Cerebral Blood Flow Levels Research Articles

Direct angiotensin II type 2 receptor stimulation by compound 21 prevents vascular dementia

Angiotensin II type 2 (AT2) receptor activation has been reported to play a role in cognitive function, although its detailed mechanisms and pathologic significance are not fully understood. We examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) could prevent cognitive decline associated with hypoperfusion in the brain.We employed a bilateral common carotid artery stenosis (BCAS) model in mice as a model of vascular dementia. The Morris water maze task was performed 6 weeks after BCAS operation. Azilsartan (0.1 mg/kg/day) or C21 (10 μg/kg/day) was administered from 1 week before BCAS. Cerebral blood flow (CBF) and inflammatory cytokine levels were also determined. Wild–type (WT) mice showed significant prolongation of escape latency after BCAS, and this cognitive impairment was attenuated by pretreatment with azilsartan. Cognitive impairment was more marked in AT2 receptor knockout (AT2KO) mice, and the preventive effect of azilsartan on cognitive decline was weaker in AT2KO mice than in WT mice, suggesting that the improvement of cognitive decline by azilsartan may involve stimulation of the AT2 receptor. The significant impairment of spatial learning after BCAS in WT mice was attenuated by C21 treatment. The decrease in CBF in the BCAS–treated group was blunted by C21 treatment, and the increase in TNF–α and MCP–1 mRNA expression after BCAS was attenuated by C21 treatment. These findings indicate that direct AT2 receptor stimulation attenuates ischemic vascular dementia induced by hypoperfusion at least in part through an increase in CBF, and a reduction of inflammation.

Sensitivity and specificity of the cerebral blood flow reactions to acupuncture in the newborn infants presenting with hypoxic ischemic encephalopathy

To evaluate the effects of acupuncture integrated into the standard therapy, the condition of cerebral blood flow, and other syndromes associated with cerebral ischemia in the newborn infants. MATERIAL AND METHODS. A total of 131 pairs of puerperae and newborns with hypoxic ischemic encephalopathy were divided into four treatment groups. 34 children of the first group were given standard therapy (control), in the second group comprised of 33 mothers and children the standard treatment was supplemented by acupuncture, the third group included only 32 mothers given the acupuncture treatment alone, and the fourth group contained only 32 newborn infants treated by acupuncture. Each course of acupuncture treatment consisted of five sessions. Sensitivity and specificity of cerebral blood flow reactions were determined based on the results of the ROC-analysis and the area under the curve before and after the treatment. The treatment with the use of acupuncture greatly improved the cerebrospinal hemodynamics (p < 0.05). Other symptoms, viz. sleep disorders, vegetative reactivity and excitability were significantly reduced. The ROC analysis confirmed the effectiveness of acupuncture as a tool for the treatment of the impaired cerebral blood flow in the newborn babies. The high level of sensitivity (84.4-94.8%) associated with good specificity makes it possible to distinguish between the true positive and true negative cases. Acupuncture integrated into the treatment of "mother-baby" pairs presenting with hypoxic ischemic encephalopathy can be used to improve the initially low level of cerebral blood flow in neonates presenting with this condition.

Binswanger disease may benefit from omental arteries.

Binswanger disease may benefit from omental arteries.

Neuroprotective effects of the ergoline derivative nicergoline following transient and permanent focal cerebral ischemia in rats

Nicergoline has been widely used for various conditions, including cerebrovascular disorders and senile mental impairment. However, the precise mechanisms underlying this neuroprotection remain unknown. We investigated the neuroprotective properties of nicergoline on outcome after focal ischemia in rats. Sprague–Dawley rats were treated with nicergoline or vehicle through a gavage feeding needle for 7 days before the induction of ischemia. For ischemia, rats were subjected to transient middle cerebral artery occlusion (tMCAO) or permanent middle cerebral artery occlusion (pMCAO). Magnetic resonance imaging was used to obtain cerebral blood flow (CBF) measurements at 24 hours after tMCAO and pMCAO. Nicergoline significantly diminished infarct area and edema volume compared with the vehicle-treated group at 24 hours after tMCAO, but there was no significant reduction in behavioral dysfunction. Twenty-four hours after pMCAO, the nicergoline-treated group showed significantly reduced infarcts, edema, and neurological scores compared with the vehicle-treated group. Decreased areas of CBF were markedly smaller in the nicergoline-treated group compared with the vehicle-treated group 24 hours after occlusion in both models. This study shows that pretreatment with nicergoline prevents brain damage, and increased CBF levels may be involved in the neuroprotective mechanism of nicergoline after acute stroke.

Changes in Cerebral Partial Oxygen Pressure and Cerebrovascular Reactivity During Intracranial Pressure Plateau Waves.

Plateau waves in intracranial pressure (ICP) are frequently recorded in neuro intensive care and are not yet fully understood. To further investigate this phenomenon, we analyzed partial pressure of cerebral oxygen (pbtO2) and a moving correlation coefficient between ICP and mean arterial blood pressure (ABP), called PRx, along with the cerebral oxygen reactivity index (ORx), which is a moving correlation coefficient between cerebral perfusion pressure (CPP) and pbtO2 in an observational study. We analyzed 55 plateau waves in 20 patients after severe traumatic brain injury. We calculated ABP, ABP pulse amplitude (ampABP), ICP, CPP, pbtO2, heart rate (HR), ICP pulse amplitude (ampICP), PRx, and ORx, before, during, and after each plateau wave. The analysis of variance with Bonferroni post hoc test was used to compare the differences in the variables before, during, and after the plateau wave. We considered all plateau waves, even in the same patient, independent because they are separated by long intervals. We found increases for ICP and ampICP according to our operational definitions for plateau waves. PRx increased significantly (p=0.00026), CPP (p<0.00001) and pbtO2 (p=0.00007) decreased significantly during the plateau waves. ABP, ampABP, and HR remained unchanged. PRx during the plateau was higher than before the onset of wave in 40 cases (73%) with no differences in baseline parameters for those with negative and positive ΔPRx (difference during and after). ORx showed an increase during and a decrease after the plateau waves, however, not statistically significant. PbtO2 overshoot after the wave occurred in 35 times (64%), the mean difference was 4.9±4.6Hg (mean±SD), and we found no difference in baseline parameters between those who overshoot and those who did not overshoot. Arterial blood pressure remains stable in ICP plateau waves, while cerebral autoregulatory indices show distinct changes, which indicate cerebrovascular reactivity impairment at the top of the wave. PbtO2 decreases during the waves and may show a slight overshoot after normalization. We assume that this might be due to different latencies of the cerebral blood flow and oxygen level control mechanisms. Other factors may include baseline conditions, such as pre-plateau wave cerebrovascular reactivity or pbtO2 levels, which differ between studies.

Early artery blood flow is more prognostic in rodent model of middle cerebral artery occlusion.

Middle cerebral artery occlusion (MCAO) by intraluminal suture is one of the most commonly used stroke models. Our previous study has indicated that the intraoperative cerebral blood flow (CBF) immediately after the stroke is prognostic for long-term permanent injury. The area of more than 50% CBF drop at the first minute after the stroke was found significantly correlated with the lesion size at 24 hours after the stroke. In order to compare the prognostic of different vessels, in this study, we further analyzed the correlation between the CBF levels in major artery, vein and the capillary bed and the lesion volume at 24 hours respectively. The results show that ipsilesional artery blood flow is of more prognostic value in MCAO lesion than the CBF in veins and capillaries.

The Specific Features of the Pathogenesis and Correction of Critical Conditions in Obstetric Care

Objective: to analyze the research areas determining the pathogenesis and correction of critical conditions in obstetric care in the past 15 years on the basis of the dissertations made at the V. A. Negovsky Research Institute of General Reanimatology. Subjects and methods. Nine hundred and twenty-nine pregnant women, parturients, and puerperas were examined; the latter were allocated to comparison groups in terms of age, weight, comorbidity, performed intensive therapy and underwent both retrospective and prospective analysis from 1981 to 2010. The comparison group comprised 44 nonobstetric patients while examining multiple organ dysfunction (MOD) in the purperas. The latter with massive blood loss were separately identified when evaluating the impaired oxygen status in patients with systemic inflammatory response syndrome and MOD. According to the pathology and indicators under study, the puerperas with MOD were examined in a few steps (2 to 7). Water sectoral disorders were detected in three steps: on days 1, 3, and 5; these were identified in four steps in case of eclamptic coma (EC), regional anesthesia, and impaired oxygen status. Results . The findings are suggestive of significant impairments in central hemodynamics (CHD) in the severe forms of gestosis, which are caused by reductions in cardiac index and circulating blood volume, the basis for these is hypovolemia. Dyshidrosis appears as an increased extracellular sector mainly due to interstitial hyperhydration. The low values of arterial blood oxygen, its delivery and uptake, oxygen extract coefficient and the high value of oxygen debt (OD) confirmed blood shunting or circulatory centralization, which was indicative of visceral hypoxia. Determination of the level of cerebral blood flow (CBF) in puerperas with coma showed its diminution due to reduced blood flow in the cortical structures. Regional anesthesia in complicated pregnancy and delivery stabilized CHD, dropped the level of proteinuria, and failed to have a negative impact on the fetus and to cause extragenital manifestations. Conclusion. The proposed algorithms for treating critical conditions in obstetric care contributed to the normalization of CHD parameters, the recovery of water sectoral balance and immune status, resulted in lower mortality rates in MOD, and could increase CBF and minimize OD, reducing the duration of comatous state in EC and the length of stay in intensive care units.

Childhood dysphasias in patients with late sequelae of perinatal central nervous system lesion

The aim of the study was to explore condition of the nervous system in different types of childhood dysphasia (CD), to compare the brain bio-electric activity to the level of cerebral blood flow, severity of neurological disorders, and neuropsychophysiological parameters, to identify the intact links of brain organization in children with minimal brain dysfunction (MBD), sensorineural hearing loss (SNHL), and spastic forms of infantile cerebral palsy (ICP). Patients and methods. 505 Children aged 4–8 years were examined: 218 with MBD, 73 with SNL, and 214 with spastic forms of ICP. The patients were divided into two groups: preschool age, 4–6 years (110 children with MBD, 29 with SNHL, and 116 with ICP) and early school age, 7–8 years (108 children with MBD, 44 with SNHL, and 98 with ICP). The group of preschool age children with spastic forms of ICP comprised 42 children with double hemiplegia (DHP), 36 with spastic hemiplegia (SHP), and 38 with spastic diplegia (SDP). The early school age group comprised 32 children with DHP, 37 with SHP, and 29 with SDP. All children underwent general clinical and neurological examination, computerized electroencephalography (EEG), neuropsychophysiological and speech testing, transcranial Doppler ultrasonography, and if required, computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. To clarify the mechanisms of cerebral disintegration in children with signs of epileptiform activity, in the day-time EEG recording, extended video-EEG monitoring was performed for 12–14 h with mandatory recording of nocturnal sleep. Condition of the audio-verbal sphere in children with SNL was examined using an original computer program, Speech_Audiometry. Results and discussion. The rate of the motor type CD upon MBD was demonstrated to be 77.6%; the mixed type CD predominated in children with SNHL and ICP: 82.2 and 66.2%, respectively. Upon spastic forms of ICP, a combination of CD with symptoms of dysarthria and oral dyspraxia was detected in 84% of cases. A mutually aggravating effect of the main clinical manifestations on the nature and intensity of speech development disorders was revealed, especially when a child had two or more active pathological processes in the CNS. A number of clinical-neurophysiological and neuropsychological correlations with different types and versions of CD were found, which allows one to perform computerized support of rehabilitation of these children and to develop differentiated approaches to treatment.

Subclinical cognitive decline in middle‐age is associated with reduced task‐induced deactivation of the brain's default mode network

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging.

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL

Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF. Twenty healthy volunteers were scanned in a test-retest approach. Independent CBV measurements for calibration were accomplished using a T1-based contrast agent steady-state method (referred to as Bookend), as well as a blood-nulling vascular space occupancy (VASO) approach. Calibrated DSC-MRI was compared with pseudo-continuous arterial spin labeling (pCASL). For segmented grey matter (GM) regions of interests (ROIs), pCASL-based CBF was 63±11ml/(min 100g) (mean±SD). Nominal CBF from non-calibrated DSC-MRI was 277±61ml/(min 100g), while calibrations resulted in 56±23ml/(min 100g) (Bookend) and 52±16ml/(min 100g) (VASO). Calibration tended to eliminate the overestimation, although the repeatability was generally moderate and the correlation between calibrated DSC-MRI and pCASL was low (r<0.25). However, using GM instead of WM ROIs for extraction of CFs resulted in improved repeatability. Both calibration approaches provided reasonable absolute levels of GM CBF, although the calibration methods suffered from low signal-to-noise ratio, resulting in weak repeatability and difficulties in showing high degrees of correlation with pCASL measurements.

Opioid receptors influence blood–/INS;brain barrier permeability, cerebral blood flow and serotonin levels following forced swimming exercise in young rats

Opioid receptors influence blood–/INS;brain barrier permeability, cerebral blood flow and serotonin levels following forced swimming exercise in young rats

Dysfunctional role of parietal lobe during self-face recognition in schizophrenia

BackgroundAnomalous sense of self is central to schizophrenia yet difficult to demonstrate empirically. The present study examined the effective neural network connectivity underlying self-face recognition in patients with schizophrenia (SZ) using [15O]H2O Positron Emission Tomography (PET) and Structural Equation Modeling. MethodsEight SZ and eight age-matched healthy controls (CO) underwent six consecutive [15O]H2O PET scans during self-face (SF) and famous face (FF) recognition blocks, each of which was repeated three times. ResultsThere were no behavioral performance differences between the SF and FF blocks in SZ. Moreover, voxel-based analyses of data from SZ revealed no significant differences in the regional cerebral blood flow (rCBF) levels between the SF and FF recognition conditions. Further effective connectivity analyses for SZ also showed a similar pattern of effective connectivity network across the SF and FF recognition. On the other hand, comparison of SF recognition effective connectivity network between SZ and CO demonstrated significantly attenuated effective connectivity strength not only between the right supramarginal gyrus and left inferior temporal gyrus, but also between the cuneus and right medial prefrontal cortex in SZ. ConclusionThese findings support a conceptual model that posits a causal relationship between disrupted self–other discrimination and attenuated effective connectivity among the right supramarginal gyrus, cuneus, and prefronto-temporal brain areas involved in the SF recognition network of SZ.

Two-Photon Imaging of Blood Flow in the Rat Cortex

Cerebral blood flow plays a central role in maintaining homeostasis in the brain, and its dysfunction leads to pathological conditions such as stroke. Moreover, understanding the dynamics of blood flow is central to the interpretation of data from imaging modalities--such as intrinsic optical signaling and functional magnetic resonance imaging--that rely on changes in cerebral blood flow and oxygen level to infer changes in the underlying neural activity. Recent advances in imaging techniques have allowed detailed studies of blood flow in vivo at high spatial and temporal resolutions. We discuss techniques to accurately measure cerebral blood flow at the level of individual blood vessels using two-photon laser-scanning microscopy. By directing the scanning laser along a user-defined path, it is possible to measure red blood cell (RBC) velocity and vessel diameter across multiple vessels simultaneously. The combination of these measurements permits accurate assessment of total flux with sufficient time resolution to measure fast modulations in flux, such as those caused by heartbeat, as well as slower signals caused by vasomotion and hemodynamic responses to stimulus. Here, we discuss general techniques for animal preparation and measurement of blood flow with two-photon microscopy. We incorporate extensions to existing methods to accurately acquire flux data simultaneously across multiple vessels in a single trial. Central to these measurements is the ability to generate scan paths that smoothly connect user-defined lines of interest while maintaining high accuracy of the scan path.

The relationship between cognitive impairment and cerebral blood flow changes after transient ischaemic attack

Objective: The associations between cognitive impairment following the initial onset of transient ischaemic attack (TIA) and the parameters of altered cerebral blood flow and high-sensitivity C-reactive protein (HsCRP) level are unclear.Methods: A total of 97 first-time TIA patients aged 69·94±4·02 years (38–75 years; M:F, 50:47) hospitalized between March 2010 and July 2011 were compared to 100 healthy control patients aged 66·56±12·15 years (45–80 years; M:F, 60:40). Cognitive function was quantified by Montreal Cognitive Assessment (MoCA). Intracranial blood flow was measured using transcranial Doppler ultrasound, and HsCRP levels were assessed using the Spearman correlation coefficient. Relationships between both values and MoCA scores were examined.Results: Transient ischaemic attack patients exhibited declined cognitive function manifested as impaired verbal fluency (97·93%), memory recall (91·75%), abstraction (84·53%), and visuospatial/executive abilities (79·38%). To a lesser degree, TIA patients also evidenced abnormalities in attention (50·52%), naming (20·62%), and orientation (20·62%). Furthermore, MoCA scores significantly correlated with high HsCRP levels and low vascular systolic peak velocities (P<0·001). Vascular systolic peak velocities were high in nine patients (9·23%) and low in 57 patients (58·76%). Thus, cognitive impairment was closely related to HsCRP levels and intracranial blood flow velocities.Conclusion: Post-TIA cognitive impairment may result from atherosclerosis and reduced blood flow to the brain. Cognitive impairment, transcranial Doppler-visualized changes, and elevated HsCRP levels are important diagnostic indicators of TIA. Markers provided by cognitive evaluation of TIA patients following the initial onset of TIA may allow clinicians to better predict and prevent adverse vascular events.

Lipoprotein Receptor–Related Protein-6 Protects the Brain From Ischemic Injury

Loss-of-function mutations of the lipoprotein receptor-related protein-6 (LRP6), a coreceptor in the Wingless-related integration site-β-catenin prosurvival pathway, have been implicated in myocardial ischemia and neurodegeneration. However, it remains to be established whether LRP6 is also involved in ischemic brain injury. We used LRP6+/- mice to examine the role of this receptor in the mechanisms of focal cerebral ischemia. Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery. Motor deficits and infarct volume were assessed 3 days later. Glycogen-synthase-kinase-3β (GSK-3β) phosphorylation was examined by Western blotting with phosphospecific antibodies, and the mitochondrial membrane potential changes induced by Ca2+ were also assessed. LRP6+/- mice have larger stroke and more severe motor deficits, effects that were independent of intraischemic cerebral blood flow, vascular factors, or cytosolic β-catenin levels. Rather, LRP6 haploinsufficiency increased the activating phosphorylation and decreased the inhibitory phosphorylation of GSK-3β, a kinase involved in proinflammatory signaling and mitochondrial dysfunction. Accordingly, postischemic inflammatory gene expression was enhanced in LRP6+/- mice. Furthermore, the association of mitochondria with activated GSK-3β was increased in LRP6+/- mice, resulting in a reduction in the Ca2+ handling ability of mitochondria. The mitochondrial dysfunction was reversed by pharmacological inhibition of GSK-3β. LRP6 activates an endogenous neuroprotective pathway that acts independently of β-catenin by controlling GSK-3β activity and preventing its deleterious mitochondrial and proinflammatory effects. The findings raise the possibility that emerging treatment strategies for diseases attributable to LRP6 loss-of-function mutations could also lead to new therapeutic avenues for ischemic stroke.

A Selective Insular Perfusion Deficit Contributes to Compromised Salience Network Connectivity in Recovering Alcoholic Men

Alcoholism can disrupt neural synchrony between nodes of intrinsic functional networks that are maximally active when resting relative to engaging in a task, the default mode network (DMN) pattern. Untested, however, are whether the DMN in alcoholics can rebound normally from the relatively depressed task state to the active resting state and whether local perfusion deficits could disrupt network synchrony when switching from conditions of rest to task to rest, thereby indicating a physiological mechanism of neural network adaptation capability. Whole-brain, three-dimensional pulsed-continuous arterial spin labeling provided measurements of regional cerebral blood flow (CBF) in 12 alcoholics and 12 control subjects under three conditions: pretask rest, spatial working-memory task, and posttask rest. With practice, alcoholics and control subjects achieved similar task accuracy and reaction times. Both groups exhibited a high-low-high pattern of perfusion levels in DMN regions during the rest-task-rest runs and the opposite pattern in posterior and cerebellar regions known to be associated with spatial working memory. Alcoholics showed selective differences from control subjects in the rest-task-rest CBF pattern in the anterior precuneus and CBF level in the insula, a hub of the salience network. Connectivity analysis identified activation synchrony from an insula seed to salience nodes (parietal, medial frontal, anterior cingulate cortices) in control subjects only. We propose that attenuated insular CBF is a mechanism underlying compromised connectivity among salience network nodes. This local perfusion deficit in alcoholics has the potential to impair ability to switch from cognitive states of interoceptive cravings to cognitive control for curbing internal urges.

Age-related alteration in cerebral blood flow and energy failure is correlated with cognitive impairment in the senescence-accelerated prone mouse strain 8 (SAMP8)

Cerebrovascular dysfunction is an early pathogenic event in Alzheimer's disease (AD) and plays a key role in the disease process. Cerebral hypoperfusion, brain glucose hypometabolism and disrupted blood-brain barrier (BBB) integrity contributed to the onset and progression of AD. However, the relationships between the age-related cognitive impairment and cerebral blood flow (CBF), energy metabolism and BBB have not been clearly explained. In this study, we investigated the cognitive function, CBF, BBB damage and expression level of glucose transporter (GLUT) 1 and 3 of senescence-accelerated mouse prone 8 (SAMP8), and the correlations between each of them were analyzed. When compared with SAMR1 (senescence-accelerated mouse resistant 1), the cognitive abilities of SAMP8 were damaged apparently even at 4 months of age, showing up a slower and more capricious acquisition in Morris water maze tasks. In both SAMP8 and SAMR1, reduced CBF and increased BBB leakage were observed with increasing age, but an earlier and more severe impairment was detected in SAMP8. In addition, alterations of GLUT1 and GLUT3 protein expression in cortex and hippocampus were more prominent in SAMP8. Correlation analysis demonstrated that the increased escape latency was correlated negatively with CBF and expression of glucose transporters; and positively with BBB permeability in the hippocampus. These results suggested that CBF, BBB integrity, the expression of GLUT1 and GLUT3 were significantly affected by age and strain, which were also closely associated with cognitive ability. The alteration in CBF and energy failure induced by aging and vascular insults resulted in cognitive decline in SAMP8.

Cerebral Blood Flow Changes after Brain Injury in Human Amyloid-Beta Knock-in Mice

Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer's disease (AD). Increased brain concentrations of amyloid-β (Aβ) peptides and impaired cerebral blood flow (CBF) are shared pathologic features of TBI and AD and promising therapeutic targets. We used arterial spin-labeling magnetic resonance imaging to examine if CBF changes after TBI are influenced by human Aβ and amenable to simvastatin therapy. CBF was measured 3 days and 3 weeks after controlled cortical impact (CCI) injury in transgenic human Aβ-expressing APP(NLh/NLh) mice compared to murine Aβ-expressing C57Bl/6J wild types. Compared to uninjured littermates, CBF was reduced in the cortex of the injured hemisphere in both Aβ transgenics and wild types; deficits were more pronounced in the transgenic group, which exhibited injury-induced increased concentrations of human Aβ. In the hemisphere contralateral to CCI, CBF levels were stable in Aβ transgenic mice but increased in wild-type mice, both relative to uninjured littermates. Post-injury treatment of Aβ transgenic mice with simvastatin lowered brain Aβ concentrations, attenuated deficits in CBF ipsilateral to injury, restored hyperemia contralateral to injury, and reduced brain tissue loss. Future studies examining long-term effects of simvastatin therapy on CBF and chronic neurodegenerative changes after TBI are warranted.

Effect of angiotensin II on spatial memory, cerebral blood flow, cholinergic neurotransmission, and brain derived neurotrophic factor in rats

Studies have shown the involvement of angiotensin II (Ang II) in neurobehavioral aspects, but the exact role of Ang II in memory is still ambiguous. This study explored the effect of central Ang II on spatial memory along with cholinergic neurotransmission, brain energy metabolism, cerebral blood flow (CBF), and brain-derived neurotrophic factor (BDNF) in rats. Spatial memory was evaluated by Morris water maze (MWM) after Ang II (ICV) administration in male Sprague-Dawley rats. CBF was measured by laser Doppler flowmetry. Oxidative stress adenosine triphosphate (ATP), BDNF, acetylcholinesterase (AChE), and acetylcholine (ACh) were estimated in the cortex and hippocampus at 1, 24, and 48h after Ang II administration. The effect of AT1 and AT2 receptor blocker (candesartan and PD123,319, respectively), AChE inhibitor (donepezil), and antioxidant melatonin was studied on memory, CBF, and biochemical parameters. Ang II caused spatial memory impairment by affecting acquisition, consolidation, and recall in the MWM test along with a significant reduction in CBF. Ang II significantly reduced ACh level and caused oxidative stress in the rat brain 1h post-injection. No significant change was observed in BDNF, AChE, and ATP level. Candesartan and donepezil prevented Ang II-induced memory impairment, reduction in CBF and ACh level. However, PD123,319 and melatonin failed to prevent Ang II-induced memory impairment but improved CBF partially. This study suggests that Ang II, via the AT1 receptor, affects spatial memory formation, CBF, and ACh level while AT2 receptor has no significant role.

Identifying and utilizing the ischemic penumbra

The penumbral concept is defined as different areas within the ischemic region evolve into irreversible brain injury over time and that this evolution is most critically linked to the severity of the decline in cerebral blood flow (CBF). The ischemic penumbra was initially defined as a region of reduced CBF with absent spontaneous or induced electrical potentials that still maintained ionic homeostasis and transmembrane electrical potentials. The reduction of CBF levels to between 10 and 15 mL/100 g/min and approximately 25 mL/100 g/min are likely to identify penumbral tissue, and the ischemic core of irreversible ischemic tissue has a CBF value below the lower threshold. The role of identifying this critically deprived brain tissue from CBF in triaging patients for endovascular ischemic therapy is evolving. In this review we focus on the basic science of the penumbral concept and identification using various imaging modalities (PET, MRI, and CT) in animal models and human studies. Another article in this supplement addresses the clinical implication and the current understanding and application of this concept into clinical practice of endovascular ischemic stroke therapy.