Augmentation Of Cerebral Blood Flow Research Articles

A Pilot Study to Examine the Effect of Passive Straight Leg Raise Performed During Cardiopulmonary Resuscitation on Cerebral Perfusion Measured by Noninvasive Cerebral Oximetry.

This was a double cross-over physiologic efficacy randomized study. Study in 10 subjects with in-hospital cardiac arrest for whom CPR was undertaken. Subjects were randomized to receive two cycles of CPR with PLR followed by two cycles of CPR without PLR (Group I) or vice-versa (Group II). Subjects had their foreheads (right and left) fitted with near infrared spectroscopy (NIRS) electrodes (O3 System-Masimo, Masimo corporation Forty Parker, Irvine CA) while undergoing CPR during the study. NIRS readings, a measure of mixed venous, arterial, and capillary blood oxygen saturation, act as a surrogate measure of cerebral blood perfusion during CPR. PLR was randomly used "first" in five of them, whereas it was used "second" in the remaining five subjects. In subjects in whom PLR was performed during first two cycles (Group I), NIRS values were initially significantly greater. The performance of PLR during CPR in Group II attenuated the decline in NIRS readings during CPR. PLR during CPR is feasible and leads to augmentation of cerebral blood flow. Furthermore, the expected decline in cerebral blood flow over time during CPR may be attenuated by this maneuver. The clinical significance of these findings will require further investigations.

Influence of Exercise Modality on the Cerebrovascular Response to Physiological Stressors

BackgroundHabitual exercise has previously been shown to alter the cerebrovascular response to hypercapnia. Similar to hypercapnia, increases in the brain’s metabolic activity result in local augmentation of cerebral blood flow; however, the mechanisms governing the cerebrovascular response to these two stimuli likely differ. Although, previous studies have examined the influence of aerobic exercise on the cerebrovascular response to hypercapnia, little is known about the influence of habitual resistance training on cerebrovascular function. Therefore, the purpose of this study was to evaluate the cerebrovascular response to both hypercapnia and a metabolic stimulus (cognitive challenge) in resistance trained (RT), aerobic trained (AT), and untrained (UT) adults.MethodsWe recruited 13 RT (women: n = 2, age: 24 ± 4 y), 12 AT (women: n = 2, age: 28 ± 6 y), and 13 UT (women: n = 2, age: 27 ± 5 y) healthy young adults. Middle cerebral artery velocity (MCAv), beat‐to‐beat mean arterial blood pressure (MAP) and end‐tidal carbon dioxide (ETCO2) were continuously monitored during hypercapnia and a Stroop Color and Word Test. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Reactivity to hypercapnia was calculated as the slope of the relationship between each variable of interest (MCAv or CVCi) and ETCO2. Responses to the Stroop test were calculated as the absolute change from baseline to the 3‐beat peak of each variable during the test.ResultsThere were no significant differences in MCAv reactivity and CVCi reactivity to hypercapnia between groups. Despite all groups having a similar change in MAP and ETCO2 during the Stroop test, RT individuals had a greater increase in MCAv (RT: 18.1 ± 1.9 cm/s, AT: 9.7 ± 1.5 cm/s, UT: 15.7 ± 2.0 cm/s; AT vs. RT p < 0.01; AT vs. UT p = 0.07) and CVCi (RT: 0.15 ± 0.02 cm/s/mmHg, AT: 0.08 ± 0.02 cm/s/mmHg, UT: 0.12 ± 0.02 cm/s/mmHg; AT vs. RT p = 0.05; AT vs. UT p = 0.28) compared with AT individuals during the Stroop test. While there was a positive association between the MCAv response to hypercapnia and the MCAv response to the Stroop test in AT individuals (r = 0.67, p < 0.05), and a trend for association in UT individuals (r = 0.49, p = 0.09), there was no relationship between the two variables in RT individuals (r = 0.18, p = 0.56).ConclusionWhile exercise modality did not influence the cerebrovascular response to hypercapnia, it did influence the response to a metabolic stimulus, such that RT individuals had a greater MCAv and CVCi response to a cognitive challenge, compared with AT individuals. Further, exercise modality may influence the mechanisms by which the cerebrovasculature of young adults responds to physiological stimuli.Support or Funding InformationSupported by National Institute of Health grant HL118154

Abstract WP171: Are We Correctly Measuring Cerebrovascular Reserve Capacity: A Study on Multiple Sequential Post-Acetazolamide Injection Cerebral Blood Flow Measurements Using Arterial Spin Labeling in a Moyamoya Patient Population?

Introduction: Cerebrovascular reserve capacity (CVRC), an important predictor and prognostic factor for patients with moyamoya disease (MMD), can be derived by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Commonly, a single CBF measurement is performed after ACZ injection at a time point varying between 5 to 20 minutes, whereas the dynamic temporal response using sequential CBF measurements has not been studied extensively. Furthermore, current literature reports group averaged CVRCs with high standard deviations indicating a patient-specific CVRC is spread over a wide range of values. The aim of this study was to assess the temporal dynamic response of CBF and derived CVRC during the ACZ challenge using arterial spin labeling in patients with MMD. Methods: Ten patients with MMD were included before and/or after revascularisation surgery and examined on a 3T MR scanner. CBF maps, based on 3D-pseudocontineous arterial spin labeling, were acquired before and 5, 15 and 25 minutes after an i.v. ACZ injection and registered to each patient’s 3D-T1-weighted image. A vascular territory template was spatially normalised to patient-specific space, defined by the 3D-T1-weighted image, including bilateral ACA, MCA and PCA. A post label delay of 2500 ms and large regions-of-interests were used to account for possible arterial transit time artefacts. CVRC was calculated as CBF augmentation post-ACZ injection relative to baseline. Results: A total of sixteen examinations were analysed. Average peak CBF augmentation occurred at 5 min post-ACZ injection, successively decreasing at 15 - and 25 min post-ACZ injection . CVRC followed a similar pattern. Peak CBF augmentation mostly occurred at 5 min for all vascular regions (frequency distribution 5 min: 64 %, 15 min: 23 %, 25 min: 13 %). Average ratio between CVRC calculated using 15 min CBF augmentation and CVRC using true peak CBF augmentation (5, 15 or 25 min) was 0.80 to 0.90 for all vascular regions. Conclusion: CVRC assessed using 15 min as a single post-ACZ injections time point may underestimate CVRC in average by 10 % to 20 % because of individual temporal patient response. The use of multiple post-injection time points is warranted.

CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage.

Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI. CBF was assessed by bedside xenon-enhanced CT at days 0-3, 4-7, and 8-12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group. In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1-33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2-46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9-48.5) at baseline and 31.6 (IQR 22.4-35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients. Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

Cerebral blood flow augmentation using a cardiac-gated intracranial pulsating balloon pump in a swine model of elevated ICP.

Augmenting brain perfusion or reducing intracranial pressure (ICP) dose is the end target of many therapies in the neuro-critical care unit. Many present therapies rely on aggressive systemic interventions that may lead to untoward effects. Previous studies have used a cardiac-gated intracranial balloon pump (ICBP) to model hydrocephalus or to flatten the ICP waveform. The authors sought to sought to optimize ICBP activation parameters to improve cerebral physiological parameters in a swine model of raised ICP. The authors developed a cardiac-gated ICBP in which the volume, timing, and duty cycle (time relative to a single cardiac cycle) of balloon inflation could be altered. They studied the ICBP in a swine model of elevated ICP attained by continuous intracranial fluid infusion with continuous monitoring of systemic and cerebral physiological parameters, and defined two specific protocols of ICBP activation. Eleven swine were studied, 3 of which were studied to define the optimal timing, volume, and duty cycle of balloon inflation. Eight swine were studied with two defined protocols at baseline and with ICP gradually raised to a mean of 30.5 mm Hg. ICBP activation caused a consistent modification of the ICP waveform. Two ICBP activation protocols were used. Balloon activation protocol A led to a consistent elevation in cerebral blood flow (8%-25% above baseline, p < 0.00001). Protocol B resulted in a modest reduction of ICP over time (8%-11%, p < 0.0001) at all ICP levels. Neither protocol significantly affected systemic physiological parameters. The preliminary results indicate that optimized protocols of ICBP activation may have beneficial effects on cerebral physiological parameters, with minimal effect on systemic parameters. Further studies are warranted to explore whether ICBP protocols may be of clinical benefit in patients with brain injuries with increased ICP.

Antidepressant pharmacotherapy and poststroke motor rehabilitation: A review of neurophysiologic mechanisms and clinical relevance.

According to the National Stroke Association, stroke is the leading cause of adult disability in the United States, where it is estimated that about 795,000 strokes occur on an annual basis. Minimizing the disability burden of a stroke routinely involves behavioral therapies such as physical and occupational therapy, as well as pharmacologic interventions. The positive effect of antidepressants on functional outcomes for patients with poststroke depression is well known and practiced. In the past 15 years, a growing body of evidence has demonstrated that antidepressant pharmacotherapy and selective serotonin reuptake inhibitors specifically have a role in the functional recovery from strokes even in the nondepressed population. The mechanisms by which antidepressants improve motor recovery following stroke are multifactorial, but it is clear that the process involves augmentation of cerebral blood flow, cortical excitation, and potentiation of neural growth factors all resulting in enhancement of neurogeneration. This review will examine the existing evidence and mechanisms behind antidepressant use for motor recovery in stroke patients and discuss the major human clinical trials that have been conducted surrounding this topic. The evidence clearly suggests that antidepressants have a positive impact on poststroke functional recovery regardless of the presence of depression, and although large-scale randomized, controlled trials are still ongoing, antidepressants are emerging as a promising pharmaceutical means of actively lessening the burden of disability following stroke.

P.054 Bone marrow transplant restores Cerebrovascular Reactivity (CVR) in Sickle Cell Disease (SCD): a case presentation

Background: A diagnosis of SCD in childhood confers a 200-fold increase in the risk of arterial ischemic stroke. Blood flow velocity measures provide better identification of ischemic risk compared to angiography. This indicates that steno-occlusive arteriopathy is not the singular causative factor. Cerebrovascular reactivity allows for augmentation of cerebral blood flow when needed. Kosinski et al in 2016 demonstrated a direct correlation between CVR and hematocrit levels in SCD. We report a case where CVR persistently normalized in an SCD patient following bone marrow transplant therapy (BMT). Methods: A nine-month-old SCD patient presented with right AIS. Angiography revealed a bilateral Moya-Moya like arteriopathy. A TCD study was normal while a CVR-MRI study revealed markedly impaired reactivity in the entire anterior circulation. Haemaglobin-S at that time was 20.2 %. BMT was performed at age four due to frequent sickle cell crises. Results: One year post-transplant, CVR had dramatically improved in areas previously shown to have impairment (haemoglobin-S 0%). Neuroimaging five years post-transplant showed no further arteriopathy and persistently normalized CVR. Conclusions: BMT therapy resulted in the arrest of progressive intracranial arteriopathy and persistently restored vascular reserve. SCD might not only produce global hematological effects but also triggers local processes such as endothelial dysfunction and vascular inflammation that impair cerebrovascular function.

Abstract WMP27: Cerebral Blood Velocity Changes During Dobutamine Administration for Experimental Subarachnoid Hemorrhage in Mice

Introduction: Hyperdynamic therapy with dobutamine (DOB) administration on patients with subarachnoid hemorrhage (SAH) is a useful strategy for treating cerebral vasospasm and neurological deterioration. Even some reports have suggested that DOB administration caused the cerebral blood flow (CBF) augmentation by increasing cardiac output, microcirculatory behavior in brain remains unclear. Hypothesis: Red blood cell (RBC) velocity should be increased under DOB administration. To investigate the cortical microcirculation, two-photon laser scanning microscopy with successive line-scans was used for red blood cell (RBC) velocity estimation. Methods: SAH was induced in ten male wild-type C57BL/6 mice (23 - 25g) using endovascular perforation technique. Five days after SAH, a cranial window was prepared for optical access to the cortical vasculature. Then we observed two-photon microscopy with intravenously injected rhodamine-dextran. The RBC velocity was visualized as dark objects against the fluorescent plasma background. The velocity was estimated from dark objects angle in successive line-scans analyzed by Radon function based algorithm. DOB was administrated intravenously at the dose of 6 and 12 μg/kg/min. Results: RBC velocity was increased in 8 mice after the DOB administration and 2 mice were reduced. The RBC velocity in increased mice of baseline , 6 , and 12 μg/kg/min was 1.29±0.40, 1.70±0.74 and 1.37±0.53 mm/sec, respectively. In the reduced mice, the RBC velocity was dropped almost half value of baseline at the DOB administration. Conclusions: DOB administration was increased RBC velocity in cortical microcirculation. It indicates DOB hyperdynamic therapy on patients with SAH is effective in the viewpoint of cortical microcirculatory control.

Transcranial Doppler-guided cerebral blood flow augmentation resulting in near complete resolution of cerebral infarct: A case report of intractable intracranial hypertension

AbstractIntractable intracranial hypertension is a nerve wrecking clinical challenge which is associated with high morbidity and mortality. Barbiturate coma therapy (BCT) is one of the recommended options for such a challenge but is associated with its own set of complications. Multimodality monitoring is a new advent in neurocritical care and provides a new vision to judiciously cater to such challenges. We hereby report a case of successfully treating intractable intracranial hypertension after maximal possible surgical decompression and evidence of well-formed cerebral ischaemic zones with intracranial multimodality monitoring guided BCT. The positive outcome was to the extent of almost complete reversal of cerebral ischaemic zones and return to normal life schedule.

A retrospective pilot study of correlation of cerebral augmentation effects of external counterpulsation with functional outcome after acute ischaemic stroke

ObjectiveExternal counterpulsation (ECP) is a non-invasive method used to augment cerebral blood flow of patients with ischaemic stroke via induced hypertension. We aimed to explore the correlation between the cerebral blood flow augmentation effects induced by ECP and clinical outcome after acute ischaemic stroke.MethodsWe retrospectively analysed our ECP registry of patients with ischaemic stroke who were enrolled within 7 days after stroke onset. Bilateral middle cerebral arteries of patients were monitored using transcranial Doppler (TCD). Flow velocity changes before, during and after ECP were, respectively, recorded for 3 min. The cerebral augmentation index (CAI) was the increase in percentage of the middle cerebral artery mean flow velocity during ECP compared with baseline. TCD data were analysed based on the side ipsilateral or contralateral to the infarct. The modified Rankin Scale (mRS) (good outcome: mRS 0∼2; poor outcome: mRS 3∼6) was evaluated 6 months after the index stroke.Results72 patients were included (mean age, 63.8±10.7 years; 87.5% males). At month 6 after stroke onset, univariate analysis showed that the National Institutes of Health Stroke Scale at recruitment was significantly higher and ECP therapy duration was longer in the poor outcome group, while the ipsilateral CAI was significantly lower in the good outcome group than that in the poor outcome group (3.71±4.94 vs 7.73±7.66, p=0.044). Multivariate logistic regression showed that ipsilateral CAI was independently correlated with an unfavourable functional outcome after adjusting for confounding factors.ConclusionsThe higher degree of cerebral blood flow velocity augmentation on the side ipsilateral to the infarct induced by ECP is independently correlated with an unfavourable functional outcome after acute ischaemic stroke.

Enhancing cerebral perfusion with external counterpulsation after ischaemic stroke: how long does it last?

ObjectiveExternal counterpulsation (ECP) is a non-invasive method used to augment cerebral perfusion in ischaemic stroke. We aimed to investigate time-course effects on blood pressure elevation and cerebral blood flow augmentation...

Cerebral blood flow augmentation by external counterpulsation enhances corticomotor excitability in subacute stroke patients: a randomized controlled trial

Cerebral blood flow augmentation by external counterpulsation enhances corticomotor excitability in subacute stroke patients: a randomized controlled trial

P345: Effects of cerebral blood flow augmentation by external counterpulsation on corticomotor excitability in subacute stroke patients: preliminary results

P345: Effects of cerebral blood flow augmentation by external counterpulsation on corticomotor excitability in subacute stroke patients: preliminary results

Low neurologic intensive care unit hemoglobin as a predictor for intra-arterial vasospasm therapy and poor discharge modified Rankin Scale in aneurysmal subarachnoid haemorrhage-induced cerebral vasospasm

BackgroundIntra-arterial vasospasm therapy (IAVT) with vasodilators, balloon angioplasty, and cerebral blood flow augmentation devices are therapies for aneurysmal subarachnoid hemorrhage-induced symptomatic cerebral vasospasm refractory to maximal medical management. Our aim...

Intra-aortic balloon pump (IABP) counterpulsation improves cerebral perfusion in patients with decreased left ventricular function

The current goal of treatment after acute ischemic stroke is the increase of cerebral blood flow (CBF) in ischemic brain tissue. Intra-aortic balloon pump (IABP) counterpulsation in the setting of cardiogenic shock is able to reduce left ventricular afterload and increase coronary blood flow. The effects of an IABP on CBF have not been sufficiently examined. We hypothesize that the use of an IABP especially enhances cerebral blood flow in patients with pre-existing heart failure. In this pilot study, 36 subjects were examined to investigate the effect of an IABP on middle cerebral artery (MCA) transcranial Doppler (TCD) flow velocity change and relative CBF augmentation by determining velocity time integral changes (ΔVTI) in a constant caliber of the MCA compared to a baseline measurement without an IABP. Subjects were divided into two groups according to their left ventricular ejection fraction (LVEF): Group 1 LVEF >30% and Group 2 LVEF ≤30%. Both groups showed an increase in CBF using an IABP. Patients with a LVEF ≤30% showed a significantly higher increase of ΔVTI in the MCA under IABP augmentation compared to patients with a LVEF >30% (20.9% ± 3.9% Group 2 vs.10.5% ± 2.2% Group 1, p<0,05). The mean arterial pressure (MAP) increased only marginally in both groups under IABP augmentation. IABP improves cerebral blood flow, particularly in patients with pre-existing heart failure and highly impaired LVEF. Hence, an IABP might be a treatment option to improve cerebral perfusion in selected patients with cerebral misperfusion and simultaneously existing severe heart failure.

Efficacy of NeuroFlo Device in Treatment of Patients with Atrial Fibrillation

Atrial fibrillation (AF) is a well-established independent risk factor for stroke. We examined cerebral blood flow augmentation in the treatment of acute ischemic stroke (AIS) in patients with AF by performing secondary analysis of data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial, a randomized controlled trial evaluating NeuroFlo treatment in stroke patients within 14 hours of symptom onset. We report subgroup analyses of outcomes in SENTIS patients with a history or new diagnosis of AF. Among patients with AF, those treated with NeuroFlo demonstrated significant improvement over those not treated for multiple end points: global efficacy end point (P=.030), modified Rankin Scale (mRS) score 0-2 versus 3-6 (P=.029), and stroke-related mortality (P=.015). There was a significant improvement in global end point for those aged 60 years or older (P=.042) and 80 years or older (P=.017), with a trend toward improvement for age 70 years or older (P=.055), and significant improvement in those who achieved good outcomes (mRS score 0-2 versus 3-6) at age 60 years or older (P=.038), 70 years or older (P=.022), and 80 years or older (P=.008). NeuroFlo treatment in stroke patients with AF resulted in significantly better outcomes compared with nontreated patients with AF. Collateral flow recruitment, maintenance of cerebral blood flow around stroke core, and improvement of penumbral blood flow are potential mechanisms for these improved outcomes. NeuroFlo may represent a valid therapeutic option for patients with AF and AIS, and therefore, future trials of the device are warranted.

Abstract W P55: The Degree of Cerebral Blood Flow Augmentation by External Counterpulsation Correlates With Clinical Outcome After Acute Ischemic Stroke

Background and Purpose: External counterpulsation (ECP) is a novel noninvasive method used to augment cerebral blood flow which may benefit ischemic stroke patients. We aimed to explore the association between the degree of cerebral blood flow augmentation by ECP and clinical outcome after acute ischemic stroke. Methods: Acute ischemic stroke patients within 7 days of symptom onset were recruited into this study. On admission, bilateral middle cerebral arteries of subjects were monitored using transcranial Doppler (TCD). Flow velocity changes before, during, and after ECP were, respectively, recorded for 3 minutes. Cerebral augmentation index (CAI) was the increase in percentage of middle cerebral artery mean flow velocity during ECP compared with baseline. TCD data were analyzed based on ipsilateral or contralateral to the infarct side. Modified Rankin Scale (mRS) was evaluated 3 months, 6 months and 1 year after ischemic stroke onset. We stratified the patients into two groups (good outcome: mRS 0~2; poor outcome: mRS 3~6) at each measurement time point. Results: 72 patients were recruited (mean age, 63.8±10.7 years; 87.5% males). At month 6 and year 1 after stroke onset, univariate analysis showed that admission National Institutes of Health Stroke Scale (NIHSS) was significantly lower and ECP therapy duration was longer in good outcome group; while the ipsilateral CAI was significantly lower in good outcome group than those in poor outcome group (3.71±4.94 versus 7.73±7.66, P=0.044; 3.50±4.73 versus 8.58±7.72, P=0.015 respectively). Multivariate logistic regression showed that ipsilateral CAI and baseline NIHSS were independent predictors for a favourable outcome at these two measurement points. Conclusions: The degree of cerebral augmentation on ipsilateral to the infarct side by ECP is found to be an important predictor for long-term good outcome in acute ischemic stroke patients, in addition to the well-known prognostic factors such as NIHSS.

Effects of intravenous administration of umbilical cord blood CD34+ cells in a mouse model of neonatal stroke

Neonatal stroke occurs in approximately 1/4000 live births and results in life-long neurological impairments: e.g., cerebral palsy. Currently, there is no evidence-based specific treatment for neonates with stroke. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment in rodent models of neonatal brain injury. However, all of the studies examined the effects of administering either the UCB mononuclear cell fraction or UCB-derived mesenchymal stem cells in neonatal rat models. The objective of this study was to examine the effects of human UCB CD34+ cells (hematopoietic stem cell/endothelial progenitor cells) in a mouse model of neonatal stroke, which we recently developed. On postnatal day 12, immunocompromized (SCID) mice underwent permanent occlusion of the left middle cerebral artery (MCAO). Forty-eight hours after MCAO, human UCB CD34+ cells (1×105cells) were injected intravenously into the mice. The area in which cerebral blood flow (CBF) was maintained was temporarily larger in the cell-treated group than in the phosphate-buffered saline (PBS)-treated group at 24h after treatment. With cell treatment, the percent loss of ipsilateral hemispheric volume was significantly ameliorated (21.5±1.9%) compared with the PBS group (25.6±5.1%) when assessed at 7weeks after MCAO. The cell-treated group did not exhibit significant differences from the PBS group in either rotarod (238±46s in the sham-surgery group, 175±49s in the PBS group, 203±54s in the cell-treated group) or open-field tests. The intravenous administration of human UCB CD34+ cells modestly reduced histological ischemic brain damage after neonatal stroke in mice, with a transient augmentation of CBF in the peri-infarct area.

Protective arms of the renin–angiotensin‐system in neurological disease

In recent years it has been firmly established that apart from the classic renin-angiotensin system (RAS) comprising angiotensin (Ang) II, angiotensin converting enzyme (ACE; responsible for AngII generation) and the angiotensin AT1 receptor (AT1 R), there also exist protective arms of the RAS that comprise the angiotensin AT2 receptor (AT2 R), Ang-(1-7), ACE2 (mainly responsible for Ang-(1-7) synthesis) and Mas, the receptor for Ang-(1-7). Stimulation of AT2 R promotes neuronal differentiation, neurite outgrowth and axonal regeneration, which results in an acceleration of repair and improved functional outcome after injury of peripheral nerves or the spinal cord. Stimulation of AT2 R and the receptor Mas has been shown to reduce infarct size and ameliorate neurological deficits in various animal models of stroke. The underlying mechanisms of action are comprised of activation of direct neurotrophic, anti-inflammatory and anti-oxidant pathways, as well as the augmentation of cerebral blood flow. Cognitive function is improved by AT2 R stimulation due, at least in part, to increased cerebral blood flow. There is indirect evidence that Ang-(1-7) could also play a role in protection against cognitive decline, but studies confirming this have not yet been published. In view of the data reviewed in this article, it can be assumed that the protective arms of the RAS are putative targets in the treatment of neurological diseases, which involve tissue damage or cognitive impairment.

Effects of Age on Outcome in the SENTIS Trial: Better Outcomes in Elderly Patients

Background: Increasing age is associated with poor outcome after stroke. The Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial explored the augmentation of collateral circulation to the ischemic penumbra as a novel approach to stroke treatment. The aim of this post hoc analysis was to examine the effect of age on outcomes in the SENTIS trial. Methods: Using data from the randomized controlled SENTIS trial, we explored outcomes of cerebral blood flow augmentation using the NeuroFlo™ device in patients categorized by age strata at 70 and 80 years. We evaluated outcomes of overall serious adverse event (SAE) and intracerebral hemorrhage (ICH) rates, freedom from all-cause and stroke-related mortality, and independent functional outcome as defined by the modified Rankin Scale score (mRS ≤2). Results: The SENTIS as-treated cohort included 251 patients ≥70 years and 107 patients ≥80 years. Elderly SENTIS patients included a higher percentage of women and Caucasians than the younger group. Patients in the older group more frequently had vascular risk factors including hypertension, previous stroke, transient ischemic attacks and atrial fibrillation. However, baseline risk-factor profile, stroke severity, and time to randomization did not differ between the treated and nontreated elderly patients. The older patients treated with NeuroFlo had significantly higher chances for survival and for obtaining an independent functional state (mRS ≤2) compared with those who were not treated. Rates of SAEs and ICHs did not differ between the treatment groups. Conclusions: NeuroFlo treatment is safe and results in better outcomes for elderly patients. This may be the result of recruitment and support of already existing collateral systems in these patients.