Single photon emission computed tomography imaging of cerebral blood flow, blood–brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats

Garrigue, Philippe; Giacomino, Laura; Bucci, Chiara; Muzio, Valeria; Filannino, Maria A; Sabatier, Florence; Dignat-George, Françoise; Pisano, Pascale; Guillet, Benjamin

doi:10.1177/1747493015607516

Cited by 26 publications

(21 citation statements)

References 32 publications

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“…ECFC are considered to be the relevant endothelial progenitors due to their specific vasculogenic activity [11,12]. We previously showed that intravenous administration of ECFC contributed to vascular recovery, limited tissue injury after hind limb ischemia, and transient cerebral ischemia in adult rodents [14,15,[32][33][34][35]. In all these models, ECFC administration was associated with a decrease in apoptosis, a growth factor release enhancement and a neovascularization stimulation.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Grandvuillemin

Garrigue

Ramdani

et al. 2017

Stem Cells Translational Medicine

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Neonatal hypoxic-ischemic encephalopathy (NHIE) is a dramatic perinatal complication, associated with poor neurological prognosis despite neuroprotection by therapeutic hypothermia, in the absence of an available curative therapy. We evaluated and compared ready-to-use human umbilical cord blood cells (HUCBC) and bankable but allogeneic endothelial progenitors (ECFC) as cell therapy candidate for NHIE. We compared benefits of HUCBC and ECFC transplantation 48 hours after injury in male rat NHIE model, based on the Rice-Vannucci approach. Based on behavioral tests, immune-histological assessment and metabolic imaging of brain perfusion using single photon emission computed tomography (SPECT), HUCBC, or ECFC administration provided equally early and sustained functional benefits, up to 8 weeks after injury. These results were associated with total normalization of injured hemisphere cerebral blood flow assessed by SPECT/CT imaging. In conclusion, even if ECFC represent an efficient candidate, HUCBC autologous criteria and easier availability make them the ideal candidate for hypoxic-ischemic cell therapy. STEM CELLS TRANSLATIONAL MEDICINE 2017;6:1987-1996 SIGNIFICANCE STATEMENTNeonatal hypoxic ischemic encephalopathy is a dramatic perinatal complication. Neurological and neurosensory sequelae are frequent in survivors, including motor or learning disabilities, cerebral palsy, or epilepsy. Facing the absence of effective curative therapy, many hopes have been credited in cell therapy strategies. Based on behavioral tests, immune-histological assessment and metabolic imaging of brain perfusion using single photon emission computed tomography, we report in this work that cell transplantation of both human umbilical cord blood cells and endothelial progenitors provided equally early and sustained functional benefits, up to adulthood.

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Section: Discussionmentioning

confidence: 99%

Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Grandvuillemin

Garrigue

Ramdani

et al. 2017

Stem Cells Translational Medicine

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“…Quantification of isotope entry with SPECT imaging is done voxel by voxel to assess radioactivity concentration (absolute or relative) within varied brain regions. This technique is known to be less sensitive for smaller lesions or less disrupted areas [25–27]. CT has been shown to be more sensitive than SPECT in detecting smaller areas of BBB disruption because SPECT results in low spatial resolution [22].…”

Section: Introductionmentioning

confidence: 99%

The effect of regadenoson on the integrity of the human blood–brain barrier, a pilot study

et al. 2017

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Regadenoson is an FDA approved adenosine receptor agonist which increases blood-brain barrier (BBB) permeability in rodents. Regadenoson is used clinically for pharmacologic cardiac stress testing using SPECT or CT imaging agents that do not cross an intact BBB. This study was conducted to determine if standard doses of regadenoson transiently disrupt the human BBB allowing higher concentrations of systemically administered imaging agents to enter the brain. Patients without known intracranial disease undergoing clinically indicated pharmacologic cardiac stress tests were eligible for this study. They received regadenoson (0.4 mg) followed by brain imaging with either Tc-sestamibi for SPECT or visipaque for CT imaging. Pre- and post-regadenoson penetration of imaging agents into brain were quantified [SPECT: radioactive counts, CT: Hounsfield units (HU)] and compared using a matched-pairs t-test. Twelve patients (33% male, median 60 yo) were accrued: 7 SPECT and 5 CT. No significant differences were noted in pre- and post-regadenoson values using mean radionuclide counts (726 vs. 757) or HU (29 vs. 30). While animal studies have demonstrated that regadenoson transiently increases the permeability of the BBB to dextran and temozolomide, we were unable to document changes in the penetration of contrast agents in humans with intact BBB using the FDA approved doses of regadenoson for cardiac evaluation. Further studies are needed exploring alternate regadenoson dosing, schedules, and studies in patients with brain tumors; as transiently disrupting the BBB to improve drug entry into the brain is critical to improving the care of patients with CNS malignancies.

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“…Increased expression of apoptotic proteins, including phosphorylated (p)-Arabidopsis serine/threonine kinase 1 (ASK1), p-c-Jun N-terminal kinase (JNK), p-p38, cleaved caspase-3 and cytochrome c in the ischemic penumbra has been observed following stroke ( 177 ). Studies have reported that the inhibition of apoptosis may prevent the development of cerebral ischemia/reperfusion injury ( 166 , 180 – 185 ). Thioredoxin-1 (Trx1) small interfering RNA increases ASK1 activation in response to apoptotic stress, Trx1 may therefore be anti-apoptotic and suppress cerebral ischemia/reperfusion injury ( 186 – 188 ), potentially via inhibition of the ASK1-JNK/p38 signaling pathway.…”

Section: Notch Signaling and Apoptosis In Cerebrovascular Diseasesmentioning

confidence: 99%

Notch signaling in cerebrovascular diseases (Review)

Cai

Zhao

Deng

et al. 2016

Molecular Medicine Reports

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The Notch signaling pathway is a crucial regulator of numerous fundamental cellular processes. Increasing evidence suggests that Notch signaling is involved in inflammation and oxidative stress, and thus in the progress of cerebrovascular diseases. In addition, Notch signaling in cerebrovascular diseases is associated with apoptosis, angiogenesis and the function of blood-brain barrier. Despite the contradictory results obtained to date as to whether Notch signaling is harmful or beneficial, the regulation of Notch signaling may provide a novel strategy for the treatment of cerebrovascular diseases.

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Single photon emission computed tomography imaging of cerebral blood flow, blood–brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats

Cited by 26 publications

References 32 publications

Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

The effect of regadenoson on the integrity of the human blood–brain barrier, a pilot study

Notch signaling in cerebrovascular diseases (Review)

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