly sensitive to hippocampal structure and function and declines with age. Functional MRI studies have demonstrated hippocampal hyperactivation in older adults compared to young, with greater task-related activation associated with worse pattern separation performance. The current study was designed to determine whether pattern separation was sensitive to differences in task-free hippocampal cerebral blood flow (CBF) in 130 functionally intact older adults. Given prior evidence that apolipoprotein E e4 (APOE e4) status moderates the relationship between CBF and episodic memory, we predicted a stronger negative relationship between hippocampal CBF and pattern separation in APOE e4 carriers. An interaction between APOE group and right hippocampal CBF was present, such that greater right hippocampal CBF was related to better lure discrimination in noncarriers, whereas the effect reversed directionality in e4 carriers. These findings suggest that neurovascular changes in the medial temporal lobe may underlie memory deficits in cognitively normal older adults who are APOE e4 carriers.

Evaluation of cerebral blood flow in the hippocampus, thalamus, and basal ganglia and the volume of the hippocampus in dogs before and during treatment with prednisolone.

To examine whether glucocorticoid (GC) administration alters hippocampal cerebral blood flow (CBF) or volume in dogs. 6 clinically normal adult Beagles. Each dog underwent CT and MRI to measure the CBF in the hippocampus, basal ganglia, thalamus, and cerebral cortex and the volume of the hippocampus in each hemisphere of the brain before (day 0) and during (days 7 and 21) a 21-day treatment with prednisolone (1.0 mg/kg, PO, q 24 h) and famotidine (0.5 mg/kg, PO, q 12 h). Results for hippocampal volume, anesthesia-related variables, and semiquantitative measurements of CBF (hemisphere-specific ratios of the CBF in the hippocampus, basal ganglia, and thalamus relative to the CBF in the ipsilateral cerebral cortex and the left cerebral cortex CBF-to-right cerebral cortex CBF ratio) were compared across assessment time points (days 0, 7, and 21). The ratios of CBF in the right hippocampus and right thalamus to that in the right cerebral cortex on day 21 were significantly lower than those on day 0. No meaningful differences were detected in results for the hippocampal volume in either hemisphere or for the anesthesia-related variables across the 3 time points. Results indicated that GC administration reduced CBF in the hippocampus and thalamus in dogs of the present study, similar to that which occurs in humans. Research on GC-related brain alteration in dogs could potentially contribute to advancements in understanding Alzheimer disease in humans and neurodegenerative conditions in dogs.

Hippocampal cerebral blood flow increased following low-pressure hyperbaric oxygenation in firefighters with mild traumatic brain injury and emotional distress.

Recent evidence suggests that hyperbaric oxygenation (HBO), which has been used as an effective treatment for certain types of tissue injury, may change neural activities in the human brain and subsequently improve symptoms of psychiatric disorders. To scrutinize the neural mechanism of HBO in the human brain, we investigated whether 20 sessions of HBO changed regional cerebral blood flow (rCBF) of the limbic system in firefighters with mild traumatic brain injury (mTBI) and subjective emotional distress. Twenty firefighters with mTBI and mild emotional distress were treated with HBO at a relatively low pressure of 1.3 atmospheres absolute for 45 min a day for 20 consecutive days (the mild emotional distress group). The rCBF of the limbic system was measured using an arterial spin labeling perfusion magnetic resonance imaging before and after the HBO. Analyses were performed on the data from fourteen individuals who completed the study and 14 age- and sex-matched healthy firefighters (the comparison group). Firefighters in the mild emotional distress group showed increase rCBF following HBO in a cluster encompassing the right hippocampal and parahippocampal regions (peak t = 4.31; cluster size = 248 mm3)(post-hoc analysis, z = 5.92, p < 0.001) that had lower rCBF relative to the comparison group at baseline (post-hoc analysis, t = -2.20, p = 0.04). The current study demonstrated that low-pressure HBO might increase rCBF of the hippocampal and parahippocampal regions, suggesting a potential underpinning mechanism of HBO in the human brain.

Effects of Lisinopril on Arterial Stiffness, Cerebral Blood Flow, Neuronal Viability and Cortical Thickness in Late‐Life Hypertension in Dahl‐S Rats

Effects of Lisinopril on Arterial Stiffness, Cerebral Blood Flow, Neuronal Viability and Cortical Thickness in Late‐Life Hypertension in Dahl‐S Rats

Effects of Lisinopril on Arterial Stiffness, Cerebral Blood Flow and Cortical Thickness in Hypertensive Dahl‐S Rats

Study objectivesCentral arterial stiffness (CAS), associated with hypertension, is likely underlies the stiffening of cerebral arterial wall resulting in cerebral hypoperfusion, neuronal density loss and cognitive decline. We previously found associations between pulse wave velocity (PWV), a marker of CAS, and hippocampal cerebral blood flow (CBF) and neuronal density in 6‐mo old hypertensive Dahl salt‐sensitive (Dahl‐S) rats. This study examined the effect of ACE inhibitor, Lisinopril, on cardiovascular and brain parameters in hypertensive Dahl‐S rats.MethodsMale Dahl‐S rats (n=32) were fed with a normal salt diet (0.5% NaCl) for a duration of study. Systolic blood pressure (SBP), PWV (by echocardiography); hippocampal N‐acetyl aspartate (NAA) concentration, hippocampal CBF were measured at 6‐mo of age (baseline) and after 3‐mo and 6‐mo of Lisinopril (15mg/kg body weight/day in drinking water; n=14) or control (n=18) treatment. NAA was measured using proton spectroscopy in a 7T Bruker Biospec MRI scanner; CBF was measured using continuous arterial spin labeling (CASL) in the coronal slice with the largest hippocampal area; cortical thickness (CT) analysis was done using a T2 weighted RARE 3D image (n=12). Advanced Normalization Tools (ANTs) were used for the CT estimation. T‐test and 2‐way ANOVA linear mix effect model analyses were performed in R, EXCEL and MATLAB. Data presented as mean±SE.ResultsAt 6‐mo of age, the Dahl‐S rats developed advanced hypertension vs. 3‐mo (SBP: 164±4 vs. 141±3 mmHg; P&lt;0.01, t‐test). SBP of non‐treated (NT) animals was steadily high at all time points while treated animals exhibited a decrease in SBP at 9‐mo vs. 6‐mo of age. SBP remained low from 9‐mo to 12‐mo of age (Fig. 1a). In treated animals, PWV decreased at all timepoints after 6‐mo of age. For NT animals, PWV remained steady from 6‐mo to 9‐mo but increases from 9‐mo to12‐mo of age (Fig. 1b). Hippocampal CBF of NT animals decreased in a downwards trend but remain stabilized in the treated group across timepoints (Fig. 1c). Likewise, the hippocampal NAA, among treated animals remained stabilized, while in NT animals this parameter fluctuated with an eventual downwards trend (Fig. 1d). The mean difference maps of the CT for the NT and treated rats are similar except for the regions denoted by the red arrows when comparing treated to NT (Fig. 2a–b). The occipital region showed cortical thickening (blue) and parietal region showed cortical thinning (yellow). The P value maps show that those regions of significant thickening and thinning are greater in the treated vs. NT rats (Fig. 2c–d).ConclusionThe posterior cerebral artery is a dominant source of perfusion to the hippocampus and the occipital lobe; thus, our findings suggest a coherent pattern through which CAS can affect the cerebral arteries in hypertensive Dahl‐S rats. Lisinopril treatment decrease CAS and improve regional CBF and neuronal density. Therefore, CAS may be a therapeutic target for vascular dementia.Support or Funding InformationThe work was supported by the Intramural Research Program of the National Institute on Aging of the National Institutes of Health.Longitudinal changes in cardiovascular parameters in Lisinopril treated Dahl‐S rats. Systolic blood pressure SBP (a), pulse wave velocity PWV (b), hippocampal CBF (c), and NAA (d) in Lisinopril treated (T) and nontreated (NT) rats. By 2‐way ANOVA Linear Mixed Effects: *p &lt; 0.001 vs. age‐matched treated rats; #p &lt; 0.03 vs. 6‐mo, ## p &lt;0.001 vs. 6‐mo; by paired T‐test (c, d): * p = 0.07 vs. 6‐mo; # p = 0.06 vs. 9‐mo NT.Figure 1Mean Differences in Cortical Thickness and their p value maps (6‐mo subtracted by 12‐mo). Mean difference between age 6‐mo and 12‐mo of (a) nontreated animals and (b) lisinopril treated animals. Blue indicates regions of thickening. Yellow indicated regions of thinning. Occipital and parietal regions indicated by the red arrows. P value map of nontreated animals (c) and lisinopril treated animals (d). All insignificant p values &gt; 0.05 were revalued as 0.05 for visualization purposes.Figure 2

Impacts of hippocampal blood flow on changes in left ventricular wall thickness in patients with chronic heart failure

BackgroundAlthough depressive symptoms increased mortality and hospitalization in chronic heart failure (CHF) patients, the underlying mechanism remains unclear. The aim of this study was to investigate whether an alteration in hippocampal perfusion, which is the neural substrate of depressive symptoms, is associated with changes in cardiac structures and/or functions in CHF patients. MethodsWe used baseline data of 70 CHF patients (66.8 ± 8.9 yrs, 32.5% women), including cerebral blood flow (CBF) in the hippocampus, geriatric depression scale (GDS) scores and echocardiographic parameters, in the Brain Assessment and Investigation in Heart Failure Trial (B-HeFT) (UMIN000008584). Echocardiography was repeated at 3.1 ± 0.5 years after the baseline evaluation. We first tested voxel-wise regression model with hippocampal CBF as dependent variable and each of echocardiographic parameter change as independent variable, adjusted for age and sex. Structural equation modeling was used to test a mediation effect of cognitive test scores on associations between hippocampal perfusion and changes in cardiac structures and/or functions. ResultsBaseline anterior hippocampal CBF was negatively correlated with changes in left ventricular posterior wall thickness (PWT) (P < 0.05 with family-wise error corrections). An existence of depressive symptoms was positively correlated with the baseline anterior CBF and negatively with the PWT changes (P < 0.05, both). There were both direct effects of the baseline anterior hippocampal CBF on PWT thinning and effects mediated through the depressive symptoms (P < 0.05, both). ConclusionsThis study provides the first evidence that the alteration in hippocampal perfusion may lead to changes in cardiac structures via increase in depressive symptoms in CHF patients.

319 - Neurovascular coupling mediated by neuronal nitric oxide in hippocampus and the redox cycle of ascorbate and nitrite

Neurovascular coupling is critical for neuronal integrity and survival as it orchestrates the rapid and transient delivery of bioenergetic substrates by the local vasculature to neighboring cells, according to energy demands imposed by neural activation. Failure in neurovascular coupling, either during aging and disease (Alzheimer´s disease, AD) or following acute hypoxic conditions, compromises brain integrity and functionality. The regulation of neurovascular coupling is under the concerted cooperation of the cells comprising the neurovascular unit. However, the complementary task of identifying modulators of NO activity on neurovascular coupling has remained largely underappreciated. We have come to conjecture that the redox and functional interplay of nitric oxide with ascorbate and nitrite would modulate the functionality of glutamatergic synapses in terms of neurovascular coupling. By using a multimodal approach to probe the dynamics of NO, ascorbate and cerebral blood flow in vivo in hippocampus of Wistar and Fisher 344 rats and of a triple transgenic mice model of AD we support that (1) neuronal-derived NO acts as a direct mediator of neurovascular coupling, (2) upon glutamatergic stimulation, volume signaling by NO is an intrinsically controlled mechanism due to increased blood flow, (3) neurovascular coupling is impaired in AD and aging due to vascular dysfunction, (4) under acidic/hypoxic conditions, nitrite is reduced by ascorbate to NO and (5) the redox interaction of nitrite/ascorbate/NO contributes to neurovascular coupling. Given that nitrite increases NO bioavailability and augments cerebral blood flow in hippocampus one may envisage that dietary nitrate via the nitrate:nitrite:NO pathway may help sustaining neurovascular coupling in aging and disease.

Mechanisms of Antidepressant Response to Electroconvulsive Therapy Studied With Perfusion Magnetic Resonance Imaging

BackgroundConverging evidence suggests that electroconvulsive therapy (ECT) induces neuroplasticity in patients with severe depression, though how this relates to antidepressant response is less clear. Arterial spin-labeled functional magnetic resonance imaging tracks absolute changes in cerebral blood flow (CBF) linked with brain function and offers a potentially powerful tool when observing neurofunctional plasticity with functional magnetic resonance imaging. MethodsUsing arterial spin-labeled functional magnetic resonance imaging, we measured global and regional CBF associated with clinically prescribed ECT and therapeutic response in patients (n = 57, 30 female) before ECT, after two treatments, after completing an ECT treatment “index” (∼4 weeks), and after long-term follow-up (6 months). Age- and sex-matched control subjects were also scanned twice (n = 36, 19 female), ∼4 weeks apart. ResultsPatients with lower baseline global CBF were more likely to respond to ECT. Regional CBF increased in the right anterior hippocampus in all patients irrespective of clinical outcome, both after 2 treatments and after ECT index. However, hippocampal CBF increases postindex were more pronounced in nonresponders. ECT responders exhibited CBF increases in the dorsomedial thalamus and motor cortex near the vertex ECT electrode, as well as decreased CBF within lateral frontoparietal regions. ConclusionsECT induces functional neuroplasticity in the hippocampus, which could represent functional precursors of ECT-induced increases in hippocampal volume reported previously. However, excessive functional neuroplasticity within the hippocampus may not be conducive to positive clinical outcome. Instead, our results suggest that although hippocampal plasticity may contribute to antidepressant response in ECT, balanced plasticity in regions relevant to seizure physiology including thalamocortical networks may also play a critical role.