Cessation Of Cerebral Blood Flow Research Articles

Oxygen imaging of hypoxic pockets in the mouse cerebral cortex.

Consciousness is lost within seconds upon cessation of cerebral blood flow. The brain cannot store oxygen, and interruption of oxidative phosphorylation is fatal within minutes. Yet only rudimentary knowledge exists regarding cortical partial oxygen tension (Po2) dynamics under physiological conditions. Here we introduce Green enhanced Nano-lantern (GeNL), a genetically encoded bioluminescent oxygen indicator for Po2 imaging. In awake behaving mice, we uncover the existence of spontaneous, spatially defined "hypoxic pockets" and demonstrate their linkage to the abrogation of local capillary flow. Exercise reduced the burden of hypoxic pockets by 52% compared with rest. The study provides insight into cortical oxygen dynamics in awake behaving animals and concurrently establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.

Enhanced Interplay of Neuronal Coherence and Coupling in the Dying Human Brain.

The neurophysiological footprint of brain activity after cardiac arrest and during near-death experience (NDE) is not well understood. Although a hypoactive state of brain activity has been assumed, experimental animal studies have shown increased activity after cardiac arrest, particularly in the gamma-band, resulting from hypercapnia prior to and cessation of cerebral blood flow after cardiac arrest. No study has yet investigated this matter in humans. Here, we present continuous electroencephalography (EEG) recording from a dying human brain, obtained from an 87-year-old patient undergoing cardiac arrest after traumatic subdural hematoma. An increase of absolute power in gamma activity in the narrow and broad bands and a decrease in theta power is seen after suppression of bilateral hemispheric responses. After cardiac arrest, delta, beta, alpha and gamma power were decreased but a higher percentage of relative gamma power was observed when compared to the interictal interval. Cross-frequency coupling revealed modulation of left-hemispheric gamma activity by alpha and theta rhythms across all windows, even after cessation of cerebral blood flow. The strongest coupling is observed for narrow- and broad-band gamma activity by the alpha waves during left-sided suppression and after cardiac arrest. Albeit the influence of neuronal injury and swelling, our data provide the first evidence from the dying human brain in a non-experimental, real-life acute care clinical setting and advocate that the human brain may possess the capability to generate coordinated activity during the near-death period.

Usefulness of the optic nerve sheath ultrasound in patients with cessation of cerebral flow.

Establish an association between ONSD and CCBF in neurocritical patients admitted to an ICU. Cross-sectional study of patients admitted in a third level ICU, between April 2017 and April 2018, with neurological pathology. ONSD ultrasound was performed in the first 24hours and as the patient was diagnosed of CCBF. The ONSD values of patients with and without diagnosis of CCBF were compared. 99 patients were included, 29 of whom showed CCBF in transcranial Doppler. The ONSD measurement did not demonstrate significant differences between both groups, 6,59 ± 0,75 in the group with CCBF and 6,39 ± 0,56 in the group without CCBF p=0.141. In our study, ONSD values capable of recognizing CCBF were not identified.

Individualized management objectives for hypoxic-ischemic brain injury after cardiac arrest

Hypoxic-ischemic brain injury after cardiac arrest is the main cause of death and neurologic dysfunction in patients after the return of spontaneous circulation. The mechanisms of ischemic and hypoxic brain injury include hypoxia of brain tissue caused by the cessation of cerebral blood flow during the initial cardiac arrest and cerebrovascular dysfunction and reperfusion injury after the recovery of circulation. Cerebral circulatory perfusion, cerebral autoregulation, and cerebral edema can be monitored and controlled as therapeutic targets. In this study, from the aspects of body temperature, mean arterial pressure, oxygen concentration, partial pressure of carbon dioxide in the artery, and cerebral edema, monitoring methods such as measurement of cerebral oxygen saturation, assessment of cerebral blood flow, imaging of the brain, and measurement of intracranial pressure were introduced to explore individual management objectives for hypoxic-ischemic brain injury.

Impairments of cerebral blood flow microcirculation in rats brought on by cardiac cessation and respiratory arrest.

The impairments of cerebral blood flow microcirculation brought on by cardiac and respiratory arrest were assessed with multi-modal diagnostic facilities, utilising laser speckle contrast imaging, fluorescence spectroscopy and diffuse reflectance spectroscopy. The results of laser speckle contrast imaging show a notable reduction of cerebral blood flow in small and medium size vessels during a few minutes of respiratory arrest, while the same effect was observed in large sinuses and their branches during the circulatory cessation. Concurrently, the redox ratio assessed with fluorescence spectroscopy indicates progressing hypoxia, NADH accumulation and increase of FAD consumption. The results of diffuse reflectance spectra measurements display a more rapid grow of the perfusion of deoxygenated blood in case of circulatory impairment. In addition, consequent histopathological analysis performed by using new tissue staining procedure developed in-house. It shows notably higher reduction of size of the neurons due to their wrinkling within brain tissues influenced by circulation impair. Whereas, the brain tissues altered with the respiratory arrest demonstrate focal perivascular oedema and mild hypoxic changes of neuronal morphology. Thus, the study suggests that consequences of a cessation of cerebral blood flow become more dramatic and dangerous compare to respiratory arrest.

Electrocerebral Signature of Cardiac Death.

Electroencephalography (EEG) findings following cardiovascular collapse in death are uncertain. We aimed to characterize EEG changes immediately preceding and following cardiac death. We retrospectively analyzed EEGs of patients who died from cardiac arrest while undergoing standard EEG monitoring in an intensive care unit. Patients with brain death preceding cardiac death were excluded. Three events during fatal cardiovascular failure were investigated: (1) last recorded QRS complex on electrocardiogram (QRS0), (2) cessation of cerebral blood flow (CBF0) estimated as the time that blood pressure and heart rate dropped below set thresholds, and (3) electrocerebral silence on EEG (EEG0). We evaluated EEG spectral power, coherence, and permutation entropy at these time points. Among 19 patients who died while undergoing EEG monitoring, seven (37%) had a comfort-measures-only status and 18 (95%) had a do-not-resuscitate status in place at the time of death. EEG0 occurred at the time of QRS0 in five patients and after QRS0 in two patients (cohort median - 2.0, interquartile range - 8.0 to 0.0), whereas EEG0 was seen at the time of CBF0 in six patients and following CBF0 in 11 patients (cohort median 2.0min, interquartile range - 1.5 to 6.0). After CBF0, full-spectrum log power (p < 0.001) and coherence (p < 0.001) decreased on EEG, whereas delta (p = 0.007) and theta (p < 0.001) permutation entropy increased. Rarely may patients have transient electrocerebral activity following the last recorded QRS (less than 5min) and estimated cessation of cerebral blood flow. These results may have implications for discussions around cardiopulmonary resuscitation and organ donation.

Usefulness of the optic nerve sheath ultrasound in patients with cessation of cerebral flow

Optic nerve sheath diameter (ONSD) ultrasound has proven to be a useful tool for the detection of intracranial hypertension (IH). The DVNO values, in patients with cessation of cerebral blood flow (CCBF), has not been clarified yet. ObjectiveEstablish an association between DVNO and CFSC in neurocritical patients admitted to an ICU. Patients and methodsCross-sectional study of patients admitted in a third level ICU, between April 2017 and April 2018, with neurological pathology. ONSD ultrasound was performed in the first 24 h and as the patient was diagnosed of CCBF. The ONSD values of patients with and without diagnosis of CCBF were compared. Results99 patients were included, 29 of whom showed CCBF in transcranial Doppler. The ONSD measurement did not demonstrate significant differences between both groups, 65.94 ± 7.55 in the group with CCBF and 63.88 ± 5.56 in the group without CCBF, p = 0.14. ConclusionIn our study, ONSD values capable of recognizing CCBF were not identified.

Syncope in children clinicoetiological correlation

Background: Syncope is the abrupt cessation of cerebral blood flow leading to temporary loss of consciousness. Identification of etiology is utmost important as any syncopal event may be life threatening. Aim was to correlate the clinical and etiological causes of syncope in children and to note their investigational profile.Methods: Among 40 patients presenting with syncope and presyncope were studied. History of the event, precipitating factors were noted. They were investigated with the help of blood pressure, Electrocardiogram (ECG), 2D Echocardiogram and Electroencephalogram (EEG).Results: Out of the 40 patients of syncope 65% were above the age of 10 years with male preponderance (60%). Vasovagal syncope (57%) was the most common cause of syncope followed by orthostatic hypotension (15%), neurological (15%), and cardiac etiology (6%). In the neurological etiology the EEG showed diffuse slow background with occasional sharp bursts in right frontal area in 2 patients while in 4 patients sharp bursts were present in the centero-temporal region. 17% were classified as presyncope, 60% as mild and 22% as having severe syncope. There was a significant correlation of etiology of syncope with duration of hospitalization of more than 4 days and with recurrence of syncope. There was significant correlation of Evaluation of Guidelines in Syncope (EGSYS) score &gt;3 with cardiogenic syncope. On follow up, neurological syncope patients had significant decrease in the number of syncopal episodes as they were immediately started on antiepileptics.Conclusions: Electrocardiogram, 2D Echocardiogram and Electroencephalogram are important tools for the early management and treatment of cardiac and neurological etiology of syncope.

Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation

BackgroundIschemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage.MethodsBy using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO).ResultsSSO significantly reduced the lipopolysaccharide/interferon-γ-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α, and the protein levels of inflammatory enzymes including nitric oxide synthase 2, cyclooxygenase-2 (COX-2), and p38 mitogen-activated protein kinase (MAPK) in microglia, without causing cell toxicity. Although SSO failed to directly alleviate glutamate-induced excitotoxicity in murine cortical neurons, it prevented inflammation-induced neuronal death in microglia-neuron co-cultures. Importantly, oral administration of SSO in Balb/c mice subjected to permanent occlusion of the middle cerebral artery reduced microglial activation in the peri-ischemic area and attenuated brain damage. This in vivo neuroprotective effect of SSO was associated with a reduction in the COX-2 and heme oxygenase-1 immunoreactivities.ConclusionsOur results suggest that SSO is an anti-inflammatory and a possible therapeutic candidate in diseases such as stroke where inflammation is a central hallmark.

An improved three-vessel occlusion model of global cerebral ischemia in rats

We developed an improved three-vessel occlusion model of global cerebral ischemia in rats. This method consists in cessation of cerebral blood flow by accessing a. carotis communis sinistra through the ventral surface of the neck as well as tr. brachiocephalicus and a. subclavia sinistra through the first intercostal space, bypassing the pleural cavity and excluding pneumothorax. After the occlusion of the vessels that resulted in interruption of their blood flow, according to laser-Doppler flowmetry, there was a sharp decline in local cerebral blood flow in the visual cortex to 4±1% of the initial level. After restoring the level of local cerebral blood flow at the 5th minute, 10th minute, 20th minute and 24th hour of reperfusion, the levels of local cerebral blood flow were 51±7%, 41±5%, 35±8% and 54±9% of the initial level, respectively. Histo-quantitative analysis of changes in neurons of the hippocampus of rats showed that after ischemic injury, the numerical density of neurons in hippocampal zone CA1 in the observed 1mm2 region decreased by 29%, 22%, and 35%, respectively, compared to sham-operated animals (p<0.05). By the first day after global cerebral ischemia, the experimental group had shown a mean neurological deficit score equal to 7.5±1.0 and 7.9±0.7 points, followed by a decrease up to score 6.5±1.1 and 5.9±0.7 on the third day, 4.6±0.8 and 4.7±0.5 on the fifth day (on chloral hydrate and propofol anesthesia correspondently).

Astrocytic calcium release mediates peri-infarct depolarizations in a rodent stroke model.

Stroke is one of the most common diseases and a leading cause of death and disability. Cessation of cerebral blood flow (CBF) leads to cell death in the infarct core, but tissue surrounding the core has the potential to recover if local reductions in CBF are restored. In these areas, detrimental peri-infarct depolarizations (PIDs) contribute to secondary infarct growth and negatively affect stroke outcome. However, the cellular pathways underlying PIDs have remained unclear. Here, we have used in vivo multiphoton microscopy, laser speckle imaging of CBF, and electrophysiological recordings in a mouse model of focal ischemia to demonstrate that PIDs are associated with a strong increase of intracellular calcium in astrocytes and neurons. We found that astroglial calcium elevations during PIDs are mediated by inositol triphosphate receptor type 2-dependent (IP3R2-dependent) release from internal stores. Importantly, Ip3r2-deficient mice displayed a reduction of PID frequency and overall PID burden and showed increased neuronal survival after stroke. These effects were not related to local CBF changes in response to PIDs. However, we showed that the release and extracellular accumulation of glutamate during PIDs is strongly curtailed in Ip3r2-deficient mice, resulting in ameliorated calcium overload in neurons and astrocytes. Together, these data implicate astroglial calcium pathways as potential targets for stroke therapy.

Retraction Note: Brain injury following cardiac arrest: pathophysiology for neurocritical care.

[This retracts the article DOI: 10.1186/s40560-016-0140-9.].

Brain injury following cardiac arrest: pathophysiology for neurocritical care.

Cardiac arrest induces the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred to as “reperfusion injury.” Transient brain ischemia following cardiac arrest results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation, and apoptosis. The pathophysiology of post-cardiac arrest brain injury involves a complex cascade of molecular events, most of which remain unknown. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. Mitochondrial dysfunction based on the mitochondrial permeability transition after reperfusion, particularly involving the calcineurin/immunophilin signal transduction pathway, appears to play a pivotal role in the induction of neuronal cell death. The aim of this article is to discuss the underlying pathophysiology of brain damage, which is a devastating pathological condition, and highlight the central signal transduction pathway involved in brain damage, which reveals potential targets for therapeutic intervention.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death

PurposeWe investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). Materials and methodsWe retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. ResultsIntracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (−8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. ConclusionsBrain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow.

Pitfalls in Brain Death Diagnosis: A Case Report

Although there are distinct guidelines in nearly all countries, a reliable secure assessment of brain death in cases with open head injury can be challenging. We present a case of a 32-year-old man with severe head injury after intracranial penetration of a grindstone fragment. As the injury led to destruction of nearly the whole greater wing of the right sphenoid bone and parts of the right orbit, the examination of brainstem reflexes and the confirmation of brain death was unfeasible. On day 2, all clinical criteria of brain death (coma, absence of brainstem reflexes, apnea) were fulfilled. In addition, there was an extinction of brainstem auditory (BAEP) and cerebral (N20) components of median nerve somatosensory evoked potentials, while electroencephalogram (EEG) activity was still present. In the following days, a persisting EEG activity was obtained. Thus, an irreversible loss of whole brain functions could not be proved. As the patient had agreed to organ donation in case of brain death several years ago, ancillary methods to test the cessation of cerebral blood flow were mandatory. However, in this patient these methods turned out either to be doubtful or unavailable. For example, values of transcranial Doppler ultrasonography are not reliable in cases with open head injury. Due to a progressive septic state, time was running out to get the radiopharmaceutical agent for a cerebral scintigraphy (delivery time about 7 days, as the radiopharmaceutical agent was not in stock). Referring to the actual German guidelines, we had no legitimating indication for a cerebral angiography. Finally, the patient died of sepsis. We discuss the widening of the German guidelines in assessing brain death with the fast and low-risk method of cerebral computed tomography-angiography (CTA) to confirm diagnosis of brain death.

Neurosonografie in der neurologischen Notfall- und Intensivmedizin: Monitoring des erhöhten intrakraniellen Druckes, Hirntoddiagnostik und Untersuchung der zerebralen Autoregulation – Teil 2

Transcranial B-mode sonography is an easy to use bedside imaging modality to monitor significant changes of the brain parenchyma such as in malignant middle cerebral infarction or intracerebral hemorrhage. The elevation of intracranial pressure can be followed with various neurosonographical techniques: Measurements of the ventricular width, midline shift, arterial resistance, and optic nerve sheath diameter. They should be viewed as complementary to each other and to other imaging modalities. Repeated cCT and MRI may be avoided in unstable patients by bedside neurosonography in the hands of an experienced physician. Monitoring of evolving hydrocephalus using serial measurements of the third and lateral ventricles can be used to guide therapeutic decisions such as the removal of a ventricular drainage. The cessation of cerebral blood flow in the case of intracranial pressure exceeding systemic arterial pressure is an important part of brain death diagnostics. Early demonstration of a sufficient temporal bone window is needed in patients in whom brain death may be expected. Cerebrovascular autoregulation is an integer component of the brain's blood supply and is compromised in a variety of neurological diseases. In neurological/neurosurgical patients in the intensive care unit, its assessment allows for extended neuromonitoring and control of therapeutic procedures.

Respiratory, Circulatory, and Neurological Responses to Hanging: A Review of Animal Models

The pathophysiology of hanging is still poorly understood. This article presents a review of eight animal models: four models of isolated occlusion of the vessels of the neck (group 1), one model of combined tracheal and vessel occlusion (group 2), and three models of true animal hanging (group 3). Occlusion of the airway passages in group 2 did not accelerate respiratory arrest compared to group 1. Cessation of cerebral blood flow, rather than airway obstruction, seems to be the main cause of respiratory decline. In general, muscular movements ceased after 1-3.5 min and early generalized tonic-clonic convulsions were described. Complete circulatory collapse seems to occur between 4 and 8.5 min. These observations from animal models of hanging are compared with the data collected from filmed human hangings. Avenues to improve animal models are discussed.

Cardiotocographic and Doppler Ultrasonographic Findings in a Fetus with Brain Death Syndrome

The diagnosis of brain death syndrome by cardiotocography (CTG) and Doppler ultrasonography (US) is reported in a fetus at 35 weeks of gestation. A 23-year-old, gravida 2, para 0, woman was referred to our hospital because of the absence of fetal movements. CTG showed fixed fetal heart rate (FHR) pattern. A detailed Doppler US examination of the fetus showed extensive cystic lesions of both cerebral hemispheres, polyhydramnios, total absence of neuromuscular parameters of biophysical profile (BPP) and the cessation of cerebral blood flow. Umbilical cord artery blood gas analysis showed pH 7.3, PaO2 30 mmHg and PaCO2 35 mmHg. A floppy male infant weighing 2,450 g was delivered vaginally at 36 weeks of gestation and the Apgar scores were 1 and 1 at 5 and 10 minutes, respectively. The neonate died 2 days after delivery. Postmortem examination of the brain showed diffuse, anoxic changes with multicystic encephalomalacia in both hemispheres and the brain stem. No other maternal or placental abnormalities were seen. The possibility of intrauterine brain death should be considered in all cases of prolonged fixed FHR pattern, accompanied by absence of neuromuscular parameters of BPP, polyhydramnios and demonstrated cessation of cerebral blood flow by Doppler US. Increased awareness of this event may prevent unnecessary emergency cesarean section.

Distinguishing syncopal from non-syncopal causes of fall in older people

Syncope is the mechanism by which cardiovascular abnor-malities may cause falls in older people. Syncope is a symp-tom, defined as a transient, self-limited loss ofconsciousness, usually leading to falling. The onset of syn-cope is relatively rapid, and the subsequent recovery isspontaneous, complete and usually prompt. The underlyingmechanism is a transient global cerebral hypoperfusion [1,2]. Syncopal loss of consciousness invariably determinesloss of postural tone and, if it occurs in the upright position,falling. Irrespective of the precise underlying cause of syn-cope, a sudden cessation of cerebral blood flow for 6–8 sand/or a decrease in systolic blood pressure to 60 mm Hghas been shown to be sufficient to cause complete loss ofconsciousness. Further, it has been estimated that as little asa 20% drop in cerebral oxygen delivery is sufficient to causeloss of consciousness.Syncope is common amongst older people. In theFramingham study [3], the 10-year cumulative incidence ofsyncope was 6%. The incidence was not, however, con-stant but increased more rapidly from the age of 70 yearsupwards. The 10-year cumulative incidence of syncopewas 11% for both men and women aged 70–79 and 17%and 19% for men and women, respectively, aged 80 orover. The incidence of syncope in an elderly institutional-ised population was 6% per year, with a 10-year prevalenceof 23% and a recurrence rate of 30% [4]. Age-associatedphysiological changes in heart rate, blood pressure, cere-bral blood flow, baroreflex sensitivity and intravascularvolume regulation, combined with comorbid conditionsand concurrent medications, may all contribute to thehigher incidence of syncope in the older population [5].In terms of the immediate injurious consequences ofsyncope, major morbidity such as fractures and motor vehi-cle accidents has been reported in 6% of patients and minorinjury such as laceration and bruises in 29%. Recurrent syn-cope is associated with fractures and soft-tissue injury in12% of patients [6].

The neuropharmacological basis of heat intolerance and its treatment

The heatstroke syndrome is characterized by marked hyperthermia, severe neurological abnormalities, multiple organ dysfunction, endotoxemia, and increased levels of cytokines in the peripheral blood stream. Rodents, when exposed to a high ambient temperature, displayed arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischemia, and cerebral neuronal damage after the onset of heatstroke. Both arterial hypotension and intracranial hypertension result in cessation of cerebral blood flow and lead to oxygen and nutrient deprivation and the initiation of a neurotoxic cascade of secondary mechanisms. The neurotoxic cascade involves overloading of dopamine, serotonin, glutamate, glycerol, nitric oxide, hydroxyl radicals, and/or cytokines. Thus, any measures which are able to restore blood supply and/or intervene the secondary neurotoxic cascades can be used to prevent and/or to treat ischemic neuronal damage in heatstroke.