Automated Brain Perfusion Imaging in Acute Ischemic Stroke: Interpretation Pearls and Pitfalls

Maybe there is something in here to 100% recovery but it's not obvious to me.

Automated Brain Perfusion Imaging in Acute Ischemic Stroke: Interpretation Pearls and Pitfalls

 

Manal Nicolas-Jilwan

,

Max Wintermark

Originally published27 Sep 2021https://doi.org/10.1161/STROKEAHA.121.035049Stroke. ;0:STROKEAHA.121.035049

Abstract

Recent advancements in computed tomography technology, including improved brain coverage and automated processing of the perfusion data, have reinforced the use of perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. The DAWN (Diffusion Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trials have established the benefit of endovascular thrombectomy in patients with acute ischemic stroke with anterior circulation large vessel occlusion up to 24 hours of last seen normal, using perfusion imaging-based patient selection. The compelling data has prompted stroke centers to increasingly introduce automated perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. We present a comprehensive overview of the acquisition and interpretation of automated perfusion imaging in patients with acute ischemic stroke with a special emphasis on the interpretation pearls, pitfalls, and stroke mimicking conditions.

Footnotes

For Sources of Funding and Disclosures, see page xxx.

Correspondence to: Manal Nicolas-Jilwan, MD, Department of Radiology (MBC-28), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia 11211. Email manaljilwan@hotmail.com

CT Perfusion Ischaemic Core Measures Linked to Endovascular Outcome After Stroke

So you described something, WHAT THE HELL USE IS IT OF GETTING 100% RECOVERED?

CT Perfusion Ischaemic Core Measures Linked to Endovascular Outcome After Stroke

By Nancy Melville

YORK, Me -- March 18, 2021 -- Measures of ischaemic core volume detected on computed tomography perfusion (CTP) are significantly associated with outcomes following endovascular treatment of ischaemic stroke, according to a study presented at the 2021 Virtual International Stroke Conference (ISC).

“We found that larger CTP ischaemic core volume was associated with an increased likelihood of achieving poor outcome in current clinical practice,” said Jan W. Hoving, MD, Amsterdam UMC, Amsterdam, the Netherlands.

Emergency endovascular treatment of ischaemic strokes can provide improved outcomes and reduced disability following the stroke when provided up to 24 hours after stroke onset; however, a significant proportion of patients have poor outcomes and mortality, despite the treatment, within 3 months of the stroke.

Imaging techniques that can benefit decision-making for treatment selection among those patients include CTP measures of ischemic core volume, non-contrast CT for scoring of Alberta stroke program early CT score (ASPECTS), and CT angiography to determine the collateral status or assess the occlusion location.

For the current study, the researchers evaluated data from 201 patients who were enrolled in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), and who had received CTP between July 2016 and November 2017.

The patients had a baseline median National Institutes of Health Stroke Scale (NIHSS) score of 16 (interquartile range [IQR], 12-20), and their characteristics were similar to those in the overall MR CLEAN cohort.

The median CTP-calculated ischaemic core volume among the patients was 13.3 (IQR, 5.3-40.9) mL, and their median onset-to-groin time was 153 minutes. Successful reperfusion was achieved in 71% of patients, while 19% of patients were deceased at 90 days.

After adjustment for variables including age, sex, NIHSS, prestrike modified Rankin Scale (mRS), intravenous alteplase, onset-to-groin time, and occlusion site, the median CTP ischaemic core volume was associated with a poor outcome, defined as a 90-day modified Rankin Scale (mRS) score of 5 to 6 (adjusted odds ratio [aOR] = 1.03 per 10 mL; P = .004).
Median CTP ischaemic core volume was associated with good outcomes, defined as an mRS score of 0 to 2 (aOR = 0.98; P = .01). The ischaemic core volume was also associated with a shift on the mRS towards an improved outcome, defined as a shift of ≥1 point (aOR = 0.83 per 10 mL; P< .001).

The ASPECTS and CTA collateral scores were meanwhile not significantly associated with any of the 3 outcomes.

“The findings show that with increasing CTP ischaemic core volumes, the probability of achieving poor outcomes also increases,” said Dr. Hoving. “Moreover, we could not establish a statistically significant association between ASPECTS or CTA collateral score and poor outcome. CTP ischaemic core volume can play a role in identifying patients who are likely to have good outcomes after endovascular therapy.”

ISC is sponsored by the American Heart Association and the American Stroke Association.

[Presentation title: CT Perfusion-Guided Patient Selection for Endovascular Treatment of Acute Ischemic Stroke: Results From the MR CLEAN Registry. Abstract LB14]

Dynamic CTA-Derived Perfusion Maps Predict Final Infarct Volume: The Simple Perfusion Reconstruction Algorithm

Great, your next step is to take these objective maps and create protocols that recover from such damage. I don't care that that is a BHAG(Big Hairy Audacious Goals, but leaders tackle such goals. Are you leaders or mice? I already know there are no leaders in our fucking failures of stroke associations.

The latest here:

Dynamic CTA-Derived Perfusion Maps Predict Final Infarct Volume: The Simple Perfusion Reconstruction Algorithm

C.C. McDougall, L. Chan, S. Sachan, J. Guo, R.G. Sah, B.K. Menon, A.M. Demchuk, M.D. Hill, N.D. Forkert, C.D. d’Esterre and P.A. Barber

American Journal of Neuroradiology October 2020, DOI: https://doi.org/10.3174/ajnr.A6783

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Abstract

BACKGROUND AND PURPOSE: Infarct core volume measurement using CTP (CT perfusion) is a mainstay paradigm for stroke treatment decision-making. Yet, there are several downfalls with cine CTP technology that can be overcome by adopting the simple perfusion reconstruction algorithm (SPIRAL) derived from multiphase CTA. We compare SPIRAL with CTP parameters for the prediction of 24-hour infarction.

MATERIALS AND METHODS: Seventy-two patients had admission NCCT, multiphase CTA, CTP, and 24-hour DWI. All patients had successful/quality reperfusion. Patient-level and cohort-level receiver operator characteristic curves were generated to determine accuracy. A 10-fold cross-validation was performed on the cohort-level data. Infarct core volume was compared for SPIRAL, CTP–time-to-maximum, and final DWI by Bland-Altman analysis.

RESULTS: When we compared the accuracy in patients with early and late reperfusion for cortical GM and WM, there was no significant difference at the patient level (0.83 versus 0.84, respectively), cohort level (0.82 versus 0.81, respectively), or the cross-validation (0.77 versus 0.74, respectively). In the patient-level receiver operating characteristic analysis, the SPIRAL map had a slightly higher, though nonsignificant (P < .05), average receiver operating characteristic area under the curve (cortical GM/WM, r = 0.82; basal ganglia  = 0.79, respectively) than both the CTP–time-to-maximum (cortical GM/WM = 0.82; basal ganglia = 0.78, respectively) and CTP-CBF (cortical GM/WM = 0.74; basal ganglia = 0.78, respectively) parameter maps. The same relationship was observed at the cohort level. The Bland-Altman plot limits of agreement for SPIRAL and time-to-maximum infarct volume were similar compared with 24-hour DWI.

CONCLUSIONS: We have shown that perfusion maps generated from a temporally sampled helical CTA are an accurate surrogate for infarct core.

 

Incremental Value of Computed Tomography Perfusion for Final Infarct Prediction in Acute Ischemic Cerebellar Stroke

Will you stop the prognostic crapola. Survivors want protocols that deliver 100% recovery, NOT this crap. 

Incremental Value of Computed Tomography Perfusion for Final Infarct Prediction in Acute Ischemic Cerebellar Stroke

Fabritius MP¹, Reidler P¹, Froelich MF¹, Rotkopf LT¹, Liebig T², Kellert L^3,4, Feil K^3,5, Tiedt S⁶, Kazmierczak PM¹, Thierfelder KM⁷, Puhr-Westerheide D¹, Kunz WG¹.

Author information

1

Department ot Radiology University Hospital, LMU Munich Munich Germany.

2

Department of Neuroradiology University Hospital LMU Munich Germany.

3

Department of Neurology University Hospital LMU Munich Germany.

4

Department of Neurology University Hospital Heidelberg Germany.

5

German Center for Vertigo and Balance Disorders University Hospital LMU Munich Germany.

6

Institute for Stroke and Dementia Research University Hospital LMU Munich Germany.

7

Institute of Diagnostic and Interventional Radiology Pediatric Radiology and Neuroradiology University Medical Center Rostock Germany.

Abstract

Background 
The diagnosis of ischemic cerebellar stroke is challenging because of nonspecific symptoms and very limited accuracy of commonly applied computed tomography (CT) imaging. Advances in CT perfusion imaging provide increasing value in the detection of posterior circulation stroke, but the prognostic value remains unclear. We aimed to identify imaging parameters that predict morphologic outcome in cerebellar stroke patients using advanced CT including whole-brain CT perfusion (WB-CTP).
Methods and Results 
We selected all subjects with cerebellar WB-CTP perfusion deficits and follow-up-confirmed cerebellar infarction from a consecutive cohort with suspected stroke who underwent WB-CTP. Posterior-circulation-Acute-Stroke-Prognosis-Early-CT-Score (pc-ASPECTS) was determined on noncontrast CT, CT angiography source images, and on parametric WB-CTP maps. Cerebellar perfusion deficit volumes on all maps and the final infarction volume on follow-up imaging were quantified. Uni- and multivariate regression analyses were performed. Sixty patients fulfilled the inclusion criteria. pc-ASPECTS on CT angiography source images (ß, -9.239; 95% CI, -14.220 to -4.259; P<0.001) and cerebral blood flow deficit volume (ß, 0.886; 95% CI, 0.684 to 1.089; P<0.001) were significantly associated with final infarction volume in univariate linear regression analysis. The association of cerebral blood flow deficit volume (ß, 0.830; 95% CI, 0.605-1.055; P<0.001) was confirmed in a multivariate linear regression model adjusted for age, sex, pc-ASPECTS on noncontrast CT, and CT angiography source images and the National Institutes of Health Stroke Scale score on admission. No other clinical or imaging parameters were associated with cerebellar stroke final infarction volume (P>0.05).
Conclusions 
In contrast to noncontrast CT and CT angiography, WB-CTP imaging contains prognostic information for morphologic outcome in patients with acute cerebellar stroke.

KEYWORDS:

CT perfusion imaging; ischemic stroke; perfusion imaging; posterior circulation

PMID:

31631729

DOI:

10.1161/JAHA.119.013069

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Cerebral perfusion and its relationship to post-concussion syndrome in mild traumatic brain injury: a prospective controlled cohort study

We will never know if this could help survivors since there is no followup to any research that might help survivors. I lay that failure at the feet of our fucking failures of stroke associations. 

Cerebral perfusion and its relationship to post-concussion syndrome in mild traumatic brain injury: a prospective controlled cohort study

 

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CACN Chair’s Select Abstracts

A.03 Cerebral perfusion and its relationship to post-concussion syndrome in mild traumatic brain injury: a prospective controlled cohort study

KM Barlow^a1, LD Marcil^a1, D Dewey^a1, H Carlson^a1, FP MacMaster^a1, BL Brooks^a1 and RM Lebel^a1

^a1 (Calgary)

Abstract

Background: Persistent post-concussive symptoms (PCS) have been linked to increased cortical network activation and decreased cerebrovascular reactivity. Decreased cerebral perfusion could help explain PCS and may be a biomarker to track recovery.  
Methods: Children (ages 8 to 18 years) symptomatic with PCS at one month post-injury were studied. Children who recovered following a mTBI (asymptomatic group) and healthy children acted as controls. Pseudocontinuous arterial spin labeling MRI was used to quantify cerebral blood flow (CBF). All subjects were imaged at approximately 40 days post-injury. Symptomatic group underwent repeat neuroimaging 4-5 weeks later.  
Results: Seventy-two participants (14.1 years; 95% CIs: 13.5, 14.8) underwent neuroimaging at 40 days post-injury. Global CBF was significantly higher in the symptomatic group compared to healthy controls, and lower in the asymptomatic group (F(2,57) 9.734 p<0.001). Symptomatic children had increased CBF in the frontal and occipital regions, and asymptomatic children had decreased CBF in the temporal regions compared to healthy controls. CBF decreased in symptomatic children over time. CBF was a predictor of cognition (R²=0.235;p=0.001).
Conclusions: Cerebral perfusion is altered in children with mTBI and is associated with recovery trajectory. Asymptomatic children had decreased CBF suggesting cerebral recovery is ongoing. Further longitudinal studies are required to determine if these perfusion patterns continue to change over time.

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Brain reorganization after endovascular treatment in a patient with a large arteriovenous malformation: the role of diagnostic and functional neuroimaging techniques

No clue what this means, that is what your non functional doctor is for.
http://www.ncbi.nlm.nih.gov/pubmed/24070082

La Piana R, Bourassa-Blanchette S, Klein D, Mok K, Del Pilar Cortes Nino M, Tampieri D.

Source

Department of Neuroradiology, Montreal Neurological Institute and Hospital, McGill University; Montreal, Canada - E-mail: donatella.tampieri@mcgill.ca.

Abstract

We describe a case of brain cortical reorganization after embolization of a large right temporal arteriovenous malformation. A comprehensive imaging protocol, including functional magnetic resonance imaging (fMRI), cortical thickness analysis and 320-row computed tomography (CT) perfusion was used to provide information on brain plasticity and potential steal phenomenon. A 25-year-old man known for a right temporal grade V Spetzler-Martin classification arteriovenous malformation (AVM) presented with left progressive hemiparesis. He underwent functional 3T magnetic resonance imaging (fMRI), cortical thickness analysis, and CT perfusion (CT 320 row, Aquilion ONE, Toshiba, Tokyo, Japan) before and after endovascular treatment.

The results were compared to look for modifications in brain perfusion and organization. An improvement in the left hemiparesis and a reorganization of motor function were observed after endovascular treatment. Modifications in the angioarchitecture and perfusion of an extensive AVM may be accompanied by a functional and structural reorganization of the brain. The location in the so-called eloquent regions may not be sufficient to explain the wide spectrum of symptoms that these patients can present. A more comprehensive approach considering a global involvement of the brain in patients with large AVMs is suggested to achieve the best treatment strategy and to stage treatment in incurable AVMs.

Whole-brain cerebral blood flow mapping using 3D echo planar imaging and pulsed arterial tagging

And what is your doctor doing with this to identify damage in penumbra areas that can be saved? What saving neuron solutions are being used? You mean there are none? 
Another article at the bottom.
http://www.ncbi.nlm.nih.gov/pubmed/21274969

Abstract

PURPOSE:

To quantitate cerebral blood flow (CBF) in the entire brain using the 3D echo planar imaging (EPI) PULSAR (pulsed star labeling) technique.

MATERIALS AND METHODS:

The PULSAR technique was modified to 1) incorporate a nonselective inversion pulse to suppress background signal; 2) to use 3D EPI acquisition; and 3) to modulate flip angle in such a manner as to minimize the blurring resulting from T1 modulation along the slice encoding direction. Computation of CBF was performed using the general kinetic model (GKM). In a series of healthy volunteers (n = 12), we first investigated the effects of introducing an inversion pulse on the measured value of CBF and on the temporal stability of the perfusion signal. Next we investigated the effect of flip angle modulation on the spatial blurring of the perfusion signal. Finally, we evaluated the repeatability of the CBF measurements, including the influence of the measurement of arterial blood magnetization (a calibration factor for the GKM).

RESULTS:

The sequence provides sufficient perfusion signal to achieve whole brain coverage in ≈ 5 minutes. Introduction of the inversion pulse for background suppression did not significantly affect computed CBF values, but did reduce the fluctuation in the perfusion signal. Flip angle modulation reduced blurring, resulting in higher estimates of gray matter (GM) CBF and lower estimates of white matter (WM) CBF. The repeatability study showed that measurement of arterial blood signal did not result in significantly higher error in the perfusion measurement.

CONCLUSION:

Improvements in acquisition and sequence preparation presented here allow for better quantification and localization of perfusion signal, allowing for accurate whole-brain CBF measurements in 5 minutes.
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Cerebral blood flow measured with 3D pseudocontinuous arterial spin-labeling MR imaging in Alzheimer disease and mild cognitive impairment: a marker for disease severity

Is cerebral oxygenation negatively affected by infusion of norepinephrine in healthy subjects?

If all the HBOT pushers are correct in that extra oxygenation will help save neurons then this method would be lots easier and cheaper. Your doctor should know the answer, its only been published 4 years ago.  You do think your doctor is less than 4 years out-of-date? Don't you?
http://bja.oxfordjournals.org/content/102/6/800

Abstract

Background Vasopressor agents are commonly used to increase mean arterial pressure (MAP) in order to secure a pressure gradient to perfuse vital organs. The influence of norepinephrine on cerebral oxygenation is not clear. The aim of this study was to evaluate the impact of the infusion of norepinephrine on cerebral oxygenation in healthy subjects.

Methods Three doses of norepinephrine (0.05, 0.1, and 0.15 µg kg⁻¹ min⁻¹ for 20 min each) were infused in nine healthy subjects [six males; 26 (6) yr, mean (sd)]. MAP, cerebral oxygenation characterized by frontal lobe oxygenation (Sc_o2) and internal jugular venous oxygen saturation (Sjv_o2), middle cerebral artery mean flow velocity (MCA Vmean), cardiac output (CO), and arterial partial pressure for carbon dioxide (Pa_co2) were evaluated.

Results MAP increased from 88 (79–101) [median (range)] to 115 (98–128) mm Hg with increasing doses of norepinephrine (P < 0.05), reflecting an increase in total peripheral resistance [20.3 (12.2–25.8) to 25.2 (16.4–28.5) mm Hg min litre⁻¹; P < 0.05] since CO remained at baseline values. Sc_o2 and Sjv_o2 decreased with increasing doses of norepinephrine, reaching statistical significance with norepinephrine infused at 0.1 µg kg⁻¹ min⁻¹ [Sc_o2: 78 (75–94) to 69 (61–83)%; P < 0.05; Sjv_o2: 67 (8) to 64 (7)%; P < 0.01]. MCA Vmean was reduced with each dose of norepinephrine [56.9 (11.2) to 55.0 (11.7) cm s⁻¹; P < 0.05] and Pa_co2 lowered from 5.4 (0.4) to 5.1 (0.4) kPa (P < 0.001).

Conclusions This study suggests that infusion of norepinephrine at 0.1 µg kg⁻¹ min⁻¹ or higher may negatively affect cerebral oxygenation.

Electrochemical Failure of the Brain Cortex Is More Deleterious When it Is Accompanied by Low Perfusion

See if your doctor has the same understanding of depolarization and commitment point
http://stroke.ahajournals.org/content/early/2013/01/03/STROKEAHA.112.660589.short

Abstract

Background and Purpose—Clinical and experimental evidence suggests that spreading depolarization facilitates neuronal injury when its duration exceeds a certain time point, termed commitment point. We here investigated whether this commitment point is shifted to an earlier period, when spreading depolarization is accompanied by a perfusion deficit.

Methods—Electrophysiological and cerebral blood flow changes were studied in a rat cranial window model followed by histological and immunohistochemical analyses of cortical damage.

Results—In group 1, brain topical application of artificial cerebrospinal fluid (ACSF) with high K⁺ concentration ([K⁺]_ACSF) for 1 hour allowed us to induce a depolarizing event of fixed duration with cerebral blood flow fluctuations around the baseline (short-lasting initial hypoperfusions followed by hyperemia). In group 2, coapplication of the NO-scavenger hemoglobin ([Hb]_ACSF) with high [K⁺]_ACSF caused a depolarizing event of similar duration, to which a severe perfusion deficit was coupled (=spreading ischemia). In group 3, intravenous coadministration of the L-type calcium channel antagonist nimodipine with brain topical application of high [K⁺]_ACSF/[Hb]_ACSF caused spreading ischemia to revert to spreading hyperemia. Whereas scattered neuronal injury occurred in the superficial cortical layers in the window areas of groups 1 and 3, necrosis of all layers with partial loss of the tissue texture and microglial activation were observed in group 2.

Conclusions—The results suggest that electrochemical failure of the cortex is more deleterious when it is accompanied by low perfusion. Thus, the commitment point of the cortex is not a universal value but depends on additional factors, such as the level of perfusion.

Efficacy of super-pulsed 905 nm Low Level Laser Therapy (LLLT) in the management of Traumatic Brain Injury (TBI): A case study

Ask your doctor exactly how this is provided to patients and where you rent a home version.
http://scholar.google.com/scholar_url?hl=en&q=http://www.scirp.org/journal/PaperDownload.aspx%3FpaperID%3D24793&sa=X&scisig=AAGBfm3CgtJiTfyI7ht8-zY2j32CMf-mIA&oi=scholaralrt
ABSTRACT
Traumatic brain injury is a major health concern worldwide with massive financial and social impact. Conventional treatments primarily focus on the prevention of further damage to the brain parenchyma, while failing to address the already existent symptoms. Previous clinical studies have shown that Low Level Laser Therapy (LLLT) can significantly reduce pain and induce temporary vasodilation in capillaries, which the authors hypothesize can be used to improve the quality of life in TBI patients by treating their current symptoms, which are predominately migraine- like headaches. This case report illustrates the use of LLLT in the treatment of a patient with a TBI and the great clinical success achieved in the reduction of pain, as measured by VAS—achievable within five treatments of 10 minutes in duration.
1. INTRODUCTION
Traumatic brain injury (TBI) typically occurs when there is any sudden trauma to the skull that induces damage to the brain. There are many causes of TBIs, but unfortunately no documented cures. According to Faul et al., the annual incidence of TBI in the United States is approxi- mately 1.7 million incidents, which account for 30.5% of injury related deaths [1]. The direct and indirect costs of TBI totaled an estimated 76.5 billion dollars in the United States in 2000 [2]. Traumatic brain injuries play a major role in the health care of our nation, especially in our armed forces, where the men and women serving our country are at a higher risk to suffer a TBI.
Treatment is centered on preventing future insult to the brain, but very little can be done to treat the already existing symptoms. These symptoms, as described by the National Institutes of Health, range from mild to severe and include: headaches, nausea, vomiting, confusion, and blurry vision. Current theory on alleviating the symp- toms of TBIs is based on reducing inflammatory and oxi- dative stress and increasing perfusion to support meta- bolic needs [3]. A study by Naeser et al. looked at the use of Near Infra Red (NIR) light for the treatment of TBI, stroke, and neurodegenerative disease. Their results were very promising, showing that nightly treatments with NIR LED over a period of months to years improved cognitive abilities [4]. Furthermore, they showed that the use of NIR light increased ATP production, caused vaso- dilation, and improved perfusion. We believe that the superpulsed 905 nm LLLT system employed in this case study operates through similar mechanisms of action and to support our hypothesis we present a case report of a patient with a traumatic brain injury that was treated with the superpulsed 905 nm LLLT system two years after the injury occurred.

Statins and cerebral perfusion in patients with leukoaraiosis–a translational proof‐of‐principal MRI study

No abstract available so your doctor will need to buy the article.
http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2012.00807.x/abstract
Statins and cerebral perfusion in patients with
leukoaraiosis–a translational proof-of-principal MRI study.

B-cell Lymphoma-2 (Bcl-2) is an Essential Regulator of Adult Hippocampal Neurogenesis

Get your researcher involved to increase the number of surviving neurogenesis neurons. Another good dissertation. Only 89 pages.
http://www.ruor.uottawa.ca/fr/bitstream/handle/10393/23287/Ceizar_Maheen_2012_thesis.pdf?sequence=3
ABSTRACT
Of the thousands of dividing progenitor cells (PCs) generated daily in the adult
brain only a very small proportion survive to become mature neurons through the
process of neurogenesis. Identification of the mechanisms that regulate cell
death associated with neurogenesis would aid in harnessing the potential
therapeutic value of PCs. Apoptosis, or programmed cell death, is suggested to
regulate death of PCs in the adult brain as overexpression of B-cell lymphoma 2
(Bcl-2), an anti-apoptotic protein, enhances the survival of new neurons. To
directly assess if Bcl-2 is a regulator of apoptosis in PCs, this study examined the
outcome of removal of Bcl-2 from the developing PCs in the adult mouse brain.
Retroviral mediated gene transfer of Cre into adult floxed Bcl-2 mice eliminated
Bcl-2 from developing PCs and resulted in the complete absence of new neurons
at 30 days post viral injection. Similarly, Bcl-2 removal through the use of nestininduced
conditional knockout mice resulted in reduced number of mature
neurons. The function of Bcl-2 in the PCs was also dependent on Bcl-2-
associated X (BAX) protein, as demonstrated by an increase in new neurons
formed following viral-mediated removal of Bcl-2 in BAX knockout mice. Together
these findings demonstrate that Bcl-2 is an essential regulator of neurogenesis in
the adult hippocampus.

Authorizations .............................................................................................. i
Abstract........................................................................................................ xi
List of Tables ............................................................................................... xiv
List of Figures .............................................................................................. xv
List of Abbreviations..................................................................................... xvii
Acknowledgements...................................................................................... xx
Chapter 1: Introduction ............................................................................ 1
1.1 ..Adult Neurogenesis ........................................................................ 1
1.2 Progenitor Cell (PC) Development in the Hippocampus................. 2
1.3 Cell Death Occurring During Adult Neurogenesis........................... 7
1.4 Apoptosis ....................................................................................... 9
1.5 The Intrinsic Apoptotic Pathway ..................................................... 12
1.6 Players Involved with Apoptosis in Adult Neurogenesis ................. 15
Objectives and Statement of Hypothesis ................................................ 18
Chapter 2: Materials and Methods ........................................................... 19
2.1 Animals .......................................................................................... 19
2.2 Genotyping .................................................................................... 19
2.3 Retroviral Vectors & Injections ....................................................... 20
2.4 Tamoxifen Treatments ................................................................... 22
2.5 Perfusion and Tissue Collection .................................................... 23
2.6 Immunohistochemistry.................................................................... 23
2.7 Quantification Using Microscopy ................................................... 26
2.8 Statistical Analysis ......................................................................... 27
Chapter 3: Results
3.1 Retroviral-Mediated Removal of Bcl-2 Prevents the
Survival of Newborn Mature Neurons ............................................ 28
3.2 Bcl-2 Functions in the Adult Hippocampus in a BAX
xiii
Dependent Manner ........................................................................ 33
3.3 Generation of the Inducible Triple Transgenic Bcl-2
Knockout Mouse ............................................................................ 35
3.4 Removal of Bcl-2 in Nestin-Expressing Cells and their
Progeny Reduces the Recombined, Stem and Immature
Neurons at 12 days ....................................................................... 37
3.5 Removal of Bcl-2 in Nestin-Expressing Cells and Their
Progeny Altered the Mature Neuron Population 30
Days After Removal ....................................................................... 45
Chapter 4: Discussion .............................................................................. 51
4.1 Bcl-2 has a Cell-Autonomous Essential Role in
Adult Neurogenesis ........................................................................ 51
4.2 Bcl-2-Mediated Effects on the Stem-cell Like
Population ...................................................................................... 53
4.3 Differences in Neurogenesis between Floxed
Bcl-2 Mice Infected with Retroviral Cre and
nBcl-2 KO Mice............................................................................... 55
4.4 The Expression of Bcl-2 During Adult Neurogenesis .................... 56
4.5 The Role of Bcl-2 in Regulating Apoptosis in
Adult Neurogenesis ........................................................................ 56
References ................................................................................................. 59

Perfusion Augmentation in Acute Stroke Using Mechanical Counter-Pulsation–Phase IIa

I wonder if this got farther, ask your doctor, you may need it for your next stroke. Have them compare it to leg compressions.
http://stroke.ahajournals.org/content/39/10/2760.short

Abstract

Background and Purpose— External counterpulsation (ECP) improves coronary perfusion, increases left ventricular stroke volume similar to intraaortic balloon counterpulsation, and recruits arterial collaterals within ischemic territories. We sought to determine ECPs effect on middle cerebral artery (MCA) blood flow augmentation in normal controls as a first step to support future clinical trials in acute stroke.

Methods— Healthy volunteers were recruited and screened for exclusions. Bilateral 2-MHz pulsed wave transcranial Doppler (TCD) probes were mounted by head frame, and baseline M1 MCA TCD measurements were obtained. ECP was then initiated using standard procedures for 30 minutes, and TCD readings were repeated at 5 and 20 minutes. Physiological correlates associated with ECP-TCD waveform morphology were identified, and measurable criteria for TCD assessment of ECP arterial mean flow velocity (MFV) augmentation were constructed.

Results— Five subjects were enrolled in the study. Preprocedural M1 MCA TCD measurements were within normal limits. Onset of ECP counterpulsation produced an immediate change in TCD waveform configuration with the appearance of a second upstroke at the dicrotic notch, labeled peak diastolic augmented velocity (PDAV). Although end-diastolic velocities did not increase, both R-MCA and L-MCA PDAVs were significantly higher than baseline end-diastolic values (P less than 0.05 Wilcoxon rank-sum test) at 5 and 20 minutes. Augmented MFVs (aMFVs) were also significantly higher than baseline MFV in the R-MCA and L-MCA at both 5 and 20 minutes (P less than 0.05).

Conclusions— ECP induces marked changes in cerebral arterial waveforms and augmented peak diastolic and mean MCA flow velocities on TCD in 5 healthy subjects.