Mechanisms of Brain Injury after Global Cerebral Ischemia

Harukuni, Izumi; Bhardwaj, Anish

doi:10.1016/j.ncl.2005.10.004

Cited by 265 publications

(185 citation statements)

References 121 publications

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“…However, the pathogenesis of LCD remains obscure although it is considered an adrenal dysfunction because volume expanders and inotropic agents are ineffective whereas intravenous steroids are significantly effective in most cases. Brain injury in cerebral ischemia is currently thought to consist of apoptosis, excitotoxicity (e.g., glutamate and aspartate) and inflammation (Harukuni and Bhardwaj 2006). Besides damage to the cerebral white matter as a direct consequence of remarkable hypotension, other unknown factors might cause severe PVL during LCD.…”

Section: Discussionmentioning

confidence: 99%

Periventricular Leukomalacia with Late-Onset Circulatory Dysfunction of Premature Infants: Correlation with Severity of Magnetic Resonance Imaging Findings and Neurological Outcomes

Kobayashi

Fujimoto

Fukuda

et al. 2006

Tohoku J. Exp. Med.

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The incidence of late-onset circulatory dysfunction (LCD) of premature infants, which is characterized by sudden hypotension and oliguria, has recently increased in Japan. This condition suddenly occurs after several days of age without obvious causes in preterm infants with stable respiration and circulation. Intravenous steroids frequently improve the hypotension. The main problem with LCD is the subsequent and frequent onset of periventricular leukomalacia (PVL), and neurological development appears to be worse in PVL patients with LCD than those without LCD. The aim of this study was to determine whether the severity of magnetic resonance imaging (MRI) findings and neurological outcomes differ between infants who developed PVL after LCD and those who developed PVL without LCD. We retrospectively studied preterm infants who were delivered at less than 33 weeks of gestation between the years 2000 and 2003. During the study period, 10 and 26 infants developed PVL with and without LCD, respectively. The incidence of severe or moderate MRI findings was significantly higher in PVL patients with LCD (100%) than those without LCD (50%; p < 0.05). The incidence of severe cerebral palsy was 88% in PVL infants with LCD and 43% in PVL infants without LCD ( p < 0.05). Moreover, the incidence of visual disorders was significantly higher in PVL infants with LCD (63%) than those without LCD (9%; p < 0.01). In conclusion,

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Section: Discussionmentioning

confidence: 99%

Periventricular Leukomalacia with Late-Onset Circulatory Dysfunction of Premature Infants: Correlation with Severity of Magnetic Resonance Imaging Findings and Neurological Outcomes

Kobayashi

Fujimoto

Fukuda

et al. 2006

Tohoku J. Exp. Med.

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“…Anoxic or ischemic injury after cardiopulmonary arrest can initiate neuronal death and lead to terminal brain stem dysfunction. [13][14][15][16] Progression of injury and neurological decline after nonsurvivable traumatic brain injury or catastrophic brain hemorrhage generally follows a rostral to caudal path over various intervals but has the same final destination. In patients with rapid progression of brain edema and corresponding elevations in intracranial pressure (ICP), the cerebral cortex is compressed against the inner surface of the skull.…”

Section: Pathophysiology Of Brain Injurymentioning

confidence: 99%

Brain Death: Assessment, Controversy, and Confounding Factors

Arbour

2013

Critical Care Nurse

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When brain injury is refractory to aggressive management and is considered nonsurvivable, with loss of consciousness and brain stem reflexes, a brain death protocol may be initiated to determine death according to neurological criteria. Clinical evaluation typically entails 2 consecutive formal neurological examinations to document total loss of consciousness and absence of brain stem reflexes and then apnea testing to evaluate carbon dioxide unresponsiveness within the brain stem. Confounding factors such as use of therapeutic hypothermia, high-dose metabolic suppression, and movements associated with complex spinal reflexes, fasciculations, or cardiogenic ventilator autotriggering may delay initiation or completion of brain death protocols. Neurodiagnostic studies such as 4-vessel cerebral angiography can rapidly document absence of blood flow to the brain and decrease intervals between onset of terminal brain stem herniation and formal declaration of death by neurological criteria. Intracranial pathophysiology leading to brain death must be considered along with clinical assessment, patterns of vital signs, and relevant diagnostic studies.

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“…Thus, a shorter duration of ischemia (3-5 min) is responsible for injury to CA1 pyramidal neurons of the hyppocampus, whereas a longer duration (15-20 min) of ischemia induces injury to medium-sized neurons of the striatum. Progression of irreversible neuronal injury after ROSC also has temporal variations, and is observed within 3 hours of estab-lishing recirculation for striatum neurons and within 48-72 hours for CA1 pyramidal neurons [20]. In contrast to the earlier theory that considered energy failure as the main characteristic of ischemia, the active cellular response to the ischemic insult is now recognized as the major process [21].…”

Section: Ischemic Neuronal Injurymentioning

confidence: 99%

“…These are often considered more damaging to the brain than the ischemia itself [12] and they produce additional injury, because the reperfusion leads to secondary brain injury from an influx of neutrophils, an increase of reactive oxygen species (ROS) with damage to intracellular proteins and DNA, and cerebral edema and hemorrhage [20]. The reperfusion injury consists of three molecular phases.…”

Section: Ischemic Cascadementioning

confidence: 99%

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

Miclescu¹

2010

Acta Anaesthesiol Scand

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Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in "the field." Based on findings that MBL cardio-and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available. Keywords: Cardiac arrest, cardiopulmonary resuscitation, reperfusion injury, methylene blue, nitric oxide, nitric oxide synthases, blood-brain barrier

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Mechanisms of Brain Injury after Global Cerebral Ischemia

Cited by 265 publications

References 121 publications

Periventricular Leukomalacia with Late-Onset Circulatory Dysfunction of Premature Infants: Correlation with Severity of Magnetic Resonance Imaging Findings and Neurological Outcomes

Periventricular Leukomalacia with Late-Onset Circulatory Dysfunction of Premature Infants: Correlation with Severity of Magnetic Resonance Imaging Findings and Neurological Outcomes

Brain Death: Assessment, Controversy, and Confounding Factors

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

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